Neoadjuvant Chemotherapy in early-stage breast cancer: the trend over time and the impact on axillary management, A National Cancer Database Analysis

Neoadjuvant Chemotherapy in early-stage breast cancer: the trend over time and the impact on axillary management, A National Cancer Database Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Neoadjuvant Chemotherapy in early-stage breast cancer: the trend over time and the impact on axillary management, A National Cancer Database Analysis Mahtab Vasigh, David Euhus, Fabian M Johnston, Fasika M Abreha, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6947236/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Despite several benefits to neoadjuvant chemotherapy (NAC), there are uncertainties about NAC utilization in early breast cancer. Methods: We performed a retrospective analysis of the National Cancer Database (NCDB), selecting cN0, cT1-2, M0 breast cancers who received chemotherapy between 2010 and 2021. Axillary lymph node dissection candidacy (ALNDC) was considered positive in the NAC group if any positive nodes were recorded, and in the AC group if more than two positive nodes were documented after surgery. The trend of NAC use and pathologic complete response (pCR) rate over time was assessed. ALNDC was compared between NAC and adjuvant chemotherapy (AC), stratified by stage and phenotype. Results: In a cohort of 295,110 patients, NAC was administered in 13%, increasing from 6% in 2010 to 22% in 2021. While 36% achieved pCR, increasing from 16% in 2010 to 46% in 2021. ALNDC was observed in 9.6% of the NAC and 9.7% of the AC groups (p = 0.2). NAC increased ALNDC in stage I patients (10% vs 8%, p<0.001). However, NAC decreased ALNDC in stage II patients (9% vs. 13%, p < 0.001). NAC increased the rate of ALNDC in hormone-receptor-positive (HR+) (24% vs 13%, p<0.001). However, it decreased ALNDC in HER2+ patients (5% vs 6%, p = 0.004). In the adjusted multivariable analysis, NAC increased the ALNDC (OR: 2.5, 95% CI 2.4-2.6; p < 0.001). Conclusion: Despite the undeniable benefits of NAC, our results revealed an increase in ALNDC in HR+ and stage I breast cancer patients and a decrease in ALNDC in HER2+ patients compared to the AC group. This reinforces the importance of selecting the right treatment for the right patient at the right time. Neoadjuvant chemotherapy Axillary lymph node dissection Early-stage breast cancer Stage I & stage II breast cancer pathologic complete response (pCR) Trend of neoadjuvant chemotherapy over time Figures Figure 1 Figure 2 Figure 3 Synopsis The trend of neoadjuvant chemotherapy utilization in stage I and II breast cancer and its impact on axillary lymph node dissection (ALND) was evaluated. Different indications for ALND in neoadjuvant and adjuvant settings were considered, stratified by phenotype and stage. Introduction Breast cancer is the second most common cancer among women after skin cancer in the United States. Neoadjuvant chemotherapy (NAC) for breast cancer is a well-established therapeutic approach in certain high-risk patients, including those with large tumors or positive lymph nodes. NAC can decrease tumor size in large tumors, making some patients eligible for breast-conserving surgery or downstaging locally advanced and unresectable primary breast cancers to facilitate resection [ 1 , 2 ]. NAC can also eradicate nodal disease in clinically node-positive (cN+) patients, allowing for the avoidance of axillary lymph node dissection (ALND) [ 3 – 5 ]. Since the NSABP B-18 and B-27 clinical trials showed similar outcomes in patients receiving NAC versus AC [ 6 , 7 ], enthusiasm for a neoadjuvant approach in the setting of early-stage breast cancer has intensified, especially in those expected to be excellent responders including the HER2-positive (HER2+) and triple-negative (TN) subtypes [ 8 – 10 ]. NAC can provide an in vivo assessment of tumor response and the invaluable opportunity to deliver targeted therapies in the setting of residual disease [ 6 , 11 – 13 ]. Pivotal clinical trials, such as KATHERINE and CREATE-X, have shown significantly improved survival rates in HER2 + and TNBC patients with residual disease who received adjuvant trastuzumab emtansine (T-DM1) or capecitabine, respectively [ 9 , 10 ]. The benefits of NAC are undeniable, but a potential unintended consequence may be increased utilization of axillary dissection. This is because any nodal disease identified after NAC is recommended for ALND. In contrast, patients not receiving NAC can have up to two positive nodes before receiving the same recommendation [ 14 – 19 ]. ALND is associated with significant risks of neuropathy, lymphedema, and arm dysfunction [ 20 , 21 ]. Early-stage small, node-negative breast tumors have an excellent prognosis under current treatment standards. However, rapid advancements in translational data and systemic therapy options make clinical management more complex. In this study, we evaluated the trend of NAC utilization and pathologic complete response (pCR) over time, and compared the rate of ALNDC between NAC and AC patients in early-stage breast cancers. Methods After Institutional Review Board (IRB) approval, we performed a retrospective analysis of the National Cancer Database (NCDB). The NCDB is a joint collaboration between the American College of Surgeons and the American Cancer Society. Patient-level data are collected from all cancer patients seen at the Commission on Cancer accredited programs, representing approximately 70% of cancer cases in the United States. From the NCDB breast cancer participant user file (PUF), we identified cN0, cT1-2, M0, stage I, and II female breast cancer patients who had primary site surgery and received chemotherapy between 2010–2021. Patients with a history of another malignancy, no axillary surgery, unknown clinical or pathologic nodal status, unknown number of positive nodes, those who received pre-operative endocrine therapy or radiotherapy, unknown breast or axillary surgery, and unknown sequence of chemotherapy compared to surgery were excluded. The complete inclusion and exclusion criteria are outlined in the supplemental material. ALND candidacy (ALNDC) was defined separately for the NAC group compared to the AC group. We abstracted the number of removed nodes and the number of positive nodes on the final pathologic assessment, regardless of the axillary management each case has received (sentinel lymph node biopsy or axillary lymph node dissection). ALNDC was considered positive in the NAC group if any positive nodes were documented during the final pathologic nodal evaluation. However, ALNDC was considered positive in the AC group if more than two positive lymph nodes were documented after axillary surgery. Micrometastasis and isolated tumor cells on final pathology were not considered positive. Patients were categorized into four different phenotype groups: 1- hormone receptor-positive (HR+)/HER2 + as triple positive (TP); 2- HR+/HER2- as HR+; 3- HR-negative (HR-)/HER2 + as HER2+; and 4- HR-/HER2- as triple negative (TN). pCR was defined as ypT0 and ypN0 on the final pathologic report. ypTis was not included in the pCR. We evaluated the Trend of NAC administration and pCR rate between 2010 and 2021. ALNDC was compared between those who received NAC and those who received AC. A subgroup analysis was performed stratified by stage and phenotype. We used descriptive statistics (frequencies, percentages, means, standard deviations) to summarize demographics. Patient and tumor characteristics were compared across subgroups that received NAC and AC, using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. We performed a backward elimination method to select the variables for a multivariable logistic regression model to determine the association between NAC utilization and ALNDC. It was adjusted for the comorbidities (Charlson Comorbidity Index (CCI)), year of diagnosis, stage, lymphovascular invasion (LVI), phenotype, and the type of primary site surgery (mastectomy vs breast-conserving surgery (BCS)). Analysis was performed using Stata software, version 18. Results Comparing the neoadjuvant chemotherapy and adjuvant chemotherapy groups: A total of 295,110 eligible patients were identified from the NCDB (Table 1). The mean age of the patients was 57 ± 12 years; 85% resided in large metropolitan areas, and 64% had private insurance. The patient population consisted of 79% White, 14% African American, and 7% Hispanic individuals. Invasive ductal carcinoma (IDC) constituted 84% of the cases, and 37% of them were grade three. Within this cohort, HER2+ included 7%, TN constituted 28%, and TP and HR+ included 8% and 55%, respectively, and 36% were stage two breast cancers. Of the patients, 42% underwent mastectomy. The mean number of removed nodes was 5.4 ± 5.9, and the mean number of positive nodes was 0.9 ± 2.3. The pN0 was observed in 62% of the AC and 69% of the NAC patients. (Table 1) Compared to AC patients, NAC patients were more likely to be clinical stage II (69% versus 31%, p<0.001), cT2 (71% vs. 35%, p<0.001), TN phenotype (61% vs 23%, p<0.001), and more likely to undergo mastectomy (46% vs 41%, p<0.001). The mean number of removed nodes was 4.1 and 5.6 in the NAC and AC groups, respectively. The mean number of positive nodes was 0.2 and 1 in the NAC and AC groups, respectively. (Table 1) Table 1: Tumor and patient characteristics based on adjuvant or neoadjuvant chemotherapy administration Variables AC N (%) NAC N (%) Total N (%) p 256,795 (87.0) 38,315 (13.0) 295,110 (100) Patients' Characteristics Age at diagnosis (years) 51.5±11.4 55.3±11.1 56.6±12.0 Race White Black Other Unknown 205,413 (80.0) 28,577 (74.6) 233,990 (79.3) <0.001 34,377 (13.4) 6,902 (18.0) 41,279 (14.0) 8,964 (3.5) 1,361 (3.6) 10,325 (3.5) 8,041 (3.1) 1,475 (3.9) 9,516 (3.2) Charlson Comorbidity Index 0 1 2 ≥3 216,836 (84.4) 33,245 (86.8) 250,090 (84.7) <0.001 31,565 (12.3) 3,884 (10.1) 35,449 (12.0) 5,949 (2.3) 794 (2.1) 6,743 (2.3) 2,445 (1.0) 383 (1.0) 2,828 (1.0) Tumor Characteristics Histology Invasive ductal carcinoma Invasive lobular carcinoma Mixed invasive ductal and lobular Other 211,558 (82.4) 35,128 (91.7) 246,686 (83.6) <0.001 18,147 (7.1) 652 (1.7) 18,799 (6.4) 16,314 (6.4) 906 (2.4) 17,220 (5.8) 10,773 (4.2) 1,625 (4.2) 12,398 (4.2) Tumor Grade 1 2 3 Unknown 16,606 (6.5) 642 (1.7) 17,248 (5.8) <0.001 70,657 (27.5) 4,775 (12.5) 75,432 (25.6) 95,224 (37.1) 14,887 (38.9) 110,111 (37.3) 74,308 (28.9) 18,011 (47.0) 92,319 (31.3) Estrogen Receptor Negative Positive Unknown 81,117 (31.6) 29,569 (77.2) 110,686 (37.5) <0.001 174,936 (68.1) 8,611 (22.5) 183,547 (62.2) 742 (0.3) 135 (0.4) 877 (0.3) Progesterone Receptor Negative Positive Unknown 108,533 (42.3) 31,141 (81.3) 139,647 (74.3) <0.001 147,296 (57.4) 7,016 (18.3) 154,312 (52.3) 966 (0.4) 158 (0.4) 1,124 (0.4) Tumor Phenotype Triple Positive Hormone Positive HER2 positive Triple Negative Unknown 20,873 (8.1) 2,533 (6.6) 23,406 (7.9) <0.001 155,605 (60.6) 7,113 (18.6) 162,718 (55.1) 16,314 (6.4) 4,550 (11.9) 20,864 (7.1) 59,414 (23.1) 23,514 (61.4) 82,928 (28.1) 4,589 (1.8) 605 (2.9) 5,194 (1.8) clinical T Stage cT1 cT2 168,131 (65.5) 11123 (29.0) 179,254 (60.7) <0.001 88,664 (34.5) 27,192 (71.0) 115,856 (39.3) Clinical Stage Group 1 2 177,283 (69.0) 12105 (31.6) 189,388 (64.2) <0.001 79,512 (31.0) 26,210 (68.4) 105,722 (35.8) Treatment Type of Surgery Mastectomy Breast-Conserving Surgery 104,796 (40.8) 17,689 (46.2) 122,480 (41.5) <0.001 151,999 (59.2) 20,631 (53.8) 172,630 (58.5) Type of Axillary Surgery ALND SLNB SNLB+ALND No Surgery Unknown 59,249 (29) 138,758 (67.9) 5,571 (2.7) 492 (0.2) 251 (0.1) 7,145 (20.4) 27,163 (77.7) 477 (1.4) 121 (0.4) 53 (0.2) 66,394 (27.8) 165,921 (69.3) 6,048 (2.5) 613 (0.3) 304 (0.1) <0.001 Treatment (Endocrine Therapy) Negative Positive Unknown 92,168 (35.9) 32,453 (84.7) 124,621 (42.2) <0.001 160,441 (62.5) 5,122 (13.4) 165,563 (56.1) 4,186 (1.6) 740 (1.9) 4926 (1.7) Anti HER2 Therapy (2013+) HER2+ Positive Negative TP Positive Negative 3,588 (93.7) 235 (6.1) 1958 (62.4) 1154 (36.8) 1530 (88.4) 197 (11.4) 711 (73.4) 252 (26.0) 5,118 (92.1) 432 (7.8) 2,669 (65.0) 1,406 (34.2) Pathologic Outcomes Number of regional lymph nodes examined 5.54±6.09 4.07±4.06 5.35±5.89 number of regional lymph nodes positive 0.95±2.39 0.22±1.09 0.85±2.27 number of positive nodes 0 ≤2 positive LN >2 positive LN 164,945 (64.2) 34,652 (90.4) 199,597 (67.6) <0.001 66,833 (26.0) 2,773 (7.2) 69,606 (23.6) 25,017 (9.7) 890 (2.3) 25,907 (8.8) ALND candidacy Negative Positive 231,778 (90.3) 34,652 (90.4) 266,430 (90.3) 0.26 25,017 (9.7) 3,663 (9.6) 28,680 (9.7) Pathologic T stage T0 Tis T1 T2 T3 T4 Unknown 1235 (0.5) 14,012 (36.6) 15,247 (5.2) <0.001 221 (0.1) 1,944 (5.1) 2,166 (0.7) 143,250 (55.8) 12,741 (33.3) 155,991 (52.9) 100,954 (39.3) 5,235 (13.7) 106,189 (36.0) 8,380 (3.3) 572 (1.5) 8,952 (3.0) 628 (0.2) 75 (0.2) 703 (0.2) 221 (0.1) 3,736 (9.8) 5,863 (2.0) Pathologic N Stage 0 i+ N1mi 1 2 3 Unknown 145,283 (61.9) 18,435 (68.2) 163,718 (62.5) <0.001 6,179 (2.6) 314 (1.2) 6,493 (2.5) 12,009 (5.1) 455 (1.7) 12,464 (4.8) 54,326 (23.1) 1,643 (6.1) 55,969 (21.4) 11,097 (4.7) 324 (1.2) 11,421 (4.4) 3,639 (1.6) 79 (0.3) 3,718 (1.4) 2,266 (1.0) 5,779 (21.4) 8,045 (3.1) Lymphovascular Invasion Positive Negative Unknown 4425 (63.9) 19056 (60.4) 23481 (60.9) <0.001 1160 (16.5) 8436 (26.8) 9596 (24.9) 1435 (20.4) 4027 (12.8) 5462 (14.2) Surgical Margins Negative Positive Unknown 245,659 (95.7) 37,153 (97.0) 282,812 (95.8) <0.001 9,676 (3.8) 842 (2.2) 10,518 (3.6) 1460 (0.6) 320 (0.8) 1,780 (0.6) NAC was given to 38,315 patients (13%). Its use increased from 6% in 2010 to 22% in 2021. NAC was administered to 28% of TN, 22% of HER2+, 11% of TP, and only 4% of HR+ patients. Over time, the use of NAC increased across all phenotypes, rising from 11% to 46% in TN, 8% to 34% in HER2+, and 4% to 28% in TP cases. Although NAC administration in HR+ patients increased from 3% in 2010 to 7% in 2021, its overall use remained low. (Figure1) In NAC patients, 37% were ypT0 and 36% were ypT0/ypN0, considered to have pCR. The highest rate of pCR was observed in HER2+ (49%), followed by TN (39%). The pCR rates were 27% and 19% in TP and HR+ patients. The pCR rate increased from 16% in 2010 to 46% in 2021. This increasing pattern was observed in all phenotypes. (Table 2, Figure 2) Table 2: The PCR rate stratified by phenotype over time Year of Diagnosis PCR in TN % PCR in HER2+ % PCR in TP % PCR in HR+ % Total % 2010 22.94 24.18 6.76 6.58 16.24 2011 25.61 36.05 19.44 10.69 21.73 2012 27.19 30.66 14.66 9.58 22.06 2013 29.38 45 19.42 10.49 25.84 2014 32.93 44.9 29.23 12.25 29.95 2015 35.34 51.45 33.94 15.44 34.52 2016 36.89 51.92 29.33 17.5 34.89 2017 36.11 48.41 27.82 20.07 34.73 2018 44.01 52.7 29.14 26.25 41.11 2019 45.99 52.34 29.77 28.59 43.12 2020 45.36 53.66 35.44 29.53 43.06 2021 49.38 56.59 34.82 29.67 45.61 Total 39.15 48.66 27.28 19.06 35.55 Among patients with early-stage breast cancer, 30.3% (72,442 out of 239,280) underwent ALND, though final pathology showed only 26.4% actually required it. In the NAC group, 21.8% (7,622 out of 34,959) underwent ALND, and 24.8% of them had at least one positive lymph node. In contrast, 31.7% (64,820 out of 204,321) of patients treated with upfront surgery (AC group) underwent ALND, with 26.5% having more than two positive lymph nodes, indicating the need for ALND. Overall, ALND was indicated in only 9.8% of AC patients (25,017 out of 256,795) and 9.6% of NAC patients (3,663 out of 38,315), with no statistically significant difference (p = 0.26) (Table 1). When analyzing ALND candidacy (ALNDC) by cancer stage, Stage I patients in the NAC group were more likely to meet criteria for ALND compared to the AC group (10% vs. 8%, p<0.001). Conversely, in Stage II disease, ALNDC was lower in the NAC group than in the AC group (9% vs. 13%, p<0.001) (Table 3). Among TN breast cancer patients, ALNDC was more frequent in the NAC group compared to the AC group (6% vs. 3%, p<0.001), with NAC increasing ALNDC in both Stage I and Stage II TN patients (p<0.001) (Table 3). Similarly, in HR+ patients, ALNDC was higher in the NAC group than in the AC group (24% vs. 13%, p<0.001), with NAC significantly increasing ALNDC in both Stage I and Stage II HR+ patients (p<0.001) (Table 3). ALNDC was also more common in TP patients receiving NAC than AC (11% vs. 7%, p<0.001). Specifically, NAC significantly increased ALNDC in Stage I TP patients (10% vs. 5%, p < 0.001), although no difference was observed between the two groups in Stage II TP patients (11% vs. 12%, p = 0.6) (Table 3). Conversely, in HER2+ patients, ALNDC was lower in the NAC group than in the AC group (5% vs. 6%, p = 0.004). While no difference was observed in Stage I HER2+ patients (5% vs. 5%, p = 0.8), NAC significantly reduced ALNDC in Stage II HER2+ patients (5% vs. 9%, p < 0.001). Table 3: Comparing ALND candidacy between NAC and AC groups stratified by phenotype Stage 1 & 2 cN0 receiving chemotherapy ALND candidacy NAC ACT Total p Stage 1 Positive Negative 1,235 (10.2) 10,870 (89.8) 14,641 (8.3) 162,642(91.7) 15,876 (8.4) 173,512 (91.6) <0.001 Stage 2 Positive Negative 2,428 (9.3) 23,782 (90.7) 10,376 (13.1) 69,136 (87.0) 12,804 (12.1) 92,918 (87.9) <0.001 Stage1&2 Positive Negative 3,663 (9.6) 34,652 (90.4) 25,017 (9.8) 231,778 (90.3) 28,680 (9.7) 266,430 (90.3) 0.26 Total 38,315 (12.98) 256,795 (87.02) 295,110 (100) Triple Negative Stage 1 Positive Negative 414 (5.8) 6,719 (94.2) 859 (2.1) 39,514 (97.9) 1,273 (2.7) 46,233 (97.3) <0.001 Stage 2 Positive Negative 974 (6) 15,407 (94.1) 916 (4.8) 18,125 (95.2) 1,890 (5.3) 33,532 (94.7) <0.001 Stage1&2 Positive Negative 1,388 (5.9) 22,126 (94.1) 1,775 (3.0) 57,639 (97.0) 3,163 (3.8) 79,765 (96.2) <0.001 Total 23,514 (28.4) 59,414 (71.7) 82,928 (100) HR+ Stage 1 Positive Negative 608 (26.4) 1694 (73.6) 12,299 (11.5) 94,967 (88.5) 12,907 (11.8) 96,661 (88.2) <0.001 Stage 2 Positive Negative 1,081 (22.5) 3,730 (77.5) 8,209 (17.0) 40,130 (83.0) 9,290 (17.5) 43,860 (82.5) <0.001 Stage1&2 Positive Negative Total 1,689 (23.8) 5,424 (76.3) 7.113 (4.4) 20,508 (13.2) 135,097 (86.8) 155,605 (95.6) 22,197 (13.6) 140,521 (86.4) 162,718 (100) <0.001 Triple Positive Stage 1 Positive Negative 122 (10.1) 1,082 (89.9) 747 (4.9) 14,524 (95.1) 692 (5.3) 15,606 (94.7) <0.001 Stage 2 Positive Negative 158 (11.9) 1,171 (88.1) 636 (11.4) 4,966 (88.7) 7 (11.5) 6,137 (88.5) 0.58 Stage1&2 Positive Negative 280 (11.1) 2,253 (89.0) 1,383 (6.6) 19,490 (93.4) 1,663 (7.1) 21,743 (92.9) <0.001 Total 2,533 (10.8) 20,873 (89.2) 23,4(100) HER2+ Stage 1 Positive Negative 59 (4.7) 1,185 (95.3) 558 (4.9) 10,854 (95.1) 617 (4.9) 12,039 (95.1) 0.82 Stage 2 Positive Negative 168 (5.1) 3,138 (94.9) 441 (9) 4,461 (91) 609 (7.4) 7,599 (92.6) <0.001 Stage1&2 Positive Negative 227 (5.0) 4,323 (95.0) 999 (6.1) 15,315 (93.9) 1,226 (5.9) 19,638 (94.1) 0.004 Total 4,550 (21.8) 16,314 (78.2) 20,864 (100) ALND: axillary lymph node dissection, NAC: neoadjuvant chemotherapy, AC: adjuvant chemotherapy In the adjusted multivariable regression model, neoadjuvant chemotherapy was associated with an increased rate of ALNDC (OR: 2.5, 95% CI 2.4-2.6; p < 0.001). Other variables associated with a higher likelihood of ALNDC included HR+ phenotype (OR: 2.1, 95 %CI: 2.0-2.2; p<0.001), LVI+ (OR: 4.2, 95% CI: 4.1-4.3; p<0.001), higher CCI, and stage II (OR: 1.2, 95% CI: 1.2-1.3; p<0.001). ALNDC was less likely in HER2+ phenotype (OR: 0.8, 95% CI: 0.7-0.9; p<0.001), TN phenotype (OR: 0.5, 95% CI: 0.5-0.6; p<0.001), and those who underwent breast-conserving surgery (OR: 0.4, 95% CI: 0.4-0.41; p<0.001). There was a decrease in the likelihood of ALNDC over time. (Figure 3, Table 4) Table 4: The association between NAC administration and ALND candidacy Variables OR 95% CI p Charlson Comorbidity Index 0 (Ref) 1 1.1 1.1-1.2 <0.001 2 1.2 1.1-1.4 <0.001 ≥3 1.4 1.2-1.6 <0.001 Chemo sequence <0.001 Adjuvant (Ref) Neoadjuvant 2.5 2.4-2.6 Type of Primary Site Surgery <0.001 Mastectomy (Ref) Breast-Conserving Surgery 0.4 0.4-0.41 Lymphovascular Invasion <0.001 Negative (Ref) Positive 4.2 4.1-4.3 Stage <0.001 Stage I (Ref) Stage II 1.2 1.2-1.3 Phenotype TP (Ref) HR + 2.1 2.0-2.2 <0.001 TN 0.5 0.5-0.6 <0.001 HER2+ 0.8 0.7-0.9 <0.001 Year Of Diagnosis 2010 (Ref) 2011 0.92 0.86-0.98 0.01 2012 0.92 0.87-0.98 0.01 2013 0.86 0.81-0.92 <0.001 2014 0.86 0.81-0.92 <0.001 2015 0.86 0.80-0.91 <0.001 2016 0.83 0.78-0.89 <0.001 2017 0.79 0.74-0.85 <0.001 2018 0.84 0.78-0.90 <0.001 2019 0.74 0.70-0.80 <0.001 2020 0.67 0.63-0.73 <0.001 2021 0.74 0.69-0.79 <0.001 OR: Odds Ratio, CI: Confidence Interval, TP: Triple Positive, HR+: Hormone-Receptor positive, TN: Triple Negative, Discussion In this study, a pathologic complete response (pCR) was achieved in 36% of patients treated with neoadjuvant chemotherapy (NAC). The relatively low pCR rate may be attributed to the study’s time frame, as pCR rates have significantly improved over time, rising from 13% in 2010 to 46% in 2021 across all breast cancer subtypes. Although only 4% of HR + patients received NAC, we observed an increase in the pCR rate from 7–30% over time in this phenotype. This reflects both medicinal advances and advances in tumor profiling, which have contributed to better patient selection [ 22 ]. These successes have led to broader use of neoadjuvant chemotherapy. This study found that NAC use had a fourfold increase between 2010 and 2021 in early-stage breast cancer. The increase in NAC utilization may lead to an unintended consequence of increasing the exposure of certain patient subgroups to the risks associated with ALND. There was no difference in ALNDC between AC and NAC in early-stage breast cancer in this study (p = 0.26). However, adjusted logistic regression models (adjusted for year of diagnosis, stage, and phenotype) revealed an increased ALNDC among the NAC group compared to the AC group (OR: 2.5, 95% CI: 2.4–2.6; p < 0.001). ALNDC was more common in the stage I NAC group compared to the stage I AC group (p < 0.001), but ALNDC was less common in the stage II NAC group compared to the stage II AC group (p < 0.001). These results suggest a potential disadvantage of NAC in Stage I while indicating a possible benefit in Stage II patients regarding axillary management. In stage I breast cancer, ALNDC was higher in NAC compared to AC patients in all phenotypes except HER2 + patients. The high pCR rate and the decreased ALNDC following NAC in HER2 + patients suggest that they are strong candidates for NAC when chemotherapy is indicated. In this study, HR + patients had the lowest pCR rate (19%), and NAC significantly increased ALNDC in both stage I and stage II HR + patients; therefore, NAC may increase the risk of harm through ALND for early-stage HR + patients. Considering the harms of chemotherapy [ 23 ], and based on RxPonder, postmenopausal, node-positive, hormone receptor-positive (HR+) patients may not require chemotherapy (if they have a low genomic score) [ 24 ]. Therefore, NAC administration in this subgroup of patients would be over-treatment with additional harm regarding increased risk of ALND. The primary strength of our study is its use of the NCDB, a large and diverse dataset that is more representative of current and real-world practice. A large population of patients in the NCDB allows for multiple subgroup comparisons and detailed adjusted analyses, which are rarely possible with smaller prospective studies. However, this study has some limitations. The retrospective design of this study is one of the limitations that may lead to selection bias. Furthermore, the systemic treatment regimen is unavailable in the NCDB. It should be noted that the indications for ALND continue to evolve so this question may be a temporary problem. According to the high pCR rate in TNBC, the American Society of Clinical Oncology (ASCO) guidelines recommend neoadjuvant chemotherapy (NAC) for TNBC patients with clinically node-positive disease or tumors at least T1c in size to improve surgical options and assess drug sensitivity. [ 25 ]. These findings have prompted investigators to question whether surgical axillary staging is necessary for patients showing evidence of response. However, accurately determining post-NAC axillary staging to establish when ALND may no longer be required remains challenging. NCCN guideline (NCCN 2025, version 4) encourages SLNB rather than ALND in patients with limited axillary disease. Moreover, in the preliminary results of the A11202 trial, although the final results have not been reported, there is a trend towards omitting ALND in patients with ypN + after NAC [ 24 ]. It is likely that ALND will nearly disappear in the future. But until then, the results in this study indicate that the choice of neoadjuvant chemotherapy may increase the risk of harm through ALND, especially in early-stage HR + patients. Conclusion As long as the standard management of the axilla after NAC in node-negative patients remains surgical, it should be acknowledged that NAC is beneficial in HER2 + early-stage breast cancers and not all early-stage breast cancers with an indication to receive chemotherapy. NAC increases ALNDC in stage I breast cancers and HR + breast cancers. Therefore, despite the undeniable benefits of NAC, too broad an implementation of NAC could have negative effects on some patients. These findings reinforce the importance of selecting the right treatment for the right patient at the right time. Declarations Disclosure: The authors have no disclosures. Author Contribution Mahtab Vasigh performed the analysis and wrote the manuscript.Olutayo Sogunro, Fabian Johnston, David Euhus, and Lisa Jacobs assisted in the study design and final manuscript writing.Fasika Molla Abreha assisted in the analysis.Olutayo Sogunro and David Euhus controlled the results and final manuscript. Data Availability Data is provided in the supplementary information, and the main dataset used for the analysis is stored on Johns Hopkins' Safe Desktop and is available upon request. References Killelea, B.K., et al., Neoadjuvant chemotherapy for breast cancer increases the rate of breast conservation: results from the National Cancer Database. Journal of the American College of Surgeons, 2015. 220 (6): p. 1063-1069. Gianni, L., et al., Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy. Clinical Cancer Research, 2005. 11 (24): p. 8715-8721. Mamtani, A., et al., How often does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? Results of a prospective study. Annals of surgical oncology, 2016. 23 : p. 3467-3474. Derks, M.G. and C.J. van de Velde, Neoadjuvant chemotherapy in breast cancer: more than just downsizing. The Lancet Oncology, 2018. 19 (1): p. 2-3. Kang, Y.-J., et al., Outcome following sentinel lymph node biopsy-guided decisions in breast cancer patients with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy. Breast Cancer Research and Treatment, 2017. 166 : p. 473-480. Fisher, B., et al., Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. Journal of clinical oncology, 1997. 15 (7): p. 2483-2493. Rastogi, P., et al., Preoperative chemotherapy: updates of national surgical adjuvant breast and bowel project protocols B-18 and B-27. Journal of Clinical Oncology, 2008. 26 (5): p. 778-785. Murphy, B.L., et al., Neoadjuvant chemotherapy use in breast cancer is greatest in excellent responders: triple-negative and HER2+ subtypes. Annals of surgical oncology, 2018. 25 : p. 2241-2248. Masuda, N., et al., Adjuvant capecitabine for breast cancer after preoperative chemotherapy. New England Journal of Medicine, 2017. 376 (22): p. 2147-2159. Von Minckwitz, G., et al., Trastuzumab emtansine for residual invasive HER2-positive breast cancer. New England Journal of Medicine, 2019. 380 (7): p. 617-628. Kaufmann, M., et al., Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. Journal of Clinical Oncology, 2006. 24 (12): p. 1940-1949. Teshome, M. and K.K. Hunt, Neoadjuvant therapy in the treatment of breast cancer. Surgical Oncology Clinics, 2014. 23 (3): p. 505-523. Cortazar, P., et al., Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. The Lancet, 2014. 384 (9938): p. 164-172. Network, N.C.C., National Comprehensive Cancer Network Breast Cancer. NCCN Clinical Practice Guidelines in Oncology version. 1 . Kuehn, T., et al., Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. The lancet oncology, 2013. 14 (7): p. 609-618. Pilewskie, M. and M. Morrow, Axillary nodal management following neoadjuvant chemotherapy: a review. JAMA oncology, 2017. 3 (4): p. 549-555. William, J., et al., NCCN guidelines: breast cancer, version 6. J Natl Compr Cancer Netw, 2020. 18 : p. 452-478. Weiss, A., et al., Patterns of axillary management in stages 2 and 3 hormone receptor-positive breast cancer by initial treatment approach. Annals of surgical oncology, 2019. 26 : p. 4326-4336. Gradishar, W.J., et al., Breast cancer, version 3.2020, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network, 2020. 18 (4): p. 452-478. Donker, M., et al., Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. The lancet oncology, 2014. 15 (12): p. 1303-1310. Fleissig, A., Post-operative arm morbidity and quality of life. Results of the ALMANAC randomized trial comparing sentinel node biopsy with standard axillary treatment in the management of patients with early breast cancer. Breast Cancer Res Treat, 2005. 15 : p. 1-15. Boughey, J.C., et al., Nodal pathologic complete response rates in luminal breast cancer vary by genomic risk. Annals of surgical oncology, 2022. 29 (10): p. 6254-6264. Tao, J.J., K. Visvanathan, and A.C. Wolff, Long term side effects of adjuvant chemotherapy in patients with early breast cancer. The Breast, 2015. 24 : p. S149-S153. Jasem, J., et al., The 21-gene recurrence score assay for node-positive, early-stage breast cancer and impact of RxPONDER trial on chemotherapy decision-making: have clinicians already decided? Journal of the National Comprehensive Cancer Network, 2017. 15 (4): p. 494-503. Korde, L.A., et al., Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. Journal of Clinical Oncology, 2021. 39 (13): p. 1485. Schmid, P., et al., Pembrolizumab for early triple-negative breast cancer. New England Journal of Medicine, 2020. 382 (9): p. 810-821. Additional Declarations No competing interests reported. Supplementary Files supplimentarymaterial.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6947236","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":484273655,"identity":"95117549-fd32-422f-897e-703521b1924e","order_by":0,"name":"Mahtab Vasigh","email":"","orcid":"","institution":"Johns Hopkins Medical Institute","correspondingAuthor":false,"prefix":"","firstName":"Mahtab","middleName":"","lastName":"Vasigh","suffix":""},{"id":484273656,"identity":"1d9a9a24-b5f6-4916-b705-f7b417e30f4d","order_by":1,"name":"David Euhus","email":"","orcid":"","institution":"Johns Hopkins Medical Institute","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Euhus","suffix":""},{"id":484273657,"identity":"20cf6e68-2ca7-4f49-8541-55096beb9ddf","order_by":2,"name":"Fabian M Johnston","email":"","orcid":"","institution":"Johns Hopkins Medical Institute","correspondingAuthor":false,"prefix":"","firstName":"Fabian","middleName":"M","lastName":"Johnston","suffix":""},{"id":484273658,"identity":"b20470b5-fe80-4475-a987-ebbcf6d54aa3","order_by":3,"name":"Fasika M Abreha","email":"","orcid":"","institution":"Johns Hopkins Medical Institute","correspondingAuthor":false,"prefix":"","firstName":"Fasika","middleName":"M","lastName":"Abreha","suffix":""},{"id":484273660,"identity":"a31746a8-7be1-440a-9f1e-2ff99e2c1133","order_by":4,"name":"Lisa Jacobs","email":"","orcid":"","institution":"Johns Hopkins Medical Institute","correspondingAuthor":false,"prefix":"","firstName":"Lisa","middleName":"","lastName":"Jacobs","suffix":""},{"id":484273661,"identity":"d48e1f50-3b22-4a3d-b4a2-6a7411722c1e","order_by":5,"name":"Olutayo Sogunro","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYDCCAwyMB1AE+EFEQgFeLUCUgCQg2QDSYkCKFgOwpXi08N0+fOAw7w+7xH7+w4df8+64J2d8fnXihwcGDPL8YgewapE8l5ZwmCchOXHmjLQ0a94zxcZmN95ulgA6zHDm7ASsWgzO8BgAtTAnbrjBY2bM25aQuO3G2Q0gLQkGt/FqqU/ccP4MRMvmGWc3/yBCy+HEDQdyjB+DtGzg792G1xbJM2wJB+ekHTcG+YVxbluCscQN3m0WCQYSOP3Cd4b54IM3NtWyoBD78LYtQY6//+zmmz8qbOT5pbFrgQHHBgYGNgkwUwKsUgKvchCwB2LmD2Am/wGCqkfBKBgFo2BkAQDCn2bxw6ynPQAAAABJRU5ErkJggg==","orcid":"","institution":"Johns Hopkins Medical Institute","correspondingAuthor":true,"prefix":"","firstName":"Olutayo","middleName":"","lastName":"Sogunro","suffix":""}],"badges":[],"createdAt":"2025-06-22 01:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6947236/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6947236/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86672862,"identity":"f445f492-bd91-4f2e-93c5-1b5533909861","added_by":"auto","created_at":"2025-07-14 11:43:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":23214,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003e\u003cstrong\u003eThe trend of neoadjuvant chemotherapy administration over time stratified by phenotype\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNAC: neoadjuvant chemotherapy, TN: triple negative, TP: triple positive, HR: hormone-receptor\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6947236/v1/2f220250287fc47af6d7a8d6.png"},{"id":86672861,"identity":"4e92ec67-6c7a-45ab-b0b6-306b7ca64131","added_by":"auto","created_at":"2025-07-14 11:43:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":26181,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003e\u003cstrong\u003eThe rate of pathologic complete response over time by phenotype\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003ePCR: pathologic complete response, TN: triple negative, TP: triple positive, HR: hormone-receptor\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6947236/v1/81c97fdaab212414ab6c5969.png"},{"id":86672863,"identity":"e3402fb3-e11e-449f-ba3a-afb0596bc591","added_by":"auto","created_at":"2025-07-14 11:43:12","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":96663,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003e\u003cstrong\u003eLogistic regression analysis to evaluate the effect of NAC administration on ALND candidacy, adjusted for CCI, Stage, LVI, phenotype, and year of diagnosis\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAC: adjuvant chemotherapy, NAC: neoadjuvant chemotherapy, CCI: Charlson Comorbidity Index, LVI: Lymphovascular invasion, TP: triple positive, HR: hormone-receptor, TN: triple negative\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6947236/v1/0783414058c3bc1f3ba8523c.png"},{"id":87619303,"identity":"73e967e4-2bce-491d-a391-6d7b05c356e0","added_by":"auto","created_at":"2025-07-26 03:31:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1192551,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6947236/v1/0a90bec2-7fd9-479c-adc8-cff577ba5b63.pdf"},{"id":86673937,"identity":"0189947b-eb7e-4ea6-9a50-7de430ae8e7c","added_by":"auto","created_at":"2025-07-14 11:51:13","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":34947,"visible":true,"origin":"","legend":"","description":"","filename":"supplimentarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-6947236/v1/c248979e67b8193e95176a54.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neoadjuvant Chemotherapy in early-stage breast cancer: the trend over time and the impact on axillary management, A National Cancer Database Analysis","fulltext":[{"header":"Synopsis","content":"\u003cp\u003eThe trend of neoadjuvant chemotherapy utilization in stage I and II breast cancer and its impact on axillary lymph node dissection (ALND) was evaluated. Different indications for ALND in neoadjuvant and adjuvant settings were considered, stratified by phenotype and stage.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eBreast cancer is the second most common cancer among women after skin cancer in the United States. Neoadjuvant chemotherapy (NAC) for breast cancer is a well-established therapeutic approach in certain high-risk patients, including those with large tumors or positive lymph nodes. NAC can decrease tumor size in large tumors, making some patients eligible for breast-conserving surgery or downstaging locally advanced and unresectable primary breast cancers to facilitate resection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. NAC can also eradicate nodal disease in clinically node-positive (cN+) patients, allowing for the avoidance of axillary lymph node dissection (ALND) [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Since the NSABP B-18 and B-27 clinical trials showed similar outcomes in patients receiving NAC versus AC [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], enthusiasm for a neoadjuvant approach in the setting of early-stage breast cancer has intensified, especially in those expected to be excellent responders including the HER2-positive (HER2+) and triple-negative (TN) subtypes [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. NAC can provide an in vivo assessment of tumor response and the invaluable opportunity to deliver targeted therapies in the setting of residual disease [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Pivotal clinical trials, such as KATHERINE and CREATE-X, have shown significantly improved survival rates in HER2\u0026thinsp;+\u0026thinsp;and TNBC patients with residual disease who received adjuvant trastuzumab emtansine (T-DM1) or capecitabine, respectively [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The benefits of NAC are undeniable, but a potential unintended consequence may be increased utilization of axillary dissection. This is because any nodal disease identified after NAC is recommended for ALND. In contrast, patients not receiving NAC can have up to two positive nodes before receiving the same recommendation [\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. ALND is associated with significant risks of neuropathy, lymphedema, and arm dysfunction [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Early-stage small, node-negative breast tumors have an excellent prognosis under current treatment standards. However, rapid advancements in translational data and systemic therapy options make clinical management more complex. In this study, we evaluated the trend of NAC utilization and pathologic complete response (pCR) over time, and compared the rate of ALNDC between NAC and AC patients in early-stage breast cancers.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e After Institutional Review Board (IRB) approval, we performed a retrospective analysis of the National Cancer Database (NCDB). The NCDB is a joint collaboration between the American College of Surgeons and the American Cancer Society. Patient-level data are collected from all cancer patients seen at the Commission on Cancer accredited programs, representing approximately 70% of cancer cases in the United States. From the NCDB breast cancer participant user file (PUF), we identified cN0, cT1-2, M0, stage I, and II female breast cancer patients who had primary site surgery and received chemotherapy between 2010\u0026ndash;2021. Patients with a history of another malignancy, no axillary surgery, unknown clinical or pathologic nodal status, unknown number of positive nodes, those who received pre-operative endocrine therapy or radiotherapy, unknown breast or axillary surgery, and unknown sequence of chemotherapy compared to surgery were excluded. The complete inclusion and exclusion criteria are outlined in the supplemental material. ALND candidacy (ALNDC) was defined separately for the NAC group compared to the AC group. We abstracted the number of removed nodes and the number of positive nodes on the final pathologic assessment, regardless of the axillary management each case has received (sentinel lymph node biopsy or axillary lymph node dissection). ALNDC was considered positive in the NAC group if any positive nodes were documented during the final pathologic nodal evaluation. However, ALNDC was considered positive in the AC group if more than two positive lymph nodes were documented after axillary surgery. Micrometastasis and isolated tumor cells on final pathology were not considered positive. Patients were categorized into four different phenotype groups: 1- hormone receptor-positive (HR+)/HER2\u0026thinsp;+\u0026thinsp;as triple positive (TP); 2- HR+/HER2- as HR+; 3- HR-negative (HR-)/HER2\u0026thinsp;+\u0026thinsp;as HER2+; and 4- HR-/HER2- as triple negative (TN). pCR was defined as ypT0 and ypN0 on the final pathologic report. ypTis was not included in the pCR. We evaluated the Trend of NAC administration and pCR rate between 2010 and 2021. ALNDC was compared between those who received NAC and those who received AC. A subgroup analysis was performed stratified by stage and phenotype. We used descriptive statistics (frequencies, percentages, means, standard deviations) to summarize demographics. Patient and tumor characteristics were compared across subgroups that received NAC and AC, using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. We performed a backward elimination method to select the variables for a multivariable logistic regression model to determine the association between NAC utilization and ALNDC. It was adjusted for the comorbidities (Charlson Comorbidity Index (CCI)), year of diagnosis, stage, lymphovascular invasion (LVI), phenotype, and the type of primary site surgery (mastectomy vs breast-conserving surgery (BCS)). Analysis was performed using Stata software, version 18.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eComparing the neoadjuvant chemotherapy and adjuvant chemotherapy groups:\u003c/p\u003e\n\u003cp\u003eA total of 295,110 eligible patients were identified from the NCDB (Table 1). The mean age of the patients was 57 \u0026plusmn; 12 years; 85% resided in large metropolitan areas, and 64% had private insurance. The patient population consisted of 79% White, 14% African American, and 7% Hispanic individuals. Invasive ductal carcinoma (IDC) constituted 84% of the cases, and 37% of them were grade three. Within this cohort, HER2+ included 7%, TN constituted 28%, and TP and HR+ included 8% and 55%, respectively, and 36% were stage two breast cancers. Of the patients, 42% underwent mastectomy. The mean number of removed nodes was 5.4 \u0026plusmn; 5.9, and the mean number of positive nodes was 0.9 \u0026plusmn; 2.3. The pN0 was observed in 62% of the AC and 69% of the NAC patients. \u0026nbsp;(Table 1) Compared to AC patients, NAC patients were more likely to be clinical stage II (69% versus 31%, p\u0026lt;0.001), cT2 (71% vs. 35%, p\u0026lt;0.001), TN phenotype (61% vs 23%, p\u0026lt;0.001), and more likely to undergo mastectomy (46% vs 41%, p\u0026lt;0.001). The mean number of removed nodes was 4.1 and 5.6 in the NAC and AC groups, respectively. The mean number of positive nodes was 0.2 and 1 in the NAC and AC groups, respectively. (Table 1)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"715\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 715px;\"\u003e\n \u003cp\u003eTable 1: Tumor and patient characteristics based on adjuvant or neoadjuvant chemotherapy administration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003eNAC\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e256,795 (87.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e38,315 (13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e295,110 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 715px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients\u0026apos; Characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eAge at diagnosis (years)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e51.5\u0026plusmn;11.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e55.3\u0026plusmn;11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e56.6\u0026plusmn;12.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eRace \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003cp\u003eBlack\u003c/p\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e205,413 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e28,577 (74.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e233,990 (79.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e34,377 (13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e6,902 (18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e41,279 (14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e8,964 (3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e1,361 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e10,325 (3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e8,041 (3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e1,475 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e9,516 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eCharlson Comorbidity Index\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e\u0026ge;3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e216,836 (84.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e33,245 (86.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e250,090 (84.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e31,565 (12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e3,884 (10.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e35,449 (12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e5,949 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e794 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e6,743 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e2,445 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e383 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e2,828 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 715px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor Characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e\n \u003cp\u003eInvasive lobular carcinoma\u003c/p\u003e\n \u003cp\u003eMixed invasive ductal and lobular\u003c/p\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e211,558 (82.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e35,128 (91.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e246,686 (83.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"12\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e18,147 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e652 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e18,799 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e16,314 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e906 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e17,220 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e10,773 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e1,625 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e12,398 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eTumor Grade\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e16,606 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e642 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e17,248 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e70,657 (27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e4,775 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e75,432 (25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e95,224 (37.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e14,887 (38.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e110,111 (37.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e74,308 (28.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e18,011 (47.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e92,319 (31.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eEstrogen Receptor\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Negative\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e81,117 (31.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e29,569 (77.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e110,686 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e174,936 (68.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e8,611 (22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e183,547 (62.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e742 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e135 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e877 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eProgesterone Receptor\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Negative\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e108,533 (42.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e31,141 (81.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e139,647 (74.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"11\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e147,296 (57.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e7,016 (18.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e154,312 (52.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e966 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e158 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e1,124 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eTumor Phenotype\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Triple Positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Hormone Positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;HER2 positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Triple Negative\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e20,873 (8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e2,533 (6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e23,406 (7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e155,605 (60.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e7,113 (18.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e162,718 (55.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e16,314 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e4,550 (11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e20,864 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"5\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e59,414 (23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e23,514 (61.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e82,928 (28.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e4,589 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e605 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e5,194 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eclinical T Stage\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;cT1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;cT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e168,131 (65.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e11123 (29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e179,254 (60.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"5\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e88,664 (34.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e27,192 (71.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e115,856 (39.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eClinical Stage Group\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e177,283 (69.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e12105 (31.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e189,388 (64.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"4\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e79,512 (31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e26,210 (68.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e105,722 (35.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 715px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eType of Surgery\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Mastectomy\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Breast-Conserving Surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 517px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"30\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 517px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"15\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e104,796 (40.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e17,689 (46.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e122,480 (41.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e151,999 (59.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e20,631 (53.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e172,630 (58.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"10\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eType of Axillary Surgery\u003c/p\u003e\n \u003cp\u003eALND\u003c/p\u003e\n \u003cp\u003eSLNB\u003c/p\u003e\n \u003cp\u003eSNLB+ALND\u003c/p\u003e\n \u003cp\u003eNo Surgery\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e59,249 (29)\u003c/p\u003e\n \u003cp\u003e138,758 (67.9)\u003c/p\u003e\n \u003cp\u003e5,571 (2.7)\u003c/p\u003e\n \u003cp\u003e492 (0.2)\u003c/p\u003e\n \u003cp\u003e251 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7,145 (20.4)\u003c/p\u003e\n \u003cp\u003e27,163 (77.7)\u003c/p\u003e\n \u003cp\u003e477 (1.4)\u003c/p\u003e\n \u003cp\u003e121 (0.4)\u003c/p\u003e\n \u003cp\u003e53 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e66,394 (27.8)\u003c/p\u003e\n \u003cp\u003e165,921 (69.3)\u003c/p\u003e\n \u003cp\u003e6,048 (2.5)\u003c/p\u003e\n \u003cp\u003e613 (0.3)\u003c/p\u003e\n \u003cp\u003e304 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eTreatment (Endocrine Therapy)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Negative\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e92,168 (35.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e32,453 (84.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e124,621 (42.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e160,441 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e5,122 (13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e165,563 (56.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e4,186 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e740 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e4926 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"6\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eAnti HER2 Therapy (2013+)\u003c/p\u003e\n \u003cp\u003eHER2+ \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Negative\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eTP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Negative \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;3,588 (93.7)\u003c/p\u003e\n \u003cp\u003e235 (6.1)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1958 (62.4)\u003c/p\u003e\n \u003cp\u003e1154 (36.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1530 (88.4)\u003c/p\u003e\n \u003cp\u003e197 (11.4)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e711 (73.4)\u003c/p\u003e\n \u003cp\u003e252 (26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5,118 (92.1)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;432 (7.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2,669 (65.0)\u003c/p\u003e\n \u003cp\u003e1,406 (34.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"88\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 715px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathologic Outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eNumber of regional lymph nodes examined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e5.54\u0026plusmn;6.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e4.07\u0026plusmn;4.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e5.35\u0026plusmn;5.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"9\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003enumber of regional lymph nodes positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e0.95\u0026plusmn;2.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e0.22\u0026plusmn;1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e0.85\u0026plusmn;2.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"4\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003enumber of positive nodes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026le;2 positive LN\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026gt;2 positive LN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e164,945 (64.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e34,652 (90.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e199,597 (67.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e66,833 (26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e2,773 (7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e69,606 (23.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"7\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e25,017 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e890 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e25,907 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eALND candidacy\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNegative\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e231,778 (90.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e34,652 (90.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e266,430 (90.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e25,017 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e3,663 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e28,680 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"8\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ePathologic T stage\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;T0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Tis\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;T1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;T2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;T3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;T4\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1235 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e14,012 (36.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e15,247 (5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e221 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e1,944 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e2,166 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e143,250 (55.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e12,741 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e155,991 (52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"4\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e100,954 (39.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e5,235 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e106,189 (36.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"7\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e8,380 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e572 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e8,952 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"4\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e628 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e75 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e703 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"7\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e221 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e3,736 (9.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e5,863 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"8\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ePathologic N Stage\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;i+\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;N1mi\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e145,283 (61.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e18,435 (68.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e163,718 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e6,179 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e314 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e6,493 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"7\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e12,009 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e455 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e12,464 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e54,326 (23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e1,643 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e55,969 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e11,097 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e324 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e11,421 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e3,639 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e79 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e3,718 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e2,266 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e5,779 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e8,045 (3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eLymphovascular Invasion\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Negative\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e4425 (63.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e19056 (60.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e23481 (60.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1160 (16.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e8436 (26.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e9596 (24.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1435 (20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e4027 (12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e5462 (14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eSurgical Margins\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Negative\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e245,659 (95.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e37,153 (97.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e282,812 (95.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e9,676 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e842 (2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e10,518 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1460 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e320 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e1,780 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd height=\"3\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNAC was given to 38,315 patients (13%). Its use increased from 6% in 2010 to 22% in 2021. NAC was administered to 28% of TN, 22% of HER2+, 11% of TP, and only 4% of HR+ patients. Over time, the use of NAC increased across all phenotypes, rising from 11% to 46% in TN, 8% to 34% in HER2+, and 4% to 28% in TP cases. Although NAC administration in HR+ patients increased from 3% in 2010 to 7% in 2021, its overall use remained low. (Figure1)\u003c/p\u003e\n\u003cp\u003eIn NAC patients, 37% were ypT0 and 36% were ypT0/ypN0, considered to have pCR. The highest rate of pCR was observed in HER2+ (49%), followed by TN (39%). The pCR rates were 27% and 19% in TP and HR+ patients. The pCR rate increased from 16% in 2010 to 46% in 2021. This increasing pattern was observed in all phenotypes. (Table 2, Figure 2)\u003c/p\u003e\n\u003cp\u003eTable 2: The PCR rate stratified by phenotype over time\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003eYear of Diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003ePCR in TN %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003ePCR in HER2+ %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003ePCR in TP %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003ePCR in HR+ %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eTotal %\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e22.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e24.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e6.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e6.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e16.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e25.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e36.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e19.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e10.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e21.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e27.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e30.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e14.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e9.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e22.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e29.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e19.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e10.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e25.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e32.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e44.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e29.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e12.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e29.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e35.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e51.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e33.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e15.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e34.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e36.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e51.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e29.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e34.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e36.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e48.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e27.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e20.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e34.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e44.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e52.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e29.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e26.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e41.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e45.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e52.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e29.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e28.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e43.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e45.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e53.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e35.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e29.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e43.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e49.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e56.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e34.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e29.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e45.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e39.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e48.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e27.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e19.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e35.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAmong patients with early-stage breast cancer, 30.3% (72,442 out of 239,280) underwent ALND, though final pathology showed only 26.4% actually required it. In the NAC group, 21.8% (7,622 out of 34,959) underwent ALND, and 24.8% of them had at least one positive lymph node. In contrast, 31.7% (64,820 out of 204,321) of patients treated with upfront surgery (AC group) underwent ALND, with 26.5% having more than two positive lymph nodes, indicating the need for ALND. Overall, ALND was indicated in only 9.8% of AC patients (25,017 out of 256,795) and 9.6% of NAC patients (3,663 out of 38,315), with no statistically significant difference (p = 0.26) (Table 1).\u003c/p\u003e\n\u003cp\u003eWhen analyzing ALND candidacy (ALNDC) by cancer stage, Stage I patients in the NAC group were more likely to meet criteria for ALND compared to the AC group (10% vs. 8%, p\u0026lt;0.001). Conversely, in Stage II disease, ALNDC was lower in the NAC group than in the AC group (9% vs. 13%, p\u0026lt;0.001) (Table 3).\u003c/p\u003e\n\u003cp\u003eAmong TN breast cancer patients, ALNDC was more frequent in the NAC group compared to the AC group (6% vs. 3%, p\u0026lt;0.001), with NAC increasing ALNDC in both Stage I and Stage II TN patients (p\u0026lt;0.001) (Table 3). Similarly, in HR+ patients, ALNDC was higher in the NAC group than in the AC group (24% vs. 13%, p\u0026lt;0.001), with NAC significantly increasing ALNDC in both Stage I and Stage II HR+ patients (p\u0026lt;0.001) (Table 3). ALNDC was also more common in TP patients receiving NAC than AC (11% vs. 7%, p\u0026lt;0.001). Specifically, NAC significantly increased ALNDC in Stage I TP patients (10% vs. 5%, p \u0026lt; 0.001), although no difference was observed between the two groups in Stage II TP patients (11% vs. 12%, p = 0.6) (Table 3). Conversely, in HER2+ patients, ALNDC was lower in the NAC group than in the AC group (5% vs. 6%, p = 0.004). While no difference was observed in Stage I HER2+ patients (5% vs. 5%, p = 0.8), NAC significantly reduced ALNDC in Stage II HER2+ patients (5% vs. 9%, p \u0026lt; 0.001).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 584px;\"\u003e\n \u003cp\u003eTable 3: Comparing ALND candidacy between NAC and AC groups stratified by phenotype\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 584px;\"\u003e\n \u003cp\u003eStage 1 \u0026amp; 2 cN0 receiving chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eALND candidacy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003eNAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eACT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage 1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,235 (10.2)\u003c/p\u003e\n \u003cp\u003e10,870 (89.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14,641 (8.3)\u003c/p\u003e\n \u003cp\u003e162,642(91.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15,876 (8.4)\u003c/p\u003e\n \u003cp\u003e173,512 (91.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2,428 (9.3)\u003c/p\u003e\n \u003cp\u003e23,782 (90.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10,376 (13.1)\u003c/p\u003e\n \u003cp\u003e69,136 (87.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12,804 (12.1)\u003c/p\u003e\n \u003cp\u003e92,918 (87.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage1\u0026amp;2\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3,663 (9.6)\u003c/p\u003e\n \u003cp\u003e34,652 (90.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25,017 (9.8)\u003c/p\u003e\n \u003cp\u003e231,778 (90.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28,680 (9.7)\u003c/p\u003e\n \u003cp\u003e266,430 (90.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e38,315 (12.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e256,795 (87.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e295,110 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 584px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTriple Negative\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage 1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e414 (5.8)\u003c/p\u003e\n \u003cp\u003e6,719 (94.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e859 (2.1)\u003c/p\u003e\n \u003cp\u003e39,514 (97.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,273 (2.7)\u003c/p\u003e\n \u003cp\u003e46,233 (97.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e974 (6)\u003c/p\u003e\n \u003cp\u003e15,407 (94.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e916 (4.8)\u003c/p\u003e\n \u003cp\u003e18,125 (95.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,890 (5.3)\u003c/p\u003e\n \u003cp\u003e33,532 (94.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage1\u0026amp;2\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,388 (5.9)\u003c/p\u003e\n \u003cp\u003e22,126 (94.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,775 (3.0)\u003c/p\u003e\n \u003cp\u003e57,639 (97.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3,163 (3.8)\u003c/p\u003e\n \u003cp\u003e79,765 (96.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e23,514 (28.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e59,414 (71.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e82,928 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 584px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR+\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage 1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e608 (26.4)\u003c/p\u003e\n \u003cp\u003e1694 (73.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12,299 (11.5)\u003c/p\u003e\n \u003cp\u003e94,967 (88.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12,907 (11.8)\u003c/p\u003e\n \u003cp\u003e96,661 (88.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,081 (22.5)\u003c/p\u003e\n \u003cp\u003e3,730 (77.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8,209 (17.0)\u003c/p\u003e\n \u003cp\u003e40,130 (83.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9,290 (17.5)\u003c/p\u003e\n \u003cp\u003e43,860 (82.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage1\u0026amp;2\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,689 (23.8)\u003c/p\u003e\n \u003cp\u003e5,424 (76.3)\u003c/p\u003e\n \u003cp\u003e7.113 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20,508 (13.2)\u003c/p\u003e\n \u003cp\u003e135,097 (86.8)\u003c/p\u003e\n \u003cp\u003e155,605 (95.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22,197 (13.6)\u003c/p\u003e\n \u003cp\u003e140,521 (86.4)\u003c/p\u003e\n \u003cp\u003e162,718 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 584px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTriple Positive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage 1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e122 (10.1)\u003c/p\u003e\n \u003cp\u003e1,082 (89.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e747 (4.9)\u003c/p\u003e\n \u003cp\u003e14,524 (95.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e692 (5.3)\u003c/p\u003e\n \u003cp\u003e15,606 (94.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e158 (11.9)\u003c/p\u003e\n \u003cp\u003e1,171 (88.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e636 (11.4)\u003c/p\u003e\n \u003cp\u003e4,966 (88.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (11.5)\u003c/p\u003e\n \u003cp\u003e6,137 (88.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage1\u0026amp;2\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e280 (11.1)\u003c/p\u003e\n \u003cp\u003e2,253 (89.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,383 (6.6)\u003c/p\u003e\n \u003cp\u003e19,490 (93.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,663 (7.1)\u003c/p\u003e\n \u003cp\u003e21,743 (92.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e2,533 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e20,873 (89.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e23,4(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 584px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHER2+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage 1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e59 (4.7)\u003c/p\u003e\n \u003cp\u003e1,185 (95.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e558 (4.9)\u003c/p\u003e\n \u003cp\u003e10,854 (95.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e617 (4.9)\u003c/p\u003e\n \u003cp\u003e12,039 (95.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e168 (5.1)\u003c/p\u003e\n \u003cp\u003e3,138 (94.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e441 (9)\u003c/p\u003e\n \u003cp\u003e4,461 (91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e609 (7.4)\u003c/p\u003e\n \u003cp\u003e7,599 (92.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eStage1\u0026amp;2\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e227 (5.0)\u003c/p\u003e\n \u003cp\u003e4,323 (95.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e999 (6.1)\u003c/p\u003e\n \u003cp\u003e15,315 (93.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,226 (5.9)\u003c/p\u003e\n \u003cp\u003e19,638 (94.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.5736%;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.066%;\"\u003e\n \u003cp\u003e4,550 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e16,314 (78.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e20,864 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 584px;\"\u003e\n \u003cp\u003eALND: axillary lymph node dissection, NAC: neoadjuvant chemotherapy, AC: adjuvant chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIn the adjusted multivariable regression model, neoadjuvant chemotherapy was associated with an increased rate of ALNDC (OR: 2.5, 95% CI 2.4-2.6; p \u0026lt; 0.001). Other variables associated with a higher likelihood of ALNDC included HR+ phenotype (OR: 2.1, 95 %CI: 2.0-2.2; p\u0026lt;0.001), LVI+ (OR: 4.2, 95% CI: 4.1-4.3; p\u0026lt;0.001), higher CCI, and stage II (OR: 1.2, 95% CI: 1.2-1.3; p\u0026lt;0.001). ALNDC was less likely in HER2+ phenotype (OR: 0.8, 95% CI: 0.7-0.9; p\u0026lt;0.001), TN phenotype (OR: 0.5, 95% CI: 0.5-0.6; p\u0026lt;0.001), and those who underwent breast-conserving surgery (OR: 0.4, 95% CI: 0.4-0.41; p\u0026lt;0.001). There was a decrease in the likelihood of ALNDC over time. (Figure 3, Table 4)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"480\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 480px;\"\u003e\n \u003cp\u003eTable 4: The association between NAC administration and ALND candidacy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 252px;\"\u003e\n \u003cp\u003eCharlson Comorbidity Index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e0 (Ref)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e1.1-1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e1.1-1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u0026ge;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e1.2-1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 252px;\"\u003e\n \u003cp\u003eChemo sequence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003eAdjuvant (Ref)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003eNeoadjuvant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e2.4-2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 252px;\"\u003e\n \u003cp\u003eType of Primary Site Surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003eMastectomy (Ref)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003eBreast-Conserving Surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.4-0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 252px;\"\u003e\n \u003cp\u003eLymphovascular Invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003eNegative (Ref)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e4.1-4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003eStage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003eStage I (Ref)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003eStage II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e1.2-1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePhenotype\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003eTP (Ref)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003eHR +\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 2.0-2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003eTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.5-0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003eHER2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.7-0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 252px;\"\u003e\n \u003cp\u003eYear Of Diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003e2010 (Ref)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.86-0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003e2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.87-0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.81-0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.81-0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.80-0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.78-0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.74-0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.78-0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.70-0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 165px;\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.63-0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.69-0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 480px;\"\u003e\n \u003cp\u003eOR: Odds Ratio, CI: Confidence Interval, TP: Triple Positive, HR+: Hormone-Receptor positive, TN: Triple Negative,\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, a pathologic complete response (pCR) was achieved in 36% of patients treated with neoadjuvant chemotherapy (NAC). The relatively low pCR rate may be attributed to the study\u0026rsquo;s time frame, as pCR rates have significantly improved over time, rising from 13% in 2010 to 46% in 2021 across all breast cancer subtypes. Although only 4% of HR\u0026thinsp;+\u0026thinsp;patients received NAC, we observed an increase in the pCR rate from 7\u0026ndash;30% over time in this phenotype. This reflects both medicinal advances and advances in tumor profiling, which have contributed to better patient selection [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. These successes have led to broader use of neoadjuvant chemotherapy. This study found that NAC use had a fourfold increase between 2010 and 2021 in early-stage breast cancer. The increase in NAC utilization may lead to an unintended consequence of increasing the exposure of certain patient subgroups to the risks associated with ALND. There was no difference in ALNDC between AC and NAC in early-stage breast cancer in this study (p\u0026thinsp;=\u0026thinsp;0.26). However, adjusted logistic regression models (adjusted for year of diagnosis, stage, and phenotype) revealed an increased ALNDC among the NAC group compared to the AC group (OR: 2.5, 95% CI: 2.4\u0026ndash;2.6; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). ALNDC was more common in the stage I NAC group compared to the stage I AC group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), but ALNDC was less common in the stage II NAC group compared to the stage II AC group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These results suggest a potential disadvantage of NAC in Stage I while indicating a possible benefit in Stage II patients regarding axillary management. In stage I breast cancer, ALNDC was higher in NAC compared to AC patients in all phenotypes except HER2\u0026thinsp;+\u0026thinsp;patients. The high pCR rate and the decreased ALNDC following NAC in HER2\u0026thinsp;+\u0026thinsp;patients suggest that they are strong candidates for NAC when chemotherapy is indicated. In this study, HR\u0026thinsp;+\u0026thinsp;patients had the lowest pCR rate (19%), and NAC significantly increased ALNDC in both stage I and stage II HR\u0026thinsp;+\u0026thinsp;patients; therefore, NAC may increase the risk of harm through ALND for early-stage HR\u0026thinsp;+\u0026thinsp;patients. Considering the harms of chemotherapy [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], and based on RxPonder, postmenopausal, node-positive, hormone receptor-positive (HR+) patients may not require chemotherapy (if they have a low genomic score) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Therefore, NAC administration in this subgroup of patients would be over-treatment with additional harm regarding increased risk of ALND.\u003c/p\u003e\u003cp\u003eThe primary strength of our study is its use of the NCDB, a large and diverse dataset that is more representative of current and real-world practice. A large population of patients in the NCDB allows for multiple subgroup comparisons and detailed adjusted analyses, which are rarely possible with smaller prospective studies. However, this study has some limitations. The retrospective design of this study is one of the limitations that may lead to selection bias. Furthermore, the systemic treatment regimen is unavailable in the NCDB. It should be noted that the indications for ALND continue to evolve so this question may be a temporary problem.\u003c/p\u003e\u003cp\u003e According to the high pCR rate in TNBC, the American Society of Clinical Oncology (ASCO) guidelines recommend neoadjuvant chemotherapy (NAC) for TNBC patients with clinically node-positive disease or tumors at least T1c in size to improve surgical options and assess drug sensitivity. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. These findings have prompted investigators to question whether surgical axillary staging is necessary for patients showing evidence of response. However, accurately determining post-NAC axillary staging to establish when ALND may no longer be required remains challenging. NCCN guideline (NCCN 2025, version 4) encourages SLNB rather than ALND in patients with limited axillary disease. Moreover, in the preliminary results of the A11202 trial, although the final results have not been reported, there is a trend towards omitting ALND in patients with ypN\u0026thinsp;+\u0026thinsp;after NAC [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. It is likely that ALND will nearly disappear in the future. But until then, the results in this study indicate that the choice of neoadjuvant chemotherapy may increase the risk of harm through ALND, especially in early-stage HR\u0026thinsp;+\u0026thinsp;patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAs long as the standard management of the axilla after NAC in node-negative patients remains surgical, it should be acknowledged that NAC is beneficial in HER2\u0026thinsp;+\u0026thinsp;early-stage breast cancers and not all early-stage breast cancers with an indication to receive chemotherapy. NAC increases ALNDC in stage I breast cancers and HR\u0026thinsp;+\u0026thinsp;breast cancers. Therefore, despite the undeniable benefits of NAC, too broad an implementation of NAC could have negative effects on some patients. These findings reinforce the importance of selecting the right treatment for the right patient at the right time.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eDisclosure:\u003c/h2\u003e\u003cp\u003eThe authors have no disclosures.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eMahtab Vasigh performed the analysis and wrote the manuscript.Olutayo Sogunro, Fabian Johnston, David Euhus, and Lisa Jacobs assisted in the study design and final manuscript writing.Fasika Molla Abreha assisted in the analysis.Olutayo Sogunro and David Euhus controlled the results and final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is provided in the supplementary information, and the main dataset used for the analysis is stored on Johns Hopkins' Safe Desktop and is available upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eKillelea, B.K., et al., \u003cem\u003eNeoadjuvant chemotherapy for breast cancer increases the rate of breast conservation: results from the National Cancer Database.\u003c/em\u003e Journal of the American College of Surgeons, 2015. \u003cstrong\u003e220\u003c/strong\u003e(6): p. 1063-1069.\u003c/li\u003e\n \u003cli\u003eGianni, L., et al., \u003cem\u003eFeasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy.\u003c/em\u003e Clinical Cancer Research, 2005. \u003cstrong\u003e11\u003c/strong\u003e(24): p. 8715-8721.\u003c/li\u003e\n \u003cli\u003eMamtani, A., et al., \u003cem\u003eHow often does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? Results of a prospective study.\u003c/em\u003e Annals of surgical oncology, 2016. \u003cstrong\u003e23\u003c/strong\u003e: p. 3467-3474.\u003c/li\u003e\n \u003cli\u003eDerks, M.G. and C.J. van de Velde, \u003cem\u003eNeoadjuvant chemotherapy in breast cancer: more than just downsizing.\u003c/em\u003e The Lancet Oncology, 2018. \u003cstrong\u003e19\u003c/strong\u003e(1): p. 2-3.\u003c/li\u003e\n \u003cli\u003eKang, Y.-J., et al., \u003cem\u003eOutcome following sentinel lymph node biopsy-guided decisions in breast cancer patients with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy.\u003c/em\u003e Breast Cancer Research and Treatment, 2017. \u003cstrong\u003e166\u003c/strong\u003e: p. 473-480.\u003c/li\u003e\n \u003cli\u003eFisher, B., et al., \u003cem\u003eEffect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18.\u003c/em\u003e Journal of clinical oncology, 1997. \u003cstrong\u003e15\u003c/strong\u003e(7): p. 2483-2493.\u003c/li\u003e\n \u003cli\u003eRastogi, P., et al., \u003cem\u003ePreoperative chemotherapy: updates of national surgical adjuvant breast and bowel project protocols B-18 and B-27.\u003c/em\u003e Journal of Clinical Oncology, 2008. \u003cstrong\u003e26\u003c/strong\u003e(5): p. 778-785.\u003c/li\u003e\n \u003cli\u003eMurphy, B.L., et al., \u003cem\u003eNeoadjuvant chemotherapy use in breast cancer is greatest in excellent responders: triple-negative and HER2+ subtypes.\u003c/em\u003e Annals of surgical oncology, 2018. \u003cstrong\u003e25\u003c/strong\u003e: p. 2241-2248.\u003c/li\u003e\n \u003cli\u003eMasuda, N., et al., \u003cem\u003eAdjuvant capecitabine for breast cancer after preoperative chemotherapy.\u003c/em\u003e New England Journal of Medicine, 2017. \u003cstrong\u003e376\u003c/strong\u003e(22): p. 2147-2159.\u003c/li\u003e\n \u003cli\u003eVon Minckwitz, G., et al., \u003cem\u003eTrastuzumab emtansine for residual invasive HER2-positive breast cancer.\u003c/em\u003e New England Journal of Medicine, 2019. \u003cstrong\u003e380\u003c/strong\u003e(7): p. 617-628.\u003c/li\u003e\n \u003cli\u003eKaufmann, M., et al., \u003cem\u003eRecommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update.\u003c/em\u003e Journal of Clinical Oncology, 2006. \u003cstrong\u003e24\u003c/strong\u003e(12): p. 1940-1949.\u003c/li\u003e\n \u003cli\u003eTeshome, M. and K.K. Hunt, \u003cem\u003eNeoadjuvant therapy in the treatment of breast cancer.\u003c/em\u003e Surgical Oncology Clinics, 2014. \u003cstrong\u003e23\u003c/strong\u003e(3): p. 505-523.\u003c/li\u003e\n \u003cli\u003eCortazar, P., et al., \u003cem\u003ePathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.\u003c/em\u003e The Lancet, 2014. \u003cstrong\u003e384\u003c/strong\u003e(9938): p. 164-172.\u003c/li\u003e\n \u003cli\u003eNetwork, N.C.C., \u003cem\u003eNational Comprehensive Cancer Network Breast Cancer.\u003c/em\u003e NCCN Clinical Practice Guidelines in Oncology version. \u003cstrong\u003e1\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003eKuehn, T., et al., \u003cem\u003eSentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study.\u003c/em\u003e The lancet oncology, 2013. \u003cstrong\u003e14\u003c/strong\u003e(7): p. 609-618.\u003c/li\u003e\n \u003cli\u003ePilewskie, M. and M. Morrow, \u003cem\u003eAxillary nodal management following neoadjuvant chemotherapy: a review.\u003c/em\u003e JAMA oncology, 2017. \u003cstrong\u003e3\u003c/strong\u003e(4): p. 549-555.\u003c/li\u003e\n \u003cli\u003eWilliam, J., et al., \u003cem\u003eNCCN guidelines: breast cancer, version 6.\u003c/em\u003e J Natl Compr Cancer Netw, 2020. \u003cstrong\u003e18\u003c/strong\u003e: p. 452-478.\u003c/li\u003e\n \u003cli\u003eWeiss, A., et al., \u003cem\u003ePatterns of axillary management in stages 2 and 3 hormone receptor-positive breast cancer by initial treatment approach.\u003c/em\u003e Annals of surgical oncology, 2019. \u003cstrong\u003e26\u003c/strong\u003e: p. 4326-4336.\u003c/li\u003e\n \u003cli\u003eGradishar, W.J., et al., \u003cem\u003eBreast cancer, version 3.2020, NCCN clinical practice guidelines in oncology.\u003c/em\u003e Journal of the National Comprehensive Cancer Network, 2020. \u003cstrong\u003e18\u003c/strong\u003e(4): p. 452-478.\u003c/li\u003e\n \u003cli\u003eDonker, M., et al., \u003cem\u003eRadiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial.\u003c/em\u003e The lancet oncology, 2014. \u003cstrong\u003e15\u003c/strong\u003e(12): p. 1303-1310.\u003c/li\u003e\n \u003cli\u003eFleissig, A., \u003cem\u003ePost-operative arm morbidity and quality of life. Results of the ALMANAC randomized trial comparing sentinel node biopsy with standard axillary treatment in the management of patients with early breast cancer.\u003c/em\u003e Breast Cancer Res Treat, 2005. \u003cstrong\u003e15\u003c/strong\u003e: p. 1-15.\u003c/li\u003e\n \u003cli\u003eBoughey, J.C., et al., \u003cem\u003eNodal pathologic complete response rates in luminal breast cancer vary by genomic risk.\u003c/em\u003e Annals of surgical oncology, 2022. \u003cstrong\u003e29\u003c/strong\u003e(10): p. 6254-6264.\u003c/li\u003e\n \u003cli\u003eTao, J.J., K. Visvanathan, and A.C. Wolff, \u003cem\u003eLong term side effects of adjuvant chemotherapy in patients with early breast cancer.\u003c/em\u003e The Breast, 2015. \u003cstrong\u003e24\u003c/strong\u003e: p. S149-S153.\u003c/li\u003e\n \u003cli\u003eJasem, J., et al., \u003cem\u003eThe 21-gene recurrence score assay for node-positive, early-stage breast cancer and impact of RxPONDER trial on chemotherapy decision-making: have clinicians already decided?\u003c/em\u003e Journal of the National Comprehensive Cancer Network, 2017. \u003cstrong\u003e15\u003c/strong\u003e(4): p. 494-503.\u003c/li\u003e\n \u003cli\u003eKorde, L.A., et al., \u003cem\u003eNeoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline.\u003c/em\u003e Journal of Clinical Oncology, 2021. \u003cstrong\u003e39\u003c/strong\u003e(13): p. 1485.\u003c/li\u003e\n \u003cli\u003eSchmid, P., et al., \u003cem\u003ePembrolizumab for early triple-negative breast cancer.\u003c/em\u003e New England Journal of Medicine, 2020. \u003cstrong\u003e382\u003c/strong\u003e(9): p. 810-821.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Neoadjuvant chemotherapy, Axillary lymph node dissection, Early-stage breast cancer, Stage I \u0026 stage II breast cancer, pathologic complete response (pCR), Trend of neoadjuvant chemotherapy over time","lastPublishedDoi":"10.21203/rs.3.rs-6947236/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6947236/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Despite several benefits to neoadjuvant chemotherapy (NAC), there are uncertainties about NAC utilization in early breast cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We performed a retrospective analysis of the National Cancer Database (NCDB), selecting cN0, cT1-2, M0 breast cancers who received chemotherapy between 2010 and 2021. Axillary lymph node dissection candidacy (ALNDC) was considered positive in the NAC group if any positive nodes were recorded, and in the AC group if more than two positive nodes were documented after surgery. The trend of NAC use and pathologic complete response (pCR) rate over time was assessed. ALNDC was compared between NAC and adjuvant chemotherapy (AC), stratified by stage and phenotype.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e In a cohort of 295,110 patients, NAC was administered in 13%, increasing from 6% in 2010 to 22% in 2021. While 36% achieved pCR, increasing from 16% in 2010 to 46% in 2021. ALNDC was observed in 9.6% of the NAC and 9.7% of the AC groups (p = 0.2). NAC increased ALNDC in stage I patients (10% vs 8%, p\u0026lt;0.001). However, NAC decreased ALNDC in stage II patients (9% vs. 13%, p \u0026lt; 0.001). NAC increased the rate of ALNDC in hormone-receptor-positive (HR+) (24% vs 13%, p\u0026lt;0.001). However, it decreased ALNDC in HER2+ patients (5% vs 6%, p = 0.004). In the adjusted multivariable analysis, NAC increased the ALNDC (OR: 2.5, 95% CI 2.4-2.6; p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eDespite the undeniable benefits of NAC, our results revealed an increase in ALNDC in HR+ and stage I breast cancer patients and a decrease in ALNDC in HER2+ patients compared to the AC group. This reinforces the importance of selecting the right treatment for the right patient at the right time.\u003c/p\u003e","manuscriptTitle":"Neoadjuvant Chemotherapy in early-stage breast cancer: the trend over time and the impact on axillary management, A National Cancer Database Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-14 11:43:08","doi":"10.21203/rs.3.rs-6947236/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b5e7d810-6b3d-4c42-8c02-a7e9cd2abe16","owner":[],"postedDate":"July 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-26T03:23:31+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-14 11:43:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6947236","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6947236","identity":"rs-6947236","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}