10-Year Outcomes of Targeted Axillary Surgery after Neoadjuvant Chemotherapy in Breast Cancer

10-Year Outcomes of Targeted Axillary Surgery after Neoadjuvant Chemotherapy in Breast Cancer | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article 10-Year Outcomes of Targeted Axillary Surgery after Neoadjuvant Chemotherapy in Breast Cancer Jeeyeon Lee, Byeongju Kang, Hye Jung Kim, Won Hwa Kim, Yee Soo Chae, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5004479/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: When pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is achieved, identifying traces of the previous tumor site or lymph nodes and performing accurate surgery becomes challenging. We conducted ultrasound-guided targeted axillary surgery (TAS) in patients with node-positive breast cancer treated with NAC. Survival outcomes were compared with those of patients who underwent conventional axillary lymph node dissection (ALND). Methods: We conducted a retrospective analysis of 235 patients (TAS, n=78; ALND, n=157) with cT1-3N1-2 breast cancer who underwent NAC followed by surgery from 2012 to 2017. Patients were treated with standard treatments, and oncologic results, including locoregional recurrence-free survival, distant metastasis-free survival, and overall survival (OS), were assessed over a 10-year follow-up period. Results: There was no significant difference in oncologic outcomes between two groups and based on subtypes, including hormone receptor (HR)-positive, HER2-positive, and triple-negative breast cancer (TNBC). In the HR-positive breast cancer group, the TAS and ALND groups showed very similar trends . In HER2-positive breast cancer, although not statistically significant, the survival outcomes were better in the TAS group than in the ALND group. However, the OS in the TAS group for TNBC was lower than that in the ALND group, though not significantly. Conclusions and Relevance: This study demonstrates that TAS is comparable to ALND in terms of 10-year oncological outcomes across different types of node-positive breast cancer, suggesting its potential as a viable alternative. Breast cancer Node metastasis Neoadjuvant chemotherapy Targeted axillary sampling Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction According to the NCCN guidelines, clinically node-positive breast cancer can be treated using neoadjuvant chemotherapy (NAC) 1 . Treatment responses to NAC vary according to the breast cancer subtype, with HER2-positive and triple-negative breast cancer (TNBC) exhibiting substantially higher responses than hormone-positive breast cancer 2 – 5 . Because the prognosis of patients who show a pathologic complete response (pCR) has been reported to be considerably better than that of those who show a non-pCR, the goal of NAC is to achieve a pCR for breast cancer 6 , 7 . It is essential that the primary tumor bed be pathologically evaluated to verify whether pCR has been achieved. To not miss the exact primary tumor site, various techniques have been established to track cancer and confirm that the region has been accurately excised 8 – 12 . Since 2000, the most common method for monitoring breast cancer has been placing a clip in the center of tumor 13 , 14 . After removing the breast tissue, it is essential to confirm whether the clip was successfully removed by intraoperative specimen mammography. A tattooing method using dyes such as activated charcoal has also been used for the accurate resection of breast cancer or axillary lymph nodes 15 , 16 , and marking axillary lymph nodes with the radioactive iodine 125 I Seeds (MARI) technique with placement of a radioactive seed into a positive lymph node is also one of these tracking procedures 17 – 19 . The false-negative rate of these methods has been reported to be 7–20%. In prior studies, our team validated the targeting feasibility using the activated charcoal tattooing technique or clip placement at diagnosis in patients with breast cancer who received NAC 20 , 21 . This approach was also applied to patients who underwent upfront surgery with targeted axillary surgery (TAS), and the 5-year oncological outcomes have been reported 22 . Herein, we update the oncologic outcomes with a 10-year follow-up period of patients with cT1-3N1-2 breast cancer who underwent NAC followed by TAS surgery. Materials and Methods Between 2012 and 2017, a total of 1,984 female patients with operable breast cancer who were treated at Kyungpook National University Chilgok Hospital were reviewed. All patients were diagnosed with invasive breast cancer by needle or excision biopsy, and axillary lymph node metastasis was confirmed by fine-needle aspiration cytology or needle biopsy. Breast cancer and metastatic axillary lymph nodes were assessed according to their size, location, and number based on mammography, ultrasonography, and breast magnetic resonance (MR) imaging before treatment. Patients who received upfront surgery for NAC (n = 1,572) and those who underwent sentinel lymph node biopsy after NAC (n = 125) were excluded. A total of 235 patients with cT1-3N1-2 breast cancer provided written informed consent to undergo breast surgery and axillary surgery (TAS, n = 109; ALND, n = 127), and 30 patients who underwent initial TAS and then ALND were classified into the ALND group. Finally, 78 patients were classified as the TAS group, and 157 patients were classified as the ALND group. After surgery, the standard adjuvant treatment was completed, and surveillance was performed biannually for the first 2 years and annually thereafter for a further 8 years. Routine surveillance was conducted using blood tests, tumor markers, mammography, breast ultrasonography and MR imaging, chest and abdominal CT, and bone scans (Fig. 1 ). For the TAS procedure, targeted techniques for axillary lymph nodes were conducted by ultrasound with tattooing using Charcotrace black ink (Phebra, Lane Cove West, Australia) and by clip insertion for the accurate resection of the lymph node. While 1–3 mL of Charcotrace was injected using a 23-gauge needle into the adjacent soft tissue after local anesthesia for tattooing, a clip (UltraClip® Breast Tissue Markers, BARD NJ, USA) was inserted into the center of the lymph node 20 , 21 . Whether the procedure was performed or not, the patients underwent breast-conserving surgery or mastectomy for the complete removal of the breast cancer. Axillary surgery was performed as either ALND or TAS, depending on the patients’ decision, and the final plan was determined by surgeons before and during the surgery. The patients receiving the TAS were informed that they would need to receive additional radiotherapy in the axillary region. The TAS procedure was performed by leaving sufficient soft and lymphoid tissue around the axillary vessels based on the definition of the surgical boundaries, and ALND was performed using the conventional technique 22 . The clinical variables assessed, including age at diagnosis, body mass index (BMI), type of tumor, clinical and pathologic tumor size, type of surgery, number of total and metastatic axillary lymph nodes, tumor subtypes, and additional treatments, were retrospectively reviewed based on the patient’s medical records. The molecular breast cancer subtypes were classified based on the results of immunohistochemical staining of the biopsy samples before the initial treatment as either hormone receptor (HR) positive breast cancer [either estrogen receptor (ER) or progesterone receptor (PR) is positive], HER2-positive breast cancer (ER and PR are negative; HER2 gene is positive), or TNBC (ER, PR, and HER2 are all negative). The Ki67 index was considered high when > 15% of the tumor cells showed nuclear immunoreactivity. The ASCO/CAP 2016 guidelines were followed for the histopathological examination of the four biomarkers. Statistical analysis for oncologic results was assessed using the locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) parameters using SPSS version 29.0 (SPSS, Chicago, IL, USA). For the comparison of ALND versus TAS with axillary radiotherapy, categorical or continuous variables were evaluated using the χ 2 test or Student’s t -test, and oncologic outcomes, including locoregional recurrence, distant metastasis, and death, were assessed with Kaplan-Meier analysis. P < 0.05 was defined as statistically significant. Results The mean age of the 235 patients was 48.2 years (standard deviation (SD), ± 9.7 years), and the mean BMI was 24.6 kg/m 2 (SD, ± 3.9 kg/m 2 ). The most common tumor type was invasive ductal carcinoma in both groups (TAS, 96.2%; ALND, 100.0%) (p < 0.001). Although the clinical tumor size was significantly larger in the ALND group (p = 0.003), there were no statistical differences in the clinical T stage or number of suspicious axillary lymph nodes at diagnosis (p = 0.062 and p = 0.985, respectively). Breast-conserving surgery was frequently performed in the TAS group (p < 0.001), and 10 patients in the TAS group did not receive axillary radiotherapy (Table 1 ). Table 1 Clinical characteristics of patients with breast cancer who underwent neoadjuvant chemotherapy followed by targeted axillary surgery or axillary lymph node dissection Targeted axillary surgery (n = 78) Axillary lymph node dissection (n = 157) p-value Age (mean ± SD, years) 49.2 ± 10.2 47.8 ± 9.5 0.345 Body mass index (mean ± SD, kg/m 2 ) 24.8 ± 3.8 24.5 ± 4.0 0.621 Menopausal status Pre-menopause 41 (52.6) 113 (72.0) 0.022 Post-menopause 37 (47.4) 44 (28.0) Type of tumor (n, %) Invasive ductal carcinoma 75 (96.2) 157 (100.0) < 0.001 Invasive lobular carcinoma 2 (2.6) 0 (0.0) Mixed invasive ductal and lobular carcinoma 1 (1.3) 0 (0.0) Clinical tumor size (mean ± SD, cm) 3.9 ± 1.9 5.1 ± 2.5 0.003 Clinical T stage T1 8 (10.3) 9 (5.7) 0.062 T2 54 (69.2) 96 (61.1) T3 16 (20.5) 52 (33.1) No. of suspicious axillary lymph nodes 1–3 46 (59.0) 82 (52.3) 0.985 4–9 27 (34.6) 66 (42.0) > 10 5 (6.4) 9 (5.7) Type of breast surgery (n, %) Breast-conserving surgery 31 (39.7) 11 (7.0) < 0.001 Mastectomy 47 (60.3) 146 (93.0) Regimen of neoadjuvant chemotherapy (n, %) Anthracycline/Cyclophosphamide (AC) 3 (3.8) 6 (3.8) - Sequential AC and Taxane ± Target therapy 60 (76.9) 141 (89.8) Docetaxel/Carboplatin + Target therapy 12 (15.4) 9 (5.7) Others 3 (3.8) 1 (0.6) Adjuvant chemotherapy (n, %) 1 (1.3) 3 (1.9) < 0.001 Adjuvant radiotherapy (n, %) Breast 74 (94.9) 142 (90.4) 0.119 Axillary area 68 (87.2) 41 (26.1) 0.008 Adjuvant hormonal therapy (n, %) 54 (69.2) 108 (68.8) 0.891 SD, standard deviation After NAC, the pathologic tumor size was significantly smaller in the TAS group (p < 0.001), and the pCR rate of the breast and axillary area was significantly higher in the TAS group (p < 0.001 and p < 0.002, respectively). The distribution of the breast tumor subtypes was not different between the two groups. In the TAS group, HR-positive breast cancer was present in 51 cases (65.4%), HER2-positive breast cancer in 10 cases (12.8%), and TNBC in 17 cases (21.8%). In the ALND group, HR-positive breast cancer was present in 107 cases (68.2%), HER2-positive breast cancer in 21 cases (36.8%), and TNBC was found in 29 cases (18.5%). All subtypes were not different between the two groups (Table 2 ). Table 2 Pathologic characteristics of patients with breast cancer who underwent neoadjuvant chemotherapy followed by targeted axillary surgery or axillary lymph nodes dissection Targeted axillary surgery (n = 78) Axillary lymph node dissection (n = 157) p-value Rate of pathologic complete response (pCR) (n, %) Breast 25 (32.1) 20 (12.7) < 0.001 Axillary lymph nodes 52 (66.7) 68 (43.3) 0.002 Pathologic tumor size (mean ± SD, cm) 1.0 ± 1.3 1.9 ± 2.1 < 0.001 No. of metastatic lymph nodes (mean ± SD) 1.6 ± 0.9 2.7 ± 4.6 0.021 No. of removed lymph nodes (mean ± SD) 8.5 ± 3.6 14.1 ± 8.3 < 0.001 Estrogen receptor (n, %) Positive 43 (55.1) 79 (50.3) 0.074 Negative 35 (44.9) 78 (49.7) Progesterone receptor (n, %) Positive 39 (50.0) 76 (48.4) 0.078 Negative 39 (50.0) 81 (51.6) c-erbB2 gene (n, %) Positive 27 (34.6) 50 (31.8) 0.653 Negative 51 (65.4) 107 (68.2) Triple-negative breast cancer (n, %) Positive 17 (21.8) 29 (18.5) 0.667 Negative 61 (78.2) 128 (81.5) SD, standard deviation The follow-up periods of both groups were 98.7 months (SD, ± 16.4 months) in the TAS group and 109.2 months (SD, ± 27.3 months) in the ALND group (p = 0.875). There were 25 cases (10.6%) of locoregional recurrence and 42 cases (17.9%) of distant metastasis in the patients. There was no statistical difference in the LRFS and DMFS between the TAS and ALND groups (p = 0.673 and p = 0.729, respectively). The OS was also similar in both groups (p = 0.396) (Fig. 2 ). There were 7 (9.0%) and 18 (11.5%) cases of locoregional recurrence, and 12 (15.4%) and 30 cases (19.1%) of distant metastasis in the TAS and ALND groups, respectively. In the TAS group, 15 patients (19.2%) died and 25 patients (15.9%) died during the follow-up period. All oncologic outcomes based on the breast cancer subtypes are shown in supplementary table 1 . In terms of the LRFS, DMFS, and OS, there were no statistical differences in HR-positive breast cancer (LRFS, p = 0.954; DMFS, p = 0.993; and OS, p = 0.617) and HER2-positive breast cancer (LRFS, p = 0.967; DMFS, p = 0.999; and OS, p = 0.423) (Fig. 3 , 4 ). However, the OS in the TAS group for TNBC was lower than that in the ALND group, although it was not significant (LRFS, p = 0.411; DMFS, p = 0.697; and OS, p = 0.210) (Fig. 5 ). Discussion In this study, we compared the 10-year follow-up results of patients with cT1-3N1-2 breast cancer who underwent TAS after NAC with those who underwent conventional ALND after NAC. There were no differences in the oncologic outcomes, including LRFS, DMFS, and OS, between the two groups in all of the patients. In addition, oncological outcomes showed no differences across the molecular subtypes, including HR-positive, HER2-positive, and TNBC. Initially, the primary objective of NAC in breast cancer was to achieve resectability in inoperable locally advanced or inflammatory breast cancer 23 – 25 . Furthermore, NAC allowed the use of breast-conserving surgery rather than mastectomy and enabled monitoring of the tumor response 26 – 28 . Recently, the goal of NAC in breast cancer has changed to the achievement of pCR, which is a predictive surrogate marker of a better prognosis 29 , 30 . However, to verify the pCR of breast cancer, the exact cancer tissues should be pathologically evaluated. Because of postoperative morbidities, such as lymphedema and nerve injury, the concept of partial ALND was introduced for patients with node-negative breast cancer by several surgeons 31 – 33 . However, rather than simply resecting part of the ALND, a targeting technique is required for node-positive breast cancer. To address this problem, it is important to mark the primary tumor and positive axillary lymph nodes for tracking during and after NAC. Several methods, including the placement of a clip or radioactive seed and charcoal tattooing, have been developed 8 – 12 . Although many novel techniques have been introduced, long-term oncologic outcomes remain underreported. Our team reported the 5- and 10-year oncologic outcomes of patients with node-positive breast cancer who received upfront surgery with TAS compared with those that received ALND 22 , 34 . In the serial oncological outcomes, the TAS group consistently indicated non-inferiority compared with the ALND group. Additionally, a similar trend was observed in this study focusing on patients who received prior chemotherapy. It is important to explore how TAS, a surgical technique that has not yet been standardized, can be beneficial for patients compared with the traditional ALND approach. First, by targeting the exact lesion, accurate information can be obtained to determine the tumor response after NAC in breast cancer. Although it is uncommon to miss metastasis-proven lymph nodes during conventional ALND, because the structure of lymph nodes becomes faint as they are replaced by fatty changes and fibrosis 35 – 37 , there is a possibility of this occurring. Second, the rate of lymphedema is significantly higher in patients who received ALND than in those who received TAS with axillary radiotherapy 38 . Because it is impossible to be completely cured and the quality of life deteriorates once lymphedema occurs, prevention is the most important consideration for lymphedema 39 – 41 . Third, the operative time can be reduced when TAS is applied, and there are fewer sequelae, including bleeding or paresthesia, because the blood vessels or nerve structures are relatively less exposed. In this study, the authors compared the TAS group with or without axillary radiotherapy and the ALND group in patients with node-positive breast cancer who received NAC and showed consistent oncologic outcomes across the breast cancer subtypes. Although the difference between the two groups in TNBC was somewhat increased during the 10-year follow-up period, statistical significance was lacking. This indicates that the TAS procedure can be applied to patients with N1-2 breast cancer after NAC. However, if the breast cancer is higher than N3 or has a high tumor burden in the axillary lymph nodes even after NAC, it would be better to proceed with ALND. To the best of our knowledge, this study represents a pioneering long-term oncologic report of patients with node-positive breast cancer who underwent NAC followed by TAS. Pretreatment with chemotherapy may induce lymphedema in the arms even before surgical intervention, and ALND often fails to sufficiently mitigate this condition. Consequently, TAS has emerged as a viable alternative, particularly for patients who respond positively to NAC. Despite the inherent limitations of a retrospective design and a relatively small cohort, this study underscores the potential of TAS as a standard treatment option within this patient population. Declarations Author Contributions: Conceptualization, JL, WHK, HJK and HYP; methodology, JL, HYP, and BK; validation, SJL, YSC, IHL; investigation, BK, and JHJ; clinical practice; JL, WHK, HJK, J-YP, NJP, and HYP; resources, BK; data curation, JL, JHJ, and BK; writing – original draft preparation, JL; writing, review, and editing; JL, HYP, and JHJ; visualization, JL; supervision, HYP. Institutional Review Board Statement: This study was approved by the Institutional Review Board Committee of the Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea (KNUCH 2015-05-205). In addition, specific inclusion and exclusion criteria were defined according to the approved institutional review board protocol. Informed Consent Statement: Informed consent was obtained from all the participants involved in this study. Data Availability Statement: The datasets generated and analyzed during the current study are not publicly available. However, they are available from the corresponding author upon reasonable request. Acknowledgments : Not applicable Conflicts of Interest: The authors declare no conflicts of interest. Funding : This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2014R1A5A2009242, 2022R1F1A1072458) and this research was supported by the Bio &Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2017M3A9G8083382) and this work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2022R1I1A1A01070224). This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HR22C1832). References Gradishar WJ, Moran MS, Abraham J, et al. 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Also discoverable on Platform About Our Team In Review Editorial Policies 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-5004479","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":351384041,"identity":"86c38dff-646f-47e4-bb94-900fc6ca1717","order_by":0,"name":"Jeeyeon Lee","email":"","orcid":"","institution":"Kyungpook National University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jeeyeon","middleName":"","lastName":"Lee","suffix":""},{"id":351384042,"identity":"7470c53c-f397-4d03-852f-0526d2f13e2d","order_by":1,"name":"Byeongju Kang","email":"","orcid":"","institution":"Kyungpook National University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Byeongju","middleName":"","lastName":"Kang","suffix":""},{"id":351384043,"identity":"e86cb46d-3714-4a35-b53e-3cd80acc9e36","order_by":2,"name":"Hye Jung Kim","email":"","orcid":"","institution":"Kyungpook National University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hye","middleName":"Jung","lastName":"Kim","suffix":""},{"id":351384048,"identity":"6b827b5a-b340-42d7-aa27-b27f3445888f","order_by":3,"name":"Won Hwa Kim","email":"","orcid":"","institution":"Kyungpook National University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Won","middleName":"Hwa","lastName":"Kim","suffix":""},{"id":351384051,"identity":"21dc1369-25ed-4f26-be4a-15ecdb28ecd1","order_by":4,"name":"Yee Soo Chae","email":"","orcid":"","institution":"Kyungpook National University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yee","middleName":"Soo","lastName":"Chae","suffix":""},{"id":351384053,"identity":"dea2772a-5617-4728-84fe-3a12577beaa0","order_by":5,"name":"Soo Jung Lee","email":"","orcid":"","institution":"Kyungpook National University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Soo","middleName":"Jung","lastName":"Lee","suffix":""},{"id":351384054,"identity":"a3282bd5-b293-4d24-a8f9-982d655bb767","order_by":6,"name":"In-Hee Lee","email":"","orcid":"","institution":"Kyungpook National University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"In-Hee","middleName":"","lastName":"Lee","suffix":""},{"id":351384055,"identity":"84d9c558-c8e2-4453-acc1-23667ff0d707","order_by":7,"name":"Ji-Young Park","email":"","orcid":"","institution":"Kyungpook National University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ji-Young","middleName":"","lastName":"Park","suffix":""},{"id":351384056,"identity":"ba83e3b4-32a0-4228-9aeb-0b14da381373","order_by":8,"name":"Nora Jee-Young Park","email":"","orcid":"","institution":"Kyungpook National University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nora","middleName":"Jee-Young","lastName":"Park","suffix":""},{"id":351384057,"identity":"7c100d98-dbc9-4e4f-9f55-abbcd5f013c7","order_by":9,"name":"Ho Yong Park","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYDACCQaGAx9+2BhAuQlEaWE8OLMnjTQtzId52A6ToMVcusfgAA/PeWNziQTGDz8Y0vIJarGcc8bggITFbTPLGQnMkj0MOZYNhLQY3MgxOGDAc9vG4EYCgzQDQ4UBIR0QLQls50BamH8Tr+UA2wEzoBY2oC05hLVYzkgrONjYk2xscOZhm2WPQRphLeYSyZs///lhZ7jhePLhGz8qkolwGAMHTBFjA4hLGBgwsD8gQtkoGAWjYBSMaAAAZUc9bwasS2QAAAAASUVORK5CYII=","orcid":"","institution":"Kyungpook National University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ho","middleName":"Yong","lastName":"Park","suffix":""}],"badges":[],"createdAt":"2024-08-30 14:12:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5004479/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5004479/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":67111240,"identity":"548335a4-f288-4cd4-849b-69ee14fb2090","added_by":"auto","created_at":"2024-10-21 09:42:52","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":734920,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the comparison between targeted axillary surgery (TAS) and conventional axillary lymph node dissection (ALND) in patients with node-positive breast cancer who were treated with neoadjuvant chemotherapy followed by surgery and adjuvant treatment.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5004479/v1/9b52fa5c0e2c23bb0bb18f80.jpg"},{"id":67111684,"identity":"8d4cf84c-bb27-4426-be82-57f7dbf32dbf","added_by":"auto","created_at":"2024-10-21 09:50:52","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":349829,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival outcomes of patients with node-positive breast cancer that were treated with neoadjuvant chemotherapy followed by surgery and adjuvant treatment. The 10-year locoregional recurrence-free survival (A), distant metastasis-free survival (B), and overall survival (C) in the targeted axillary surgery group and axillary lymph node dissection group were analyzed.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5004479/v1/ccd7dad293a97064f3c05134.jpg"},{"id":67111686,"identity":"6344163e-32d5-400b-80f7-0de8654c5bdb","added_by":"auto","created_at":"2024-10-21 09:50:52","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":349807,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival outcomes of node-positive breast cancer which were treated with neoadjuvant chemotherapy followed by surgery and adjuvant treatments in hormone receptor-positive breast cancer patients. Locoregional recurrence-free survival (A), distant metastasis-free survival (B), and overall survival (C) outcomes of patients with hormone receptor-positive breast cancer.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5004479/v1/eb8b12b9ddcb102b1b3317da.jpg"},{"id":67111245,"identity":"9fe585ce-7dab-410c-bbb2-83f2b1657d79","added_by":"auto","created_at":"2024-10-21 09:42:53","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":348921,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival outcomes of node-positive breast cancer which were treated with neoadjuvant chemotherapy followed by surgery and adjuvant treatments in HER2-positive breast cancer patients. Locoregional recurrence-free survival (A), distant metastasis-free survival (B), and overall survival (C) outcomes of patients with HER2-positive breast cancer.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5004479/v1/e767a6cb93e7ad85192d7b08.jpg"},{"id":67113146,"identity":"111f9d81-7771-46c3-a7d1-120a08edaac0","added_by":"auto","created_at":"2024-10-21 09:58:52","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":353110,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival outcomes of node-positive breast cancer which were treated with neoadjuvant chemotherapy followed by surgery and adjuvant treatments in triple-negative breast cancer patients. Locoregional recurrence-free survival (A), distant metastasis-free survival (B), and overall survival (C) outcomes of patients with triple-negative breast cancer.\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5004479/v1/c0d72c164f8594f344e79e9c.jpg"},{"id":99679656,"identity":"08d3962e-523f-442c-af03-57fee0e60cf0","added_by":"auto","created_at":"2026-01-07 08:40:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2705586,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5004479/v1/110619ab-030c-4463-a17c-7c05cef51201.pdf"},{"id":67111241,"identity":"cfd158fe-a5e3-41e5-aaf8-c3dc0c13bbf8","added_by":"auto","created_at":"2024-10-21 09:42:52","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17128,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable.docx","url":"https://assets-eu.researchsquare.com/files/rs-5004479/v1/f21fd87a8afb140a5d01716d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"10-Year Outcomes of Targeted Axillary Surgery after Neoadjuvant Chemotherapy in Breast Cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to the NCCN guidelines, clinically node-positive breast cancer can be treated using neoadjuvant chemotherapy (NAC)\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Treatment responses to NAC vary according to the breast cancer subtype, with HER2-positive and triple-negative breast cancer (TNBC) exhibiting substantially higher responses than hormone-positive breast cancer\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Because the prognosis of patients who show a pathologic complete response (pCR) has been reported to be considerably better than that of those who show a non-pCR, the goal of NAC is to achieve a pCR for breast cancer\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt is essential that the primary tumor bed be pathologically evaluated to verify whether pCR has been achieved. To not miss the exact primary tumor site, various techniques have been established to track cancer and confirm that the region has been accurately excised\u003csup\u003e\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Since 2000, the most common method for monitoring breast cancer has been placing a clip in the center of tumor\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. After removing the breast tissue, it is essential to confirm whether the clip was successfully removed by intraoperative specimen mammography. A tattooing method using dyes such as activated charcoal has also been used for the accurate resection of breast cancer or axillary lymph nodes\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, and marking axillary lymph nodes with the radioactive iodine \u003csup\u003e125\u003c/sup\u003eI Seeds (MARI) technique with placement of a radioactive seed into a positive lymph node is also one of these tracking procedures\u003csup\u003e\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. The false-negative rate of these methods has been reported to be 7\u0026ndash;20%.\u003c/p\u003e \u003cp\u003eIn prior studies, our team validated the targeting feasibility using the activated charcoal tattooing technique or clip placement at diagnosis in patients with breast cancer who received NAC\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. This approach was also applied to patients who underwent upfront surgery with targeted axillary surgery (TAS), and the 5-year oncological outcomes have been reported\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Herein, we update the oncologic outcomes with a 10-year follow-up period of patients with cT1-3N1-2 breast cancer who underwent NAC followed by TAS surgery.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e Between 2012 and 2017, a total of 1,984 female patients with operable breast cancer who were treated at Kyungpook National University Chilgok Hospital were reviewed. All patients were diagnosed with invasive breast cancer by needle or excision biopsy, and axillary lymph node metastasis was confirmed by fine-needle aspiration cytology or needle biopsy. Breast cancer and metastatic axillary lymph nodes were assessed according to their size, location, and number based on mammography, ultrasonography, and breast magnetic resonance (MR) imaging before treatment. Patients who received upfront surgery for NAC (n\u0026thinsp;=\u0026thinsp;1,572) and those who underwent sentinel lymph node biopsy after NAC (n\u0026thinsp;=\u0026thinsp;125) were excluded. A total of 235 patients with cT1-3N1-2 breast cancer provided written informed consent to undergo breast surgery and axillary surgery (TAS, n\u0026thinsp;=\u0026thinsp;109; ALND, n\u0026thinsp;=\u0026thinsp;127), and 30 patients who underwent initial TAS and then ALND were classified into the ALND group. Finally, 78 patients were classified as the TAS group, and 157 patients were classified as the ALND group. After surgery, the standard adjuvant treatment was completed, and surveillance was performed biannually for the first 2 years and annually thereafter for a further 8 years. Routine surveillance was conducted using blood tests, tumor markers, mammography, breast ultrasonography and MR imaging, chest and abdominal CT, and bone scans (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor the TAS procedure, targeted techniques for axillary lymph nodes were conducted by ultrasound with tattooing using Charcotrace black ink (Phebra, Lane Cove West, Australia) and by clip insertion for the accurate resection of the lymph node. While 1\u0026ndash;3 mL of Charcotrace was injected using a 23-gauge needle into the adjacent soft tissue after local anesthesia for tattooing, a clip (UltraClip\u0026reg; Breast Tissue Markers, BARD NJ, USA) was inserted into the center of the lymph node\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Whether the procedure was performed or not, the patients underwent breast-conserving surgery or mastectomy for the complete removal of the breast cancer. Axillary surgery was performed as either ALND or TAS, depending on the patients\u0026rsquo; decision, and the final plan was determined by surgeons before and during the surgery. The patients receiving the TAS were informed that they would need to receive additional radiotherapy in the axillary region. The TAS procedure was performed by leaving sufficient soft and lymphoid tissue around the axillary vessels based on the definition of the surgical boundaries, and ALND was performed using the conventional technique\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe clinical variables assessed, including age at diagnosis, body mass index (BMI), type of tumor, clinical and pathologic tumor size, type of surgery, number of total and metastatic axillary lymph nodes, tumor subtypes, and additional treatments, were retrospectively reviewed based on the patient\u0026rsquo;s medical records. The molecular breast cancer subtypes were classified based on the results of immunohistochemical staining of the biopsy samples before the initial treatment as either hormone receptor (HR) positive breast cancer [either estrogen receptor (ER) or progesterone receptor (PR) is positive], HER2-positive breast cancer (ER and PR are negative; HER2 gene is positive), or TNBC (ER, PR, and HER2 are all negative). The Ki67 index was considered high when \u0026gt;\u0026thinsp;15% of the tumor cells showed nuclear immunoreactivity. The ASCO/CAP 2016 guidelines were followed for the histopathological examination of the four biomarkers.\u003c/p\u003e \u003cp\u003eStatistical analysis for oncologic results was assessed using the locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) parameters using SPSS version 29.0 (SPSS, Chicago, IL, USA). For the comparison of ALND versus TAS with axillary radiotherapy, categorical or continuous variables were evaluated using the χ\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e test or Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test, and oncologic outcomes, including locoregional recurrence, distant metastasis, and death, were assessed with Kaplan-Meier analysis. \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was defined as statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe mean age of the 235 patients was 48.2 years (standard deviation (SD), \u0026plusmn;\u0026thinsp;9.7 years), and the mean BMI was 24.6 kg/m\u003csup\u003e2\u003c/sup\u003e (SD, \u0026plusmn;\u0026thinsp;3.9 kg/m\u003csup\u003e2\u003c/sup\u003e). The most common tumor type was invasive ductal carcinoma in both groups (TAS, 96.2%; ALND, 100.0%) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Although the clinical tumor size was significantly larger in the ALND group (p\u0026thinsp;=\u0026thinsp;0.003), there were no statistical differences in the clinical T stage or number of suspicious axillary lymph nodes at diagnosis (p\u0026thinsp;=\u0026thinsp;0.062 and p\u0026thinsp;=\u0026thinsp;0.985, respectively). Breast-conserving surgery was frequently performed in the TAS group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and 10 patients in the TAS group did not receive axillary radiotherapy (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of patients with breast cancer who underwent neoadjuvant chemotherapy followed by targeted axillary surgery or axillary lymph node dissection\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTargeted axillary surgery (n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAxillary lymph node dissection (n\u0026thinsp;=\u0026thinsp;157)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.621\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMenopausal status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePre-menopause\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e113 (72.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePost-menopause\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (47.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of tumor (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (96.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e157 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInvasive lobular carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMixed invasive ductal and lobular carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical tumor size (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical T stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (69.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96 (61.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52 (33.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of suspicious axillary lymph nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (59.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82 (52.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.985\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u0026ndash;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (34.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66 (42.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of breast surgery (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBreast-conserving surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (39.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMastectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 (60.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e146 (93.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegimen of neoadjuvant chemotherapy (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnthracycline/Cyclophosphamide (AC)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSequential AC and Taxane\u0026thinsp;\u0026plusmn;\u0026thinsp;Target therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (76.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e141 (89.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDocetaxel/Carboplatin\u0026thinsp;+\u0026thinsp;Target therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant chemotherapy (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant radiotherapy (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBreast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (94.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e142 (90.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.119\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAxillary area\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (87.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (26.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant hormonal therapy (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (69.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e108 (68.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.891\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eSD, standard deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAfter NAC, the pathologic tumor size was significantly smaller in the TAS group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and the pCR rate of the breast and axillary area was significantly higher in the TAS group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 and p\u0026thinsp;\u0026lt;\u0026thinsp;0.002, respectively). The distribution of the breast tumor subtypes was not different between the two groups. In the TAS group, HR-positive breast cancer was present in 51 cases (65.4%), HER2-positive breast cancer in 10 cases (12.8%), and TNBC in 17 cases (21.8%). In the ALND group, HR-positive breast cancer was present in 107 cases (68.2%), HER2-positive breast cancer in 21 cases (36.8%), and TNBC was found in 29 cases (18.5%). All subtypes were not different between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePathologic characteristics of patients with breast cancer who underwent neoadjuvant chemotherapy followed by targeted axillary surgery or axillary lymph nodes dissection\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTargeted axillary surgery (n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAxillary lymph node dissection (n\u0026thinsp;=\u0026thinsp;157)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRate of pathologic complete response (pCR) (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBreast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25 (32.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAxillary lymph nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e68 (43.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathologic tumor size (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of metastatic lymph nodes (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of removed lymph nodes (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEstrogen receptor (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43 (55.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e79 (50.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.074\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (44.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e78 (49.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgesterone receptor (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e76 (48.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e81 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ec-erbB2 gene (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27 (34.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.653\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51 (65.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e107 (68.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTriple-negative breast cancer (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (21.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e29 (18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.667\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61 (78.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e128 (81.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eSD, standard deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe follow-up periods of both groups were 98.7 months (SD, \u0026plusmn;\u0026thinsp;16.4 months) in the TAS group and 109.2 months (SD, \u0026plusmn;\u0026thinsp;27.3 months) in the ALND group (p\u0026thinsp;=\u0026thinsp;0.875). There were 25 cases (10.6%) of locoregional recurrence and 42 cases (17.9%) of distant metastasis in the patients. There was no statistical difference in the LRFS and DMFS between the TAS and ALND groups (p\u0026thinsp;=\u0026thinsp;0.673 and p\u0026thinsp;=\u0026thinsp;0.729, respectively). The OS was also similar in both groups (p\u0026thinsp;=\u0026thinsp;0.396) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There were 7 (9.0%) and 18 (11.5%) cases of locoregional recurrence, and 12 (15.4%) and 30 cases (19.1%) of distant metastasis in the TAS and ALND groups, respectively. In the TAS group, 15 patients (19.2%) died and 25 patients (15.9%) died during the follow-up period. All oncologic outcomes based on the breast cancer subtypes are shown in supplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In terms of the LRFS, DMFS, and OS, there were no statistical differences in HR-positive breast cancer (LRFS, p\u0026thinsp;=\u0026thinsp;0.954; DMFS, p\u0026thinsp;=\u0026thinsp;0.993; and OS, p\u0026thinsp;=\u0026thinsp;0.617) and HER2-positive breast cancer (LRFS, p\u0026thinsp;=\u0026thinsp;0.967; DMFS, p\u0026thinsp;=\u0026thinsp;0.999; and OS, p\u0026thinsp;=\u0026thinsp;0.423) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e,\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). However, the OS in the TAS group for TNBC was lower than that in the ALND group, although it was not significant (LRFS, p\u0026thinsp;=\u0026thinsp;0.411; DMFS, p\u0026thinsp;=\u0026thinsp;0.697; and OS, p\u0026thinsp;=\u0026thinsp;0.210) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eIn this study, we compared the 10-year follow-up results of patients with cT1-3N1-2 breast cancer who underwent TAS after NAC with those who underwent conventional ALND after NAC. There were no differences in the oncologic outcomes, including LRFS, DMFS, and OS, between the two groups in all of the patients. In addition, oncological outcomes showed no differences across the molecular subtypes, including HR-positive, HER2-positive, and TNBC.\u003c/p\u003e \u003cp\u003eInitially, the primary objective of NAC in breast cancer was to achieve resectability in inoperable locally advanced or inflammatory breast cancer\u003csup\u003e\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Furthermore, NAC allowed the use of breast-conserving surgery rather than mastectomy and enabled monitoring of the tumor response\u003csup\u003e\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Recently, the goal of NAC in breast cancer has changed to the achievement of pCR, which is a predictive surrogate marker of a better prognosis\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. However, to verify the pCR of breast cancer, the exact cancer tissues should be pathologically evaluated.\u003c/p\u003e \u003cp\u003eBecause of postoperative morbidities, such as lymphedema and nerve injury, the concept of partial ALND was introduced for patients with node-negative breast cancer by several surgeons\u003csup\u003e\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. However, rather than simply resecting part of the ALND, a targeting technique is required for node-positive breast cancer. To address this problem, it is important to mark the primary tumor and positive axillary lymph nodes for tracking during and after NAC. Several methods, including the placement of a clip or radioactive seed and charcoal tattooing, have been developed\u003csup\u003e\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Although many novel techniques have been introduced, long-term oncologic outcomes remain underreported.\u003c/p\u003e \u003cp\u003eOur team reported the 5- and 10-year oncologic outcomes of patients with node-positive breast cancer who received upfront surgery with TAS compared with those that received ALND\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. In the serial oncological outcomes, the TAS group consistently indicated non-inferiority compared with the ALND group. Additionally, a similar trend was observed in this study focusing on patients who received prior chemotherapy.\u003c/p\u003e \u003cp\u003eIt is important to explore how TAS, a surgical technique that has not yet been standardized, can be beneficial for patients compared with the traditional ALND approach. First, by targeting the exact lesion, accurate information can be obtained to determine the tumor response after NAC in breast cancer. Although it is uncommon to miss metastasis-proven lymph nodes during conventional ALND, because the structure of lymph nodes becomes faint as they are replaced by fatty changes and fibrosis\u003csup\u003e\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e, there is a possibility of this occurring. Second, the rate of lymphedema is significantly higher in patients who received ALND than in those who received TAS with axillary radiotherapy\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. Because it is impossible to be completely cured and the quality of life deteriorates once lymphedema occurs, prevention is the most important consideration for lymphedema\u003csup\u003e\u003cspan additionalcitationids=\"CR40\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Third, the operative time can be reduced when TAS is applied, and there are fewer sequelae, including bleeding or paresthesia, because the blood vessels or nerve structures are relatively less exposed.\u003c/p\u003e \u003cp\u003eIn this study, the authors compared the TAS group with or without axillary radiotherapy and the ALND group in patients with node-positive breast cancer who received NAC and showed consistent oncologic outcomes across the breast cancer subtypes. Although the difference between the two groups in TNBC was somewhat increased during the 10-year follow-up period, statistical significance was lacking. This indicates that the TAS procedure can be applied to patients with N1-2 breast cancer after NAC. However, if the breast cancer is higher than N3 or has a high tumor burden in the axillary lymph nodes even after NAC, it would be better to proceed with ALND.\u003c/p\u003e \u003cp\u003e To the best of our knowledge, this study represents a pioneering long-term oncologic report of patients with node-positive breast cancer who underwent NAC followed by TAS. Pretreatment with chemotherapy may induce lymphedema in the arms even before surgical intervention, and ALND often fails to sufficiently mitigate this condition. Consequently, TAS has emerged as a viable alternative, particularly for patients who respond positively to NAC. Despite the inherent limitations of a retrospective design and a relatively small cohort, this study underscores the potential of TAS as a standard treatment option within this patient population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eAuthor\u0026nbsp;\u003c/em\u003e\u003cem\u003eContributions:\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConceptualization, JL, WHK, HJK and HYP; methodology, JL, HYP, and BK; validation, SJL, YSC, IHL; investigation, BK, and JHJ; clinical practice;\u0026nbsp;JL, WHK, HJK, J-YP, NJP, and HYP; resources, BK; data curation, JL, JHJ, and BK; writing – original draft preparation, JL; writing, review, and editing;\u0026nbsp;JL, HYP, and JHJ; visualization, JL; supervision, HYP.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInstitutional\u0026nbsp;\u003c/em\u003e\u003cem\u003eReview Board Statement:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board\u0026nbsp;Committee of the\u0026nbsp;Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea (KNUCH 2015-05-205). In addition, specific inclusion and exclusion criteria were defined according to the approved institutional review board protocol.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInformed Consent Statement:\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all\u0026nbsp;the participants involved in this study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData\u0026nbsp;\u003c/em\u003e\u003cem\u003eAvailability Statement:\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed\u0026nbsp;during\u0026nbsp;the current study are not publicly available. However, they are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgments\u003c/em\u003e\u003cem\u003e:\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConflicts of\u0026nbsp;\u003c/em\u003e\u003cem\u003eInterest:\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003cem\u003e:\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2014R1A5A2009242, 2022R1F1A1072458) and this research was supported by the Bio \u0026amp;Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science \u0026amp; ICT (2017M3A9G8083382) and this work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2022R1I1A1A01070224). This research was supported by a grant of the Korea Health Technology R\u0026amp;D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health \u0026amp; Welfare, Republic of Korea (HR22C1832).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGradishar WJ, Moran MS, Abraham J, et al. Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw Jun. 2022;20(6):691\u0026ndash;722.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaque W, Verma V, Hatch S, Suzanne Klimberg V, Brian Butler E, Teh BS. Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy. Breast Cancer Res Treat Aug. 2018;170(3):559\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoussami N, Macaskill P, von Minckwitz G, Marinovich ML, Mamounas E. 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Oncol Lett Mar. 2020;19(3):2085\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\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":"Breast cancer, Node metastasis, Neoadjuvant chemotherapy, Targeted axillary sampling","lastPublishedDoi":"10.21203/rs.3.rs-5004479/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5004479/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: When pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is achieved, identifying traces of the previous tumor site or lymph nodes and performing accurate surgery becomes challenging. We conducted ultrasound-guided targeted axillary surgery (TAS) in patients with node-positive breast cancer treated with NAC. Survival outcomes were compared with those of patients who underwent conventional axillary lymph node dissection (ALND).\u003c/p\u003e\n\u003cp\u003eMethods: We conducted a retrospective analysis of 235 patients (TAS, n=78; ALND, n=157) with cT1-3N1-2 breast cancer who underwent NAC followed by surgery from 2012 to 2017. Patients were treated with standard treatments, and oncologic results, including locoregional recurrence-free survival, distant metastasis-free survival, and overall survival (OS), were assessed over a 10-year follow-up period.\u003c/p\u003e\n\u003cp\u003eResults: There was no significant difference in oncologic outcomes between two groups and based on subtypes, including hormone receptor (HR)-positive, HER2-positive, and triple-negative breast cancer (TNBC). In the HR-positive breast cancer group, the TAS and ALND groups showed very similar trends . In HER2-positive breast cancer, although not statistically significant, the survival outcomes were better in the TAS group than in the ALND group. However, the OS in the TAS group for TNBC was lower than that in the ALND group, though not significantly.\u003c/p\u003e\n\u003cp\u003eConclusions and Relevance: This study demonstrates that TAS is comparable to ALND in terms of 10-year oncological outcomes across different types of node-positive breast cancer, suggesting its potential as a viable alternative.\u003c/p\u003e","manuscriptTitle":"10-Year Outcomes of Targeted Axillary Surgery after Neoadjuvant Chemotherapy in Breast Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-21 09:42:47","doi":"10.21203/rs.3.rs-5004479/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":"7af4afa3-31d9-45f9-b210-ce2d7cbe3c04","owner":[],"postedDate":"October 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-07T08:40:21+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-21 09:42:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5004479","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5004479","identity":"rs-5004479","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}