Survival Impact of Adjuvant Capecitabine In Triple-Negative Breast Cancer Patients with Residual Disease: A Real-World Study

Survival Impact of Adjuvant Capecitabine In Triple-Negative Breast Cancer Patients with Residual Disease: A Real-World Study | 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 Survival Impact of Adjuvant Capecitabine In Triple-Negative Breast Cancer Patients with Residual Disease: A Real-World Study Noiver Graciano, Lucelly López, Carlos A. Rodriguez, Katherine Montoya, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6951831/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Sep, 2025 Read the published version in Breast Cancer Research and Treatment → Version 1 posted 11 You are reading this latest preprint version Abstract Purpose Patients with triple-negative breast cancer (TNBC) who do not achieve pathological complete response (non-pCR) after neoadjuvant chemotherapy (NACT) have a high risk of relapse. While adjuvant capecitabine (AdjCape) has demonstrated improved overall survival (OS) and disease-free survival (DFS) in Asian populations, its effectiveness in non-Asian settings remains uncertain. We aimed to evaluate the effect of AdjCape on survival outcomes using real-world data from a Latin American population. Methods We conducted a retrospective cohort study (2008–2024) including 360 women with non-metastatic TNBC and non-pCR treated at a single institution. Propensity score matching (PSM) was applied to adjust for baseline differences. Cox regression models assessed the association of AdjCape with OS and DFS, and stratified analyses identified subgroups with differential treatment effects. Results Among 360 patients, 106 (29.4%) received AdjCape. After PSM, 187 patients (72 AdjCape, 115 controls) were analyzed. AdjCape was not associated with improved OS (HR 0.79, 95% CI 0.51–1.23, p = 0.302) or DFS (HR 0.81, 95% CI 0.53–1.23, p = 0.321). However, significant benefit was observed in patients with high residual tumor burden (pT3–pT4: OS HR 0.29, p = 0.020; DFS HR 0.37, p = 0.044) and in those not receiving radiotherapy (DFS HR 0.47, p = 0.038). Conclusions AdjCape did not improve OS or DFS in the overall TNBC non-pCR cohort but may offer benefit in patients with extensive residual disease or those not treated with radiotherapy. These findings highlight the need for individualized treatment strategies and further evaluation of capecitabine in the context of modern therapies. triple-negative breast cancer adjuvant capecitabine residual disease survival real-world evidence propensity score Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, with the poorest prognosis among women with operable disease [ 1 ]. The subgroup of patients who fail to achieve pathological complete response (non-pCR) after neoadjuvant chemotherapy (NACT) accounts for the majority of breast cancer-related deaths in this population [ 2 ], and therapeutic options to improve outcomes remain limited. The CREATE-X trial demonstrated that adjuvant capecitabine (AdjCape) significantly improved 5-year overall survival (OS) and disease-free survival (DFS) in Asian patients with non-pCR, with absolute benefits of 5.6% and 6.5%, respectively [ 3 ]. However, differences in baseline prognosis, drug metabolism, and treatment tolerance between Asian and non-Asian populations have raised questions about the generalizability of these findings [ 4 – 6 ]. Recent integration of platinum-based agents and immunotherapy (e.g., pembrolizumab) into NACT regimens—therapies not included in earlier AdjCape studies—has altered the landscape of residual disease, potentially modifying both the biological profile and treatment responsiveness. Moreover, the efficacy of capecitabine in specific molecular subtypes, such as basal-like tumors or BRCA1/2 mutation carriers, remains uncertain, particularly as olaparib has shown superior outcomes in these settings [ 7 – 9 ]. In the absence of clear guidelines for post-NACT management in TNBC non-pCR, questions remain regarding the optimal sequencing, combination, or de-escalation of adjuvant therapies [ 10 ]. Evaluating the efficacy of AdjCape in broader populations and identifying patients most likely to benefit is therefore essential. Real-world evidence (RWE) provides critical insights where randomized controlled trials are limited or unfeasible, enabling the assessment of treatment effects, toxicity profiles, and external validity in heterogeneous clinical contexts [ 11 ]. This study aimed to evaluate the impact of AdjCape on OS and DFS in a real-world cohort of non-metastatic TNBC patients with non-pCR, adjusting for potential confounders using propensity score methods. METHODS Study Design, Population, and Data Collection This retrospective cohort study was conducted at the Instituto de Cancerología, Clínica Las Américas–AUNA (IDCLA-AUNA) in Medellín, Colombia, and included all women diagnosed with de novo non-metastatic triple-negative breast cancer (TNBC) between January 1, 2008, and December 31, 2024. Eligible patients received at least one cycle of neoadjuvant chemotherapy (NACT), underwent definitive surgery, and had a non-complete pathological response (non-pCR) on final pathology. Pathologic complete response (pCR) was defined as the absence of residual invasive carcinoma in the breast and axillary nodes, allowing for residual ductal carcinoma in situ (ypT0/is/ypN0) [ 12 ]. TNBC status was confirmed by institutional pathologists and defined by the absence of estrogen receptors (positivity < 1%) and HER2 negativity (IHC score of 0 or 1+, or 2 + with negative FISH). HER2 low was defined as IHC 1 + or 2 + with negative FISH; HER2 null was IHC 0. Patients were excluded if they had incomplete clinical or histopathological data, a history of synchronous or metachronous breast cancer, other malignancies (except basal or squamous cell skin cancers), or had not provided informed consent for research use of their medical records. Collected demographic and clinical data included: age, health insurance type (contributory or subsidized), comorbidities (diabetes, hypertension), parity, menopausal status, family history of breast cancer, and body mass index (BMI). Tumor-related variables included imaging modality at diagnosis, histological subtype, histological grade (HG), HER2 low status, and presence of lymphovascular invasion (LVI). HG was classified using Scarff-Bloom-Richardson criteria; histology and LVI were categorized per WHO and CAP guidelines [ 13 ]. Staging followed the 8th edition of the AJCC classification. Surgical approach (mastectomy vs. breast-conserving surgery) was determined by the treating surgeon, with preference for conserving surgery when negative margins were achievable. NACT regimens primarily consisted of anthracyclines, cyclophosphamide, and taxanes; carboplatin was introduced from 2017. For patients ineligible for anthracyclines, CMF (cyclophosphamide, methotrexate, 5-fluorouracil) or taxane-based regimens were used. Chemotherapy continued for up to six months or until dose-limiting toxicity occurred. Pembrolizumab and olaparib were not available during the study period. Radiotherapy (RT) was prescribed based on standard indications, including breast-conserving surgery, positive margins, nodal involvement, or tumor size > 5 cm in mastectomy cases. Multidisciplinary tumor boards evaluated cases with treatment ambiguity. Data were extracted from the institutional REDCap-based Breast Cancer Module, which includes prospectively recorded clinical records. Any inconsistencies were verified against original medical records. The study was approved by the Institutional Ethics Committee (Act 220–2024) and conducted in accordance with the Declaration of Helsinki and Colombian Ministry of Health resolution 8430 of 1993. Exposures and Outcomes The primary exposure was the use of adjuvant capecitabine (AdjCape), administered following surgery or after completion of RT when indicated. The treatment regimen consisted of 1000 mg/m 2 bid orally on days 1–14 of a 21-day cycle for 6–8 cycles. Dose adjustments were made for toxicity. The primary endpoint was overall survival (OS), defined as time from curative-intent surgery to death from any cause or last contact. The secondary endpoint was disease-free survival (DFS), defined as time from surgery to recurrence (local or distant), contralateral breast cancer, death, or last contact. Outcomes were defined using the STEEP version 2.0 criteria [ 14 ], with mortality verified through Colombia’s national civil registry as of March 15, 2025. Data Analysis Descriptive statistics were used to characterize the cohort. Continuous variables were summarized using mean ± SD or median with interquartile range (IQR), based on the Shapiro-Wilk test for normality. Categorical variables were reported as frequencies and percentages. To reduce treatment selection bias, 2:1 propensity score matching (PSM) was applied using a nearest neighbor method with a caliper of 0.1. Matching was based on pre-treatment variables: age, health insurance, family history, clinical stage, BMI, histological grade, LVI, HER2 low status, surgery type, and use of anthracyclines, carboplatin, and RT. Survival analysis was conducted using Kaplan–Meier estimates and log-rank tests. Cox proportional hazards models were constructed for variables with p ≤ 0.1 in univariate analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and the proportional hazards assumption was verified. Pre-specified subgroup analyses were performed for HER2 status (low vs. null), pathological tumor size (pT1–pT2 vs. pT3–pT4), and RT use to explore heterogeneity in treatment effect. All analyses were conducted using R version 4.4.2 and Jamovi version 2.6.44, with the MatchIt, Matching, cobalt, psych, survival, and survminer packages. RESULTS Clinical and Tumor Characteristics at Diagnosis and Treatment Between 2008 and 2024, 744 patients with non-metastatic triple-negative breast cancer (TNBC) were identified at the study center. Among them, 556 (74.7%) received neoadjuvant chemotherapy (NACT), and 360 (65%) exhibited residual invasive disease (non-pCR) and met the eligibility criteria. Of these, 106 patients (29.4%) received adjuvant capecitabine (AdjCape) (Fig. 1 ). In the overall cohort, the most frequent age group was 51–70 years (47%). Most patients were postmenopausal (64%) and had children (82%), with a high prevalence of overweight (41%) and obesity (23%). Approximately half of the cohort presented with stage III disease at diagnosis. Advanced primary tumor size (T3–T4) and nodal involvement were present in 51% and 61% of cases, respectively. Histologically, 90% of tumors were ductal, 76% had high histologic grade (HG), and 20% showed lymphovascular invasion (LVI). HER2 low expression, high residual tumor burden (pT3–pT4), and high nodal stage (pN2–pN3) were each observed in about 20% of patients. Regarding treatment, 63% underwent mastectomy, 69% received radiotherapy (RT), and 70% were treated with anthracyclines. Carboplatin was used in 31% of cases. Among patients receiving AdjCape, 36.8% completed fewer than six cycles, primarily due to intolerance; progression accounted for seven discontinuations. Compared to controls, the AdjCape group included a higher proportion of patients aged < 35 years (19% vs. 10%), with a family history of breast cancer (48% vs. 28%) and low-grade tumors (HG 1–2: 31.6% vs. 21.5%). In contrast, the control group had more patients with T4 tumors (28% vs. 18%) and HER2 low status (30% vs. 15%). No significant differences were found in clinical stage or residual tumor burden. The control group had higher anthracycline use (79% vs. 49%) and lower carboplatin use (19% vs. 60%). RT and surgical approach were balanced between groups (Table 1 ). Table 1 Characteristics of Patients with TNBC According to Capecitabine Use and Matching with Propensity Score VARIABLE Total N(%) = 360 AdjCape N(%) = 106 No AdjCape N(%) = 254 P AdjCape N(%) = 72 No AdjCape N(%) = 115 P Unmatched cohort PS-matched cohort Age in years (IQR) 53 (44, 63) 52 (42, 61) 54 (45, 63) 0.15 54 (45, 63) 53 (43, 62) 0.53 Categorized age (years) 0.10 0.76 70 32 (8.9) 11 (10) 21 (8.3) 9 (7.8%) 5 (6.9%) Health insurance < 0.01 0.42 Contributory 309 (86) 100 (94) 209 (82) 103 (90%) 67 (93%) Subsidized 51 (14) 6 (5.7) 45 (18) 12 (10%) 5 (6.9%) FH of breast cancer 123 (34) 51 (48) 72 (28) < 0.01 42 (37%) 29 (40%) 0.61 Menopause 230 (64) 65 (61) 165 (65) 0.51 40 (35%) 26 (36%) 0.85 Diabetes mellitus 33 (9.2) 6 (5.7) 27 (11) 0.14 9 (7.8%) 6 (8.3%) 0.90 Hypertension 128 (36) 28 (26) 100 (39) 0.02 39 (34%) 21 (29%) 0.50 Children 294 (82) 21 (20) 45 (18) 0.64 23 (20%) 14 (19%) 0.93 BMI 0.35 0.91 Normal 130 (36) 34 (32) 96 (38) 43 (37%) 25 (35%) Overweight 149 (41) 50 (47) 99 (39) 46 (40%) 31 (43%) Obese 81 (23) 22 (21) 59 (23) 26 (23%) 16 (22%) Image 0.46 0.29 Mammography 248 (69) 76 (72) 172 (68) 78 (68%) 54 (75%) Ultrasound/MRI 112 (31) 30 (28) 82 (32) 37 (32%) 18 (25%) Tumoral stage 0.23 0.91 I 15 (4.2) 7 (6.6) 8 (3.1) 5 (4.3%) 4 (5.6%) II 169 (47) 52 (49) 117 (46) 57 (50%) 34 (47%) III 51% 47 (44) 129 (51) 53 (46%) 34 (47%) cT 0.06 0.83 1 27 (7.5) 12 (11) 15 (5.9) 9 (7.8%) 7 (9.7%) 2 151 (42) 43 (41) 108 (43) 50 (43%) 31 (43%) 3 92 (26) 32 (30) 60 (24) 28 (24%) 20 (28%) 4 90 (25) 19 (18) 71 (28) 28 (24%) 14 (19%) cN 0.14 0.56 0 141 (39) 50 (47) 91 (36) 44 (38%) 34 (47%) 1 138 (38) 33 (31) 105 (41) 45 (39%) 22 (31%) 2 69 (19) 21 (20) 48 (19) 23 (20%) 15 (21%) 3 12 (3.3) 2 (1.9) 10 (3.9) 3 (2.6%) 1 (1.4%) Histology 0.35 0.88 Ductal 324 (90) 93 (88) 231 (91) 103 (90%) 65 (90%) No ductal 36 (10) 13 (12) 23 (9.1) 12 (10%) 7 (9.7%) HG 0.08 0.84 1 12 (3.3) 3 (2.8) 9 (3.5) 4 (3.5%) 3 (4.2%) 2 75 (21) 30 (28) 45 (18) 25 (22%) 18 (25%) 3 273 (76) 73 (69) 200 (79) 86 (75%) 51 (71%) LVI 73 (20) 22 (21) 51 (20) 0.88 28 (24%) 16 (22%) 0.74 HER2 < 0.01 0.42 0 291 (81%) 217 (85%) 74 (70%) 92 (80%) 54 (75%) Low 69 (19%) 37 (15%) 32 (30%) 23 (20%) 18 (25%) pT 0.78 0.99 0 23 (6.4) 7 (6.6) 16 (6.3) 6 (5.2%) 5 (6.9%) 1 174 (48) 52 (49) 122 (48) 56 (49%) 33 (46%) 2 92 (26) 24 (23) 68 (27) 30 (26%) 20 (28%) 3 47 (13) 17 (16) 30 (12) 15 (13%) 9 (13%) 4 24 (6.7) 6 (5.7) 18 (7.1) 8 (7.0%) 5 (6.9%) pN 0.19 0.26 0 176 (49) 53 (50) 123 (48) 57 (50%) 31 (43%) 1 108 (30) 37 (35) 71 (28) 34 (30%) 30 (42%) 2 48 (13) 12 (11) 36 (14) 13 (11%) 8 (11%) 3 28 (7.8) 4 (3.8) 24 (9.4) 11 (9.6%) 3 (4.2%) Surgery 0.84 0.95 Conservative 133 (37) 40 (38) 93 (37) 41 (36%) 26 (36%) Mastectomy 227 (63) 66 (62) 161 (63) 74 (64%) 46 (64%) Radiotherapy 248 (69) 171 (67) 77 (73) 0.32 81 (70%) 53 (74%) 0.64 Anthracyclines 252 (70) 52 (49) 200 (79) < 0.01 79 (69%) 45 (63%) 0.38 Carboplatin 111 (31) 64 (60) 47 (19) < 0.01 39 (34%) 31 (43%) 0.21 Abbreviations: TNBC, triple negative breast cancer; AdjCape, adjuvant capecitabine; P, p-value; IQR, interquartile range; FH, family history; BMI, body mass index; cT, clinical T category; cN, clinical N category; HG, histological grade; LVI, lymphovascular invasion; pT, pathological T category; pN, pathological N category. Clinical Outcomes In the unmatched cohort, the median follow-up was 36.9 months (IQR 19.6–66.2). All-cause mortality was 48%, and recurrence occurred in 33% of patients. Median overall survival (OS) was 59.6 months (95% CI 49.8–75.1), and median disease-free survival (DFS) was 48.8 months (95% CI 38.1–62.6). OS at 1, 3, and 5 years was 94.8%, 66.5%, and 49.6%, respectively, while DFS at those timepoints was 86.7%, 56.8%, and 44.9%. Propensity Score Matched Analysis To address imbalances in key baseline variables, 1:2 propensity score matching (PSM) was performed, yielding a matched cohort of 187 patients: 72 in the AdjCape group and 115 in the control group. Matching achieved adequate balance across all covariates (Table 1 ). In the matched cohort, bivariate analysis showed no significant survival advantage with AdjCape. Median OS was 82.4 months in the AdjCape group vs. 52.1 months in controls (HR 0.84, 95% CI 0.54–1.30, p = 0.434), and median DFS was 62.6 vs. 32.2 months (HR 0.84, 95% CI 0.55–1.27, p = 0.407). OS rates at 1, 3, and 5 years were 100%, 67.9%, and 55.4% with AdjCape vs. 93.4%, 60.0%, and 47.0% in controls. DFS rates were 89.7%, 62.5%, and 50.1% with AdjCape vs. 83.6%, 46.4%, and 40.3% in controls. In multivariate Cox regression (Table 2 ), AdjCape remained non-significant for both OS (HR 0.79, 95% CI 0.51–1.23, p = 0.302) and DFS (HR 0.81, 95% CI 0.53–1.23, p = 0.321). Advanced residual tumor stage (pT3–pT4) was independently associated with worse OS (HR 3.14, 95% CI 1.81–5.44, p < 0.001) and DFS (HR 1.96, 95% CI 1.22–3.15, p = 0.005). HER2 low status showed a non-significant trend toward improved OS (HR 0.58, 95% CI 0.33–1.04, p = 0.068). Lack of RT was associated with worse DFS (HR 1.72, 95% CI 1.13–2.62, p = 0.012) (Fig. 2 ). Table 2 Multivariate Analysis in the Propensity Score-Matched Cohort Overall Survival (OS) VARIABLE Crude HR 95% CI, p-value Adjusted HR 95% CI, p-value Capecitabine Yes vs No 0.84 0.54–1.30, 0.434 0.79 0.51–1.23, 0.302 Her2 Low vs Null 0.58 0.33–1.03, 0.062 0.58 0.33–1.04, 0.068 LVI Yes vs No 1.64 1.01–2.65, 0.044 1.03 0.60–1.77, 0.921 pT 3–4 vs pT1-2 3.04 1.88–4.92, p < 0.001 3.14 1.81–5.44, p < 0.001 Disease-Free Survival (DFS) VARIABLE Crude HR 95% CI, p-value Adjusted HR 95% CI, p-value Capecitabine Yes vs No 0.84 0.55–1.27, 0.407 0.81 0.53–1.23, 0.321 HTN Yes vs No 0.62 0.39–0.97, 0.038 0.71 0.45–1.13, 0.146 Ductal Histology No vs Yes 1.79 0.99–3.22, 0.053 1.47 0.80–2.70, 0.219 pT 3–4 vs pT1-2 2.09 1.31–3.33, 0.002 1.96 1.22–3.15, 0.005 RT No vs Yes 1.88 1.25–2.84, 0.003 1.72 1.13–2.62, 0.012 Abbreviations: CI, confidence interval; HR, hazard ratio; LVI, Lymphovascular invasion; Her2 low was considered + 1 or + 2, and Her2 Null (0); pT, residual pathological tumor size; RT, radiotherapy; HTN, arterial hypertension. The residual pathological nodal involvement (pN) was considered in the model as a stratification variable. Stratified Analysis: High-Risk Subgroups Given the potential benefit in selected patients, a stratified analysis was conducted based on variables identified in multivariate models. AdjCape significantly improved OS and DFS in patients with high residual tumor burden (pT3–pT4): OS HR 0.29 (95% CI 0.12–0.82, p = 0.020), DFS HR 0.37 (95% CI 0.14–0.97, p = 0.044). In patients who did not receive RT, AdjCape improved DFS (HR 0.47, 95% CI 0.23–0.96, p = 0.038) and showed a non-significant trend toward better OS (HR 0.49, 95% CI 0.22–1.08, p = 0.077) (Fig. 3 ). No effect modification was observed based on HER2 status. DISCUSSION In non-metastatic TNBC, achieving pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) remains a critical prognostic milestone. Despite advances in systemic therapy, including the addition of immunotherapy, one-third of patients fail to reach pCR in even the most favorable clinical trial settings [ 15 – 17 ]. In real-world cohorts without access to immunotherapy or platinum agents, non-pCR rates remain high—up to 70% [ 18 , 19 ]. This subgroup has limited therapeutic options and a poor prognosis. In settings where pembrolizumab or olaparib is accessible, these agents offer validated improvements in overall survival (OS) and disease-free survival (DFS) for high-risk patients, including those with germline BRCA1/2 mutations [ 20 , 21 ]. Since 2017, the CREATE-X trial demonstrated a survival benefit from adjuvant capecitabine (AdjCape) in patients with TNBC and residual disease (non-pCR) [ 3 ]. However, the study's predominantly Asian cohort and the lack of consistent efficacy in subsequent trials have raised questions regarding the generalizability of these findings [ 3 , 7 ]. Conflicting results from real-world studies in other populations have further contributed to uncertainty surrounding the routine use of AdjCape in this setting [ 6 , 22 , 23 ]. We conducted a retrospective real-world evidence (RWE) study to assess the impact of AdjCape in a TNBC non-pCR population. In our cohort, 65% of patients did not achieve pCR. Limited exposure to anthracyclines and carboplatin, along with the unavailability of immunotherapy, may explain this high rate. Furthermore, many patients presented with adverse baseline characteristics, including stage III disease, large tumors (T3–T4), nodal involvement, and high histologic grade (HG). Overall outcomes were poor, with a mortality rate approaching 50% and recurrence in one-third of patients. A substantial proportion had high tumor burden at diagnosis—20% with residual pT3–pT4 or pN2–pN3—did not receive radiotherapy (31%) and had suboptimal systemic therapy. These factors likely contributed to the unfavorable prognosis. At three years, survival outcomes in our study (OS 66.5% vs. 67.9%; DFS 46.4% vs. 62.5% for control vs. AdjCape) were markedly lower than those reported in Asian cohorts, where 3-year OS exceeded 88% and DFS surpassed 73% [ 3 , 8 ]. These differences may reflect not only tumor biology but also ethnic, demographic, and systemic treatment disparities [ 3 , 24 , 25 ]. AdjCape was used in approximately one-third of our patients, mainly during the past seven years. Compared to earlier years, this period saw increased use of carboplatin and anthracycline-free regimens. The AdjCape group had a higher proportion of patients under 35, with more high-grade and T4 tumors. Although such differences may have introduced bias, our propensity score matching (PSM) achieved full covariate balance, minimizing confounding. In the matched cohort, AdjCape was not associated with improved OS or DFS in either bivariate or multivariate analysis. However, stratified analysis showed benefit in subgroups with high residual tumor burden and those who did not receive radiotherapy, consistent with findings from other observational studies [ 23 – 25 ](22–24). We found no effect in the HER2 low subgroup, mirroring previous results from Chinese populations [ 24 ]. Of note, 36.78% of patients in the AdjCape group discontinued treatment before completing six cycles, mainly due to intolerance. This discontinuation rate is higher than the 18–25% reported in CREATE-X, despite using the same starting dose of 1000 mg/m 2 twice daily. This finding is consistent with other studies indicating reduced capecitabine tolerability in non-Asian populations [ 6 , 22 , 26 ], among whom inactivating variants of the DPYD gene—encoding dihydropyrimidine dehydrogenase, the key enzyme responsible for 5-FU detoxification—are more prevalent compared to East Asians, who therefore tolerate higher doses and may achieve greater drug exposure [ 27 ]. This study has several strengths. It includes one of the largest TNBC non-pCR cohorts evaluated in a real-world setting, with detailed clinical, tumor, and treatment variables. We used rigorous PSM to reduce bias and performed stratified analyses to identify subpopulations that might benefit from AdjCape. Importantly, our findings contrast with Asian trial results, underscoring the need for population-specific data. Nonetheless, this study has several limitations. Its retrospective design introduces the possibility of residual confounding from unmeasured variables such as Ki-67, residual cancer burden, tumor-infiltrating lymphocytes, germline BRCA1/2 status, functional status, and comorbidities. The single-center setting, limited exposure to carboplatin, inclusion of some anthracycline-free regimens, and the absence of immunotherapy restrict the generalizability of the findings to current standard-of-care settings. Although the median follow-up of 36.9 months may appear short, most TNBC-related deaths occur within this time frame [ 28 ]. Despite representing one of the largest real-world cohorts of TNBC patients with residual disease evaluating adjuvant capecitabine, the study remains underpowered to assess treatment effects across all clinically relevant subgroups. Finally, the lack of data on breast cancer-specific mortality and post-recurrence treatments may confound the interpretation of overall survival outcomes. Although AdjCape remains part of the standard adjuvant approach for TNBC with non-pCR, the supporting evidence is largely based on studies conducted in Asian populations and prior to the routine use of carboplatin or immunotherapy [ 3 , 24 , 25 ]. Its role in patients with gBRCA1/2 mutations is uncertain, especially considering its limited efficacy in basal-type TNBC and the proven benefit of olaparib in this subgroup [ 7 – 9 ]. Our data suggest that AdjCape offers minimal benefit in patients with low residual burden or those who received RT—scenarios where adjuvant immunotherapy may suffice [ 2 , 15 ]. Future studies should investigate the potential synergy between capecitabine and immunotherapy, particularly in patients with high residual disease who did not receive radiotherapy. Continued generation of real-world evidence (RWE) will be essential to refine treatment strategies for this high-risk subgroup. Additionally, further RWE studies are warranted to assess the role of adjuvant capecitabine in patients with low residual tumor burden (pT1/pT2 N0), where our data showed no survival benefit. CONCLUSION In this real-world cohort of patients with TNBC and residual disease after neoadjuvant chemotherapy, adjuvant capecitabine did not improve overall or disease-free survival in the general population. However, potential benefit was observed in patients with high residual tumor burden and those who did not receive radiotherapy. These findings underscore the need for a more individualized approach to adjuvant therapy in TNBC non-pCR, and support further research to define the role of capecitabine in the context of evolving treatment paradigms, including immunotherapy and targeted agents. Declarations COMPETING INTERESTS The authors have no relevant financial or non-financial interests to disclose. FUNDING The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Author Contribution The study was conceived and designed by NG, LL and CAR. Data were collected by KM and analyzed by NG, LL and CAR. JC contributed to the results presentation and discussion. The first draft was written by NG. All authors critically read previous versions of the paper and approved the final manuscript prepared by NG and CAR. 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Management of patients with early-stage triple-negative breast cancer following pembrolizumab-based neoadjuvant therapy: What are the evidences? Cancer Treat Rev. 2022;110:102459. Liu M, Qi Y, Wang W, Sun X. Toward a better understanding about real-world evidence. Eur J Hosp Pharm. 2022;29:8–11. von Minckwitz G, Untch M, Blohmer J-U, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804. Gown AM. Current issues in ER and HER2 testing by IHC in breast cancer. Mod Pathol. 2008;21 Suppl 2:S8–15. Tolaney SM, Garrett-Mayer E, White J, Blinder VS, Foster JC, Amiri-Kordestani L, et al. Updated Standardized Definitions for Efficacy End Points (STEEP) in Adjuvant Breast Cancer Clinical Trials: STEEP Version 2.0. J Clin Oncol. 2021;39:2720–31. Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020;382:810–21. Gianni L, Huang CS, Egle D, Bermejo B, Zamagni C, Thill M, et al. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study. Ann Oncol. 2022;33:534–43. Loibl S, Schneeweiss A, Huober J, Braun M, Rey J, Blohmer J-U, et al. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann Oncol. 2022;33:1149–58. Lara-Medina F, Pérez-Sánchez V, Saavedra-Pérez D, Blake-Cerda M, Arce C, Motola-Kuba D, et al. Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis, and association with menopausal status, body mass index, and parity. Cancer. 2011;117:3658–69. Acevedo F, Walbaum B, Medina L, Merino T, Camus M, Puschel K, et al. Clinical characteristics, risk factors, and outcomes in Chilean triple negative breast cancer patients: a real-world study. Breast Cancer Res Treat. 2023;197:449–59. Loibl S, André F, Bachelot T, Barrios CH, Bergh J, Burstein HJ, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35:159–82. National Comprehensive Cancer Network. Breast Cancer Guidelines [Internet]. NCCN. [cited 2025 May 20]. Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419 Pereira MFI, Buzatto IPC, Carrara HHA, Buono F de O, de Andrade JM, Orlandini LF, et al. Real-world data on adjuvant capecitabine after standard neoadjuvant chemotherapy for triple negative breast cancer. Rev Bras Ginecol Obstet. 2024;46:e-rbgo29. Dülgar Ö, Öven BB, Atcı MM, Arıkan R, Ay S, Ayhan M, et al. Is the benefit of using adjuvant capecitabine in patients with residual triple-negative breast cancer related to pathological response to neoadjuvant chemotherapy? Expert Rev Anticancer Ther. 2022;22:773–80. Ma Y, Zhu M, Zhang J, Jiao D, Hou Y, Chen X, et al. Efficacy of adjuvant capecitabine in triple-negative breast cancer with residual disease after neoadjuvant therapy: a real-world study. Breast. 2025;81:104477. Kim MJ, Kim HJ, Kim J-Y, Shin J, Park YH. Effectiveness of Adjuvant Capecitabine in Triple-Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Treatment: A Real-World Evidence Study in Korea. Clin Breast Cancer. 2025;S1526-8209(24)00369-0. Sullivan M, Lei X, Karuturi M, Malinowski C, Giordano SH, Chavez-MacGregor M. Use of adjuvant capecitabine in older patients with early-stage triple-negative breast cancer. Breast Cancer Res Treat. 2025;211:213–21. White C, Scott RJ, Paul C, Ziolkowski A, Mossman D, Ackland S. Ethnic Diversity of DPD Activity and the DPYD Gene: Review of the Literature. Pharmgenomics Pers Med. 2021;14:1603–17. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429–34. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 16 Sep, 2025 Read the published version in Breast Cancer Research and Treatment → Version 1 posted Editorial decision: Revision requested 24 Jul, 2025 Reviews received at journal 24 Jul, 2025 Reviews received at journal 16 Jul, 2025 Reviewers agreed at journal 15 Jul, 2025 Reviewers agreed at journal 10 Jul, 2025 Reviews received at journal 09 Jul, 2025 Reviewers agreed at journal 09 Jul, 2025 Reviewers invited by journal 09 Jul, 2025 Editor assigned by journal 23 Jun, 2025 Submission checks completed at journal 23 Jun, 2025 First submitted to journal 22 Jun, 2025 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. 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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-6951831","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":484306215,"identity":"00c16154-9e1e-4b4d-9af7-6dc311c13008","order_by":0,"name":"Noiver Graciano","email":"","orcid":"","institution":"Universidad Pontificia Bolivariana","correspondingAuthor":false,"prefix":"","firstName":"Noiver","middleName":"","lastName":"Graciano","suffix":""},{"id":484306216,"identity":"3d088a55-624d-4f10-ae73-678c28f85b72","order_by":1,"name":"Lucelly López","email":"","orcid":"","institution":"Universidad Pontificia Bolivariana","correspondingAuthor":false,"prefix":"","firstName":"Lucelly","middleName":"","lastName":"López","suffix":""},{"id":484306217,"identity":"d7c96669-7b66-4996-b3ca-a061fd609b0f","order_by":2,"name":"Carlos A. Rodriguez","email":"data:image/png;base64,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","orcid":"","institution":"Universidad de Antioquia","correspondingAuthor":true,"prefix":"","firstName":"Carlos","middleName":"A.","lastName":"Rodriguez","suffix":""},{"id":484306218,"identity":"7fbd74bf-972b-4e53-8ec0-8933dfd40c33","order_by":3,"name":"Katherine Montoya","email":"","orcid":"","institution":"Fundación AUNA-IDEAS","correspondingAuthor":false,"prefix":"","firstName":"Katherine","middleName":"","lastName":"Montoya","suffix":""},{"id":484306219,"identity":"81c24a95-388d-4450-a1f6-d58aa503a914","order_by":4,"name":"Javier Cortés","email":"","orcid":"","institution":"International Breast Cancer Center (IBCC), Quiron Group","correspondingAuthor":false,"prefix":"","firstName":"Javier","middleName":"","lastName":"Cortés","suffix":""}],"badges":[],"createdAt":"2025-06-23 01:38:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6951831/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6951831/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10549-025-07814-3","type":"published","date":"2025-09-16T15:57:37+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86673290,"identity":"0d19ac62-502f-437a-8165-fbbcb75df4f9","added_by":"auto","created_at":"2025-07-14 11:46:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":18651,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of patient selection from 2008 to 2024 showing the timing of chemotherapy (neoadjuvant NACT vs adjuvant ACT), the pathological complete response (pCR) in the NACT group and the use of adjuvant capecitabine.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6951831/v1/cc5d019e67f3f311dafd4a7c.png"},{"id":86673293,"identity":"7e7d3a5e-7292-4fa4-a87b-e001d210b221","added_by":"auto","created_at":"2025-07-14 11:46:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":844707,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival and disease-free survival in the propensity score matched cohort. Panels A and B show the effect of adjuvant capecitabine vs observation; panels C and D display the effect of HER2 low vs HER2 null status; panels E and F illustrate the effect of residual tumor load (pT1-pT2 vs pT3-pT4).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6951831/v1/598087f154d5e80d2edf7a5f.png"},{"id":86673294,"identity":"f55787ef-7324-4f44-ae27-19956c664090","added_by":"auto","created_at":"2025-07-14 11:46:00","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":976957,"visible":true,"origin":"","legend":"\u003cp\u003eStratified analysis in the propensity score matched cohort of capecitabine efficacy based on residual tumor load and radiotherapy use. Panels A–D present the analysis based on residual tumor size (pT1–pT2 or pT3–T4), panels A and B correspond to overall survival (OS), and panels C and D to disease-free survival (DFS). Panels E–H present the analysis based on radiotherapy (RT) use, panels E and F correspond to OS, and Panels G and H to DFS.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6951831/v1/076a30e4e06a70e8c66ef87f.png"},{"id":91889874,"identity":"3f853645-9318-41b2-98be-a77bff4c0007","added_by":"auto","created_at":"2025-09-22 16:03:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2902939,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6951831/v1/6f801264-a444-4f42-97c3-6199f63c048e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Survival Impact of Adjuvant Capecitabine In Triple-Negative Breast Cancer Patients with Residual Disease: A Real-World Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eTriple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, with the poorest prognosis among women with operable disease [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The subgroup of patients who fail to achieve pathological complete response (non-pCR) after neoadjuvant chemotherapy (NACT) accounts for the majority of breast cancer-related deaths in this population [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], and therapeutic options to improve outcomes remain limited.\u003c/p\u003e\u003cp\u003eThe CREATE-X trial demonstrated that adjuvant capecitabine (AdjCape) significantly improved 5-year overall survival (OS) and disease-free survival (DFS) in Asian patients with non-pCR, with absolute benefits of 5.6% and 6.5%, respectively [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, differences in baseline prognosis, drug metabolism, and treatment tolerance between Asian and non-Asian populations have raised questions about the generalizability of these findings [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRecent integration of platinum-based agents and immunotherapy (e.g., pembrolizumab) into NACT regimens\u0026mdash;therapies not included in earlier AdjCape studies\u0026mdash;has altered the landscape of residual disease, potentially modifying both the biological profile and treatment responsiveness. Moreover, the efficacy of capecitabine in specific molecular subtypes, such as basal-like tumors or BRCA1/2 mutation carriers, remains uncertain, particularly as olaparib has shown superior outcomes in these settings [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the absence of clear guidelines for post-NACT management in TNBC non-pCR, questions remain regarding the optimal sequencing, combination, or de-escalation of adjuvant therapies [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Evaluating the efficacy of AdjCape in broader populations and identifying patients most likely to benefit is therefore essential.\u003c/p\u003e\u003cp\u003eReal-world evidence (RWE) provides critical insights where randomized controlled trials are limited or unfeasible, enabling the assessment of treatment effects, toxicity profiles, and external validity in heterogeneous clinical contexts [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This study aimed to evaluate the impact of AdjCape on OS and DFS in a real-world cohort of non-metastatic TNBC patients with non-pCR, adjusting for potential confounders using propensity score methods.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design, Population, and Data Collection\u003c/h2\u003e\u003cp\u003eThis retrospective cohort study was conducted at the Instituto de Cancerolog\u0026iacute;a, Cl\u0026iacute;nica Las Am\u0026eacute;ricas\u0026ndash;AUNA (IDCLA-AUNA) in Medell\u0026iacute;n, Colombia, and included all women diagnosed with de novo non-metastatic triple-negative breast cancer (TNBC) between January 1, 2008, and December 31, 2024. Eligible patients received at least one cycle of neoadjuvant chemotherapy (NACT), underwent definitive surgery, and had a non-complete pathological response (non-pCR) on final pathology. Pathologic complete response (pCR) was defined as the absence of residual invasive carcinoma in the breast and axillary nodes, allowing for residual ductal carcinoma in situ (ypT0/is/ypN0) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTNBC status was confirmed by institutional pathologists and defined by the absence of estrogen receptors (positivity\u0026thinsp;\u0026lt;\u0026thinsp;1%) and HER2 negativity (IHC score of 0 or 1+, or 2\u0026thinsp;+\u0026thinsp;with negative FISH). HER2 low was defined as IHC 1\u0026thinsp;+\u0026thinsp;or 2\u0026thinsp;+\u0026thinsp;with negative FISH; HER2 null was IHC 0.\u003c/p\u003e\u003cp\u003ePatients were excluded if they had incomplete clinical or histopathological data, a history of synchronous or metachronous breast cancer, other malignancies (except basal or squamous cell skin cancers), or had not provided informed consent for research use of their medical records.\u003c/p\u003e\u003cp\u003eCollected demographic and clinical data included: age, health insurance type (contributory or subsidized), comorbidities (diabetes, hypertension), parity, menopausal status, family history of breast cancer, and body mass index (BMI). Tumor-related variables included imaging modality at diagnosis, histological subtype, histological grade (HG), HER2 low status, and presence of lymphovascular invasion (LVI). HG was classified using Scarff-Bloom-Richardson criteria; histology and LVI were categorized per WHO and CAP guidelines [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Staging followed the 8th edition of the AJCC classification.\u003c/p\u003e\u003cp\u003eSurgical approach (mastectomy vs. breast-conserving surgery) was determined by the treating surgeon, with preference for conserving surgery when negative margins were achievable. NACT regimens primarily consisted of anthracyclines, cyclophosphamide, and taxanes; carboplatin was introduced from 2017. For patients ineligible for anthracyclines, CMF (cyclophosphamide, methotrexate, 5-fluorouracil) or taxane-based regimens were used. Chemotherapy continued for up to six months or until dose-limiting toxicity occurred. Pembrolizumab and olaparib were not available during the study period.\u003c/p\u003e\u003cp\u003eRadiotherapy (RT) was prescribed based on standard indications, including breast-conserving surgery, positive margins, nodal involvement, or tumor size\u0026thinsp;\u0026gt;\u0026thinsp;5 cm in mastectomy cases. Multidisciplinary tumor boards evaluated cases with treatment ambiguity.\u003c/p\u003e\u003cp\u003eData were extracted from the institutional REDCap-based Breast Cancer Module, which includes prospectively recorded clinical records. Any inconsistencies were verified against original medical records. The study was approved by the Institutional Ethics Committee (Act 220\u0026ndash;2024) and conducted in accordance with the Declaration of Helsinki and Colombian Ministry of Health resolution 8430 of 1993.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eExposures and Outcomes\u003c/h3\u003e\n\u003cp\u003eThe primary exposure was the use of adjuvant capecitabine (AdjCape), administered following surgery or after completion of RT when indicated. The treatment regimen consisted of 1000 mg/m\u003csup\u003e2\u003c/sup\u003e bid orally on days 1\u0026ndash;14 of a 21-day cycle for 6\u0026ndash;8 cycles. Dose adjustments were made for toxicity.\u003c/p\u003e\u003cp\u003eThe primary endpoint was overall survival (OS), defined as time from curative-intent surgery to death from any cause or last contact. The secondary endpoint was disease-free survival (DFS), defined as time from surgery to recurrence (local or distant), contralateral breast cancer, death, or last contact. Outcomes were defined using the STEEP version 2.0 criteria [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], with mortality verified through Colombia\u0026rsquo;s national civil registry as of March 15, 2025.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eData Analysis\u003c/h2\u003e\u003cp\u003eDescriptive statistics were used to characterize the cohort. Continuous variables were summarized using mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median with interquartile range (IQR), based on the Shapiro-Wilk test for normality. Categorical variables were reported as frequencies and percentages.\u003c/p\u003e\u003cp\u003eTo reduce treatment selection bias, 2:1 propensity score matching (PSM) was applied using a nearest neighbor method with a caliper of 0.1. Matching was based on pre-treatment variables: age, health insurance, family history, clinical stage, BMI, histological grade, LVI, HER2 low status, surgery type, and use of anthracyclines, carboplatin, and RT.\u003c/p\u003e\u003cp\u003eSurvival analysis was conducted using Kaplan\u0026ndash;Meier estimates and log-rank tests. Cox proportional hazards models were constructed for variables with p\u0026thinsp;\u0026le;\u0026thinsp;0.1 in univariate analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and the proportional hazards assumption was verified.\u003c/p\u003e\u003cp\u003ePre-specified subgroup analyses were performed for HER2 status (low vs. null), pathological tumor size (pT1\u0026ndash;pT2 vs. pT3\u0026ndash;pT4), and RT use to explore heterogeneity in treatment effect.\u003c/p\u003e\u003cp\u003eAll analyses were conducted using R version 4.4.2 and Jamovi version 2.6.44, with the MatchIt, Matching, cobalt, psych, survival, and survminer packages.\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eClinical and Tumor Characteristics at Diagnosis and Treatment\u003c/h2\u003e\u003cp\u003eBetween 2008 and 2024, 744 patients with non-metastatic triple-negative breast cancer (TNBC) were identified at the study center. Among them, 556 (74.7%) received neoadjuvant chemotherapy (NACT), and 360 (65%) exhibited residual invasive disease (non-pCR) and met the eligibility criteria. Of these, 106 patients (29.4%) received adjuvant capecitabine (AdjCape) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn the overall cohort, the most frequent age group was 51\u0026ndash;70 years (47%). Most patients were postmenopausal (64%) and had children (82%), with a high prevalence of overweight (41%) and obesity (23%).\u003c/p\u003e\u003cp\u003eApproximately half of the cohort presented with stage III disease at diagnosis. Advanced primary tumor size (T3\u0026ndash;T4) and nodal involvement were present in 51% and 61% of cases, respectively. Histologically, 90% of tumors were ductal, 76% had high histologic grade (HG), and 20% showed lymphovascular invasion (LVI). HER2 low expression, high residual tumor burden (pT3\u0026ndash;pT4), and high nodal stage (pN2\u0026ndash;pN3) were each observed in about 20% of patients.\u003c/p\u003e\u003cp\u003eRegarding treatment, 63% underwent mastectomy, 69% received radiotherapy (RT), and 70% were treated with anthracyclines. Carboplatin was used in 31% of cases. Among patients receiving AdjCape, 36.8% completed fewer than six cycles, primarily due to intolerance; progression accounted for seven discontinuations.\u003c/p\u003e\u003cp\u003eCompared to controls, the AdjCape group included a higher proportion of patients aged\u0026thinsp;\u0026lt;\u0026thinsp;35 years (19% vs. 10%), with a family history of breast cancer (48% vs. 28%) and low-grade tumors (HG 1\u0026ndash;2: 31.6% vs. 21.5%). In contrast, the control group had more patients with T4 tumors (28% vs. 18%) and HER2 low status (30% vs. 15%). No significant differences were found in clinical stage or residual tumor burden. The control group had higher anthracycline use (79% vs. 49%) and lower carboplatin use (19% vs. 60%). RT and surgical approach were balanced between groups (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\u003e Characteristics of Patients with TNBC According to Capecitabine Use and Matching with Propensity Score\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVARIABLE\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003eN(%)\u0026thinsp;=\u0026thinsp;360\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAdjCape\u003c/p\u003e\u003cp\u003eN(%)\u0026thinsp;=\u0026thinsp;106\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo AdjCape\u003c/p\u003e\u003cp\u003eN(%)\u0026thinsp;=\u0026thinsp;254\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAdjCape\u003c/p\u003e\u003cp\u003eN(%)\u0026thinsp;=\u0026thinsp;72\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNo AdjCape\u003c/p\u003e\u003cp\u003eN(%)\u0026thinsp;=\u0026thinsp;115\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eUnmatched cohort\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u003cp\u003ePS-matched cohort\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge in years (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53 (44, 63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (42, 61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e54 (45, 63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e54 (45, 63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e53 (43, 62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCategorized age (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12 (17%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e35\u0026ndash;50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e114 (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e81 (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39 (34%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e24 (33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e51\u0026ndash;70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e168 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42 (40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e126 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e54 (47%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e31 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (8.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21 (8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5 (6.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHealth insurance\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eContributory\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e309 (86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100 (94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e209 (82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e103 (90%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e67 (93%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSubsidized\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51 (14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e45 (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12 (10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5 (6.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFH of breast cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e123 (34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51 (48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e72 (28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e42 (37%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e29 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMenopause\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e230 (64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65 (61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e165 (65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e40 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e26 (36%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33 (9.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6 (8.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.90\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e128 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100 (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39 (34%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e21 (29%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChildren\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e294 (82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e45 (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e14 (19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.93\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e130 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34 (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e96 (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e43 (37%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e25 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverweight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e149 (41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e99 (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e46 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e31 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObese\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e81 (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e59 (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e26 (23%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e16 (22%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMammography\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e248 (69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e76 (72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e172 (68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e78 (68%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e54 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUltrasound/MRI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e112 (31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e82 (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e37 (32%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumoral stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (4.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (6.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (3.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5 (4.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4 (5.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e169 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e117 (46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e57 (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e34 (47%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47 (44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e129 (51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e53 (46%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e34 (47%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.06\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.83\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27 (7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7 (9.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e151 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43 (41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e108 (43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e50 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e31 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e92 (26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60 (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e28 (24%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e20 (28%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e90 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e71 (28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e28 (24%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e14 (19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.56\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e141 (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e91 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e44 (38%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e34 (47%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e138 (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e105 (41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e45 (39%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e22 (31%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e69 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e15 (21%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (1.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (3.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (2.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (1.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuctal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e324 (90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93 (88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e231 (91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e103 (90%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e65 (90%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo ductal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23 (9.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12 (10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7 (9.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.08\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (3.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4 (3.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3 (4.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e75 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e45 (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e25 (22%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e273 (76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e73 (69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e200 (79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e86 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e51 (71%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e51 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e28 (24%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e16 (22%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHER2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e291 (81%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e217 (85%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74 (70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e92 (80%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e54 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e69 (19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (15%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e32 (30%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (6.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (6.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (5.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5 (6.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e174 (48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e122 (48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e56 (49%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e33 (46%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e92 (26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24 (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e68 (27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e30 (26%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e20 (28%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30 (12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15 (13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9 (13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (7.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8 (7.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5 (6.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.26\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e176 (49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e123 (48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e57 (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e31 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e108 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e71 (28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e34 (30%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e30 (42%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36 (14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (7.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 (9.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 (9.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3 (4.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConservative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e133 (37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40 (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e93 (37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e41 (36%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e26 (36%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMastectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e227 (63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66 (62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e161 (63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e74 (64%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e46 (64%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadiotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e248 (69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e171 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e77 (73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e81 (70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e53 (74%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnthracyclines\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e252 (70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e200 (79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e79 (69%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e45 (63%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCarboplatin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e111 (31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64 (60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e47 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39 (34%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e31 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003eAbbreviations: TNBC, triple negative breast cancer; AdjCape, adjuvant capecitabine; P, p-value; IQR, interquartile range; FH, family history; BMI, body mass index; cT, clinical T category; cN, clinical N category; HG, histological grade; LVI, lymphovascular invasion; pT, pathological T category; pN, pathological N category.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eClinical Outcomes\u003c/h2\u003e\u003cp\u003eIn the unmatched cohort, the median follow-up was 36.9 months (IQR 19.6\u0026ndash;66.2). All-cause mortality was 48%, and recurrence occurred in 33% of patients. Median overall survival (OS) was 59.6 months (95% CI 49.8\u0026ndash;75.1), and median disease-free survival (DFS) was 48.8 months (95% CI 38.1\u0026ndash;62.6). OS at 1, 3, and 5 years was 94.8%, 66.5%, and 49.6%, respectively, while DFS at those timepoints was 86.7%, 56.8%, and 44.9%.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePropensity Score Matched Analysis\u003c/h3\u003e\n\u003cp\u003eTo address imbalances in key baseline variables, 1:2 propensity score matching (PSM) was performed, yielding a matched cohort of 187 patients: 72 in the AdjCape group and 115 in the control group. Matching achieved adequate balance across all covariates (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn the matched cohort, bivariate analysis showed no significant survival advantage with AdjCape. Median OS was 82.4 months in the AdjCape group vs. 52.1 months in controls (HR 0.84, 95% CI 0.54\u0026ndash;1.30, p\u0026thinsp;=\u0026thinsp;0.434), and median DFS was 62.6 vs. 32.2 months (HR 0.84, 95% CI 0.55\u0026ndash;1.27, p\u0026thinsp;=\u0026thinsp;0.407). OS rates at 1, 3, and 5 years were 100%, 67.9%, and 55.4% with AdjCape vs. 93.4%, 60.0%, and 47.0% in controls. DFS rates were 89.7%, 62.5%, and 50.1% with AdjCape vs. 83.6%, 46.4%, and 40.3% in controls.\u003c/p\u003e\u003cp\u003eIn multivariate Cox regression (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), AdjCape remained non-significant for both OS (HR 0.79, 95% CI 0.51\u0026ndash;1.23, p\u0026thinsp;=\u0026thinsp;0.302) and DFS (HR 0.81, 95% CI 0.53\u0026ndash;1.23, p\u0026thinsp;=\u0026thinsp;0.321). Advanced residual tumor stage (pT3\u0026ndash;pT4) was independently associated with worse OS (HR 3.14, 95% CI 1.81\u0026ndash;5.44, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and DFS (HR 1.96, 95% CI 1.22\u0026ndash;3.15, p\u0026thinsp;=\u0026thinsp;0.005). HER2 low status showed a non-significant trend toward improved OS (HR 0.58, 95% CI 0.33\u0026ndash;1.04, p\u0026thinsp;=\u0026thinsp;0.068). Lack of RT was associated with worse DFS (HR 1.72, 95% CI 1.13\u0026ndash;2.62, p\u0026thinsp;=\u0026thinsp;0.012) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" 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\u003eMultivariate Analysis in the Propensity Score-Matched Cohort\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\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eOverall Survival (OS)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVARIABLE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eCrude HR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e95% CI, p-value\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eAdjusted HR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e95% CI, p-value\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCapecitabine Yes vs No\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.54\u0026ndash;1.30, 0.434\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.51\u0026ndash;1.23, 0.302\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHer2 Low vs Null\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.58\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.33\u0026ndash;1.03, 0.062\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.58\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.33\u0026ndash;1.04, 0.068\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVI Yes vs No\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.01\u0026ndash;2.65, 0.044\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.60\u0026ndash;1.77, 0.921\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT 3\u0026ndash;4 vs pT1-2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e3.04\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e1.88\u0026ndash;4.92, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e3.14\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e1.81\u0026ndash;5.44, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eDisease-Free Survival (DFS)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVARIABLE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eCrude HR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e95% CI, p-value\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eAdjusted HR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e95% CI, p-value\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCapecitabine Yes vs No\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.55\u0026ndash;1.27, 0.407\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.53\u0026ndash;1.23, 0.321\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHTN Yes vs No\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.39\u0026ndash;0.97, 0.038\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.45\u0026ndash;1.13, 0.146\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuctal Histology No vs Yes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.99\u0026ndash;3.22, 0.053\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.80\u0026ndash;2.70, 0.219\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT 3\u0026ndash;4 vs pT1-2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e2.09\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e1.31\u0026ndash;3.33, 0.002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e1.96\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e1.22\u0026ndash;3.15, 0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRT No vs Yes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e1.88\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e1.25\u0026ndash;2.84, 0.003\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e1.72\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e1.13\u0026ndash;2.62, 0.012\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eAbbreviations: CI, confidence interval; HR, hazard ratio; LVI, Lymphovascular invasion; Her2 low was considered\u0026thinsp;+\u0026thinsp;1 or +\u0026thinsp;2, and Her2 Null (0); pT, residual pathological tumor size; RT, radiotherapy; HTN, arterial hypertension. The residual pathological nodal involvement (pN) was considered in the model as a stratification variable.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eStratified Analysis: High-Risk Subgroups\u003c/h3\u003e\n\u003cp\u003eGiven the potential benefit in selected patients, a stratified analysis was conducted based on variables identified in multivariate models. AdjCape significantly improved OS and DFS in patients with high residual tumor burden (pT3\u0026ndash;pT4): OS HR 0.29 (95% CI 0.12\u0026ndash;0.82, p\u0026thinsp;=\u0026thinsp;0.020), DFS HR 0.37 (95% CI 0.14\u0026ndash;0.97, p\u0026thinsp;=\u0026thinsp;0.044). In patients who did not receive RT, AdjCape improved DFS (HR 0.47, 95% CI 0.23\u0026ndash;0.96, p\u0026thinsp;=\u0026thinsp;0.038) and showed a non-significant trend toward better OS (HR 0.49, 95% CI 0.22\u0026ndash;1.08, p\u0026thinsp;=\u0026thinsp;0.077) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). No effect modification was observed based on HER2 status.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn non-metastatic TNBC, achieving pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) remains a critical prognostic milestone. Despite advances in systemic therapy, including the addition of immunotherapy, one-third of patients fail to reach pCR in even the most favorable clinical trial settings [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In real-world cohorts without access to immunotherapy or platinum agents, non-pCR rates remain high\u0026mdash;up to 70% [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This subgroup has limited therapeutic options and a poor prognosis. In settings where pembrolizumab or olaparib is accessible, these agents offer validated improvements in overall survival (OS) and disease-free survival (DFS) for high-risk patients, including those with germline BRCA1/2 mutations [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSince 2017, the CREATE-X trial demonstrated a survival benefit from adjuvant capecitabine (AdjCape) in patients with TNBC and residual disease (non-pCR) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the study's predominantly Asian cohort and the lack of consistent efficacy in subsequent trials have raised questions regarding the generalizability of these findings [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Conflicting results from real-world studies in other populations have further contributed to uncertainty surrounding the routine use of AdjCape in this setting [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWe conducted a retrospective real-world evidence (RWE) study to assess the impact of AdjCape in a TNBC non-pCR population. In our cohort, 65% of patients did not achieve pCR. Limited exposure to anthracyclines and carboplatin, along with the unavailability of immunotherapy, may explain this high rate. Furthermore, many patients presented with adverse baseline characteristics, including stage III disease, large tumors (T3\u0026ndash;T4), nodal involvement, and high histologic grade (HG).\u003c/p\u003e\u003cp\u003eOverall outcomes were poor, with a mortality rate approaching 50% and recurrence in one-third of patients. A substantial proportion had high tumor burden at diagnosis\u0026mdash;20% with residual pT3\u0026ndash;pT4 or pN2\u0026ndash;pN3\u0026mdash;did not receive radiotherapy (31%) and had suboptimal systemic therapy. These factors likely contributed to the unfavorable prognosis. At three years, survival outcomes in our study (OS 66.5% vs. 67.9%; DFS 46.4% vs. 62.5% for control vs. AdjCape) were markedly lower than those reported in Asian cohorts, where 3-year OS exceeded 88% and DFS surpassed 73% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These differences may reflect not only tumor biology but also ethnic, demographic, and systemic treatment disparities [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAdjCape was used in approximately one-third of our patients, mainly during the past seven years. Compared to earlier years, this period saw increased use of carboplatin and anthracycline-free regimens. The AdjCape group had a higher proportion of patients under 35, with more high-grade and T4 tumors. Although such differences may have introduced bias, our propensity score matching (PSM) achieved full covariate balance, minimizing confounding.\u003c/p\u003e\u003cp\u003eIn the matched cohort, AdjCape was not associated with improved OS or DFS in either bivariate or multivariate analysis. However, stratified analysis showed benefit in subgroups with high residual tumor burden and those who did not receive radiotherapy, consistent with findings from other observational studies [\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e](22\u0026ndash;24). We found no effect in the HER2 low subgroup, mirroring previous results from Chinese populations [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOf note, 36.78% of patients in the AdjCape group discontinued treatment before completing six cycles, mainly due to intolerance. This discontinuation rate is higher than the 18\u0026ndash;25% reported in CREATE-X, despite using the same starting dose of 1000 mg/m\u003csup\u003e2\u003c/sup\u003e twice daily. This finding is consistent with other studies indicating reduced capecitabine tolerability in non-Asian populations [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], among whom inactivating variants of the \u003cem\u003eDPYD\u003c/em\u003e gene\u0026mdash;encoding dihydropyrimidine dehydrogenase, the key enzyme responsible for 5-FU detoxification\u0026mdash;are more prevalent compared to East Asians, who therefore tolerate higher doses and may achieve greater drug exposure [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis study has several strengths. It includes one of the largest TNBC non-pCR cohorts evaluated in a real-world setting, with detailed clinical, tumor, and treatment variables. We used rigorous PSM to reduce bias and performed stratified analyses to identify subpopulations that might benefit from AdjCape. Importantly, our findings contrast with Asian trial results, underscoring the need for population-specific data.\u003c/p\u003e\u003cp\u003eNonetheless, this study has several limitations. Its retrospective design introduces the possibility of residual confounding from unmeasured variables such as Ki-67, residual cancer burden, tumor-infiltrating lymphocytes, germline BRCA1/2 status, functional status, and comorbidities. The single-center setting, limited exposure to carboplatin, inclusion of some anthracycline-free regimens, and the absence of immunotherapy restrict the generalizability of the findings to current standard-of-care settings. Although the median follow-up of 36.9 months may appear short, most TNBC-related deaths occur within this time frame [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Despite representing one of the largest real-world cohorts of TNBC patients with residual disease evaluating adjuvant capecitabine, the study remains underpowered to assess treatment effects across all clinically relevant subgroups. Finally, the lack of data on breast cancer-specific mortality and post-recurrence treatments may confound the interpretation of overall survival outcomes.\u003c/p\u003e\u003cp\u003eAlthough AdjCape remains part of the standard adjuvant approach for TNBC with non-pCR, the supporting evidence is largely based on studies conducted in Asian populations and prior to the routine use of carboplatin or immunotherapy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Its role in patients with gBRCA1/2 mutations is uncertain, especially considering its limited efficacy in basal-type TNBC and the proven benefit of olaparib in this subgroup [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Our data suggest that AdjCape offers minimal benefit in patients with low residual burden or those who received RT\u0026mdash;scenarios where adjuvant immunotherapy may suffice [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFuture studies should investigate the potential synergy between capecitabine and immunotherapy, particularly in patients with high residual disease who did not receive radiotherapy. Continued generation of real-world evidence (RWE) will be essential to refine treatment strategies for this high-risk subgroup. Additionally, further RWE studies are warranted to assess the role of adjuvant capecitabine in patients with low residual tumor burden (pT1/pT2 N0), where our data showed no survival benefit.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn this real-world cohort of patients with TNBC and residual disease after neoadjuvant chemotherapy, adjuvant capecitabine did not improve overall or disease-free survival in the general population. However, potential benefit was observed in patients with high residual tumor burden and those who did not receive radiotherapy. These findings underscore the need for a more individualized approach to adjuvant therapy in TNBC non-pCR, and support further research to define the role of capecitabine in the context of evolving treatment paradigms, including immunotherapy and targeted agents.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eCOMPETING INTERESTS\u003c/h2\u003e\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFUNDING\u003c/h2\u003e\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eThe study was conceived and designed by NG, LL and CAR. Data were collected by KM and analyzed by NG, LL and CAR. JC contributed to the results presentation and discussion. The first draft was written by NG. All authors critically read previous versions of the paper and approved the final manuscript prepared by NG and CAR.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated or analyzed during the current study are not publicly available due to the institutional policies of Instituto de Cancerolog\u0026iacute;a Las Am\u0026eacute;ricas-AUNA, but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHwang K-T, Kim J, Jung J, Chang JH, Chai YJ, Oh SW, et al. Impact of Breast Cancer Subtypes on Prognosis of Women with Operable Invasive Breast Cancer: A Population-based Study Using SEER Database. Clin Cancer Res. 2019;25:1970\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eSchmid P, Cortes J, Dent R, McArthur H, Pusztai L, K\u0026uuml;mmel S, et al. Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer. N Engl J Med. 2024;391:1981\u0026ndash;91. \u003c/li\u003e\n\u003cli\u003eMasuda N, Lee S-J, Ohtani S, Im Y-H, Lee E-S, Yokota I, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376:2147\u0026ndash;59. \u003c/li\u003e\n\u003cli\u003eWang X, Wang S-S, Huang H, Cai L, Zhao L, Peng R-J, et al. Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial. JAMA. 2021;325:50\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eHaller DG, Cassidy J, Clarke SJ, Cunningham D, Van Cutsem E, Hoff PM, et al. Potential regional differences for the tolerability profiles of fluoropyrimidines. J Clin Oncol. 2008;26:2118\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eJones T, Beard V, Mahajan S, Jain AL, Harris LJ, Miller EM, et al. 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A Randomised, Double-blind, Parallel Group, Placebo-controlled Multi-centre Phase III Study to Assess the Efficacy and Safety of Olaparib Versus Placebo as Adjuvant Treatment in Patients With gBRCA1\u0026amp;#x2F;2 Mutations and High Risk HER2 Negative Primary Breast Cancer Who Have Completed Definitive Local Treatment and Neoadjuvant or Adjuvant Chemotherapy [Internet]. clinicaltrials.gov; 2024 Jul. Report No.: NCT02032823. Available from: https://clinicaltrials.gov/study/NCT02032823\u003c/li\u003e\n\u003cli\u003eBonadio RC, Tarantino P, Testa L, Punie K, Pernas S, Barrios C, et al. Management of patients with early-stage triple-negative breast cancer following pembrolizumab-based neoadjuvant therapy: What are the evidences? Cancer Treat Rev. 2022;110:102459. \u003c/li\u003e\n\u003cli\u003eLiu M, Qi Y, Wang W, Sun X. Toward a better understanding about real-world evidence. 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Real-world data on adjuvant capecitabine after standard neoadjuvant chemotherapy for triple negative breast cancer. Rev Bras Ginecol Obstet. 2024;46:e-rbgo29. \u003c/li\u003e\n\u003cli\u003eD\u0026uuml;lgar \u0026Ouml;, \u0026Ouml;ven BB, Atcı MM, Arıkan R, Ay S, Ayhan M, et al. Is the benefit of using adjuvant capecitabine in patients with residual triple-negative breast cancer related to pathological response to neoadjuvant chemotherapy? Expert Rev Anticancer Ther. 2022;22:773\u0026ndash;80. \u003c/li\u003e\n\u003cli\u003eMa Y, Zhu M, Zhang J, Jiao D, Hou Y, Chen X, et al. Efficacy of adjuvant capecitabine in triple-negative breast cancer with residual disease after neoadjuvant therapy: a real-world study. Breast. 2025;81:104477. \u003c/li\u003e\n\u003cli\u003eKim MJ, Kim HJ, Kim J-Y, Shin J, Park YH. Effectiveness of Adjuvant Capecitabine in Triple-Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Treatment: A Real-World Evidence Study in Korea. Clin Breast Cancer. 2025;S1526-8209(24)00369-0. \u003c/li\u003e\n\u003cli\u003eSullivan M, Lei X, Karuturi M, Malinowski C, Giordano SH, Chavez-MacGregor M. Use of adjuvant capecitabine in older patients with early-stage triple-negative breast cancer. Breast Cancer Res Treat. 2025;211:213\u0026ndash;21. \u003c/li\u003e\n\u003cli\u003eWhite C, Scott RJ, Paul C, Ziolkowski A, Mossman D, Ackland S. Ethnic Diversity of DPD Activity and the DPYD Gene: Review of the Literature. Pharmgenomics Pers Med. 2021;14:1603\u0026ndash;17. \u003c/li\u003e\n\u003cli\u003eDent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429\u0026ndash;34. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"breast-cancer-research-and-treatment","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brea","sideBox":"Learn more about [Breast Cancer Research and Treatment](https://www.springer.com/journal/10549)","snPcode":"10549","submissionUrl":"https://submission.nature.com/new-submission/10549/3","title":"Breast Cancer Research and Treatment","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"triple-negative breast cancer, adjuvant capecitabine, residual disease, survival, real-world evidence, propensity score","lastPublishedDoi":"10.21203/rs.3.rs-6951831/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6951831/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003ePatients with triple-negative breast cancer (TNBC) who do not achieve pathological complete response (non-pCR) after neoadjuvant chemotherapy (NACT) have a high risk of relapse. While adjuvant capecitabine (AdjCape) has demonstrated improved overall survival (OS) and disease-free survival (DFS) in Asian populations, its effectiveness in non-Asian settings remains uncertain. We aimed to evaluate the effect of AdjCape on survival outcomes using real-world data from a Latin American population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe conducted a retrospective cohort study (2008\u0026ndash;2024) including 360 women with non-metastatic TNBC and non-pCR treated at a single institution. Propensity score matching (PSM) was applied to adjust for baseline differences. Cox regression models assessed the association of AdjCape with OS and DFS, and stratified analyses identified subgroups with differential treatment effects.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAmong 360 patients, 106 (29.4%) received AdjCape. After PSM, 187 patients (72 AdjCape, 115 controls) were analyzed. AdjCape was not associated with improved OS (HR 0.79, 95% CI 0.51\u0026ndash;1.23, p\u0026thinsp;=\u0026thinsp;0.302) or DFS (HR 0.81, 95% CI 0.53\u0026ndash;1.23, p\u0026thinsp;=\u0026thinsp;0.321). However, significant benefit was observed in patients with high residual tumor burden (pT3\u0026ndash;pT4: OS HR 0.29, p\u0026thinsp;=\u0026thinsp;0.020; DFS HR 0.37, p\u0026thinsp;=\u0026thinsp;0.044) and in those not receiving radiotherapy (DFS HR 0.47, p\u0026thinsp;=\u0026thinsp;0.038).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eAdjCape did not improve OS or DFS in the overall TNBC non-pCR cohort but may offer benefit in patients with extensive residual disease or those not treated with radiotherapy. These findings highlight the need for individualized treatment strategies and further evaluation of capecitabine in the context of modern therapies.\u003c/p\u003e","manuscriptTitle":"Survival Impact of Adjuvant Capecitabine In Triple-Negative Breast Cancer Patients with Residual Disease: A Real-World Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-14 11:45:55","doi":"10.21203/rs.3.rs-6951831/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-25T01:53:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-24T17:26:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-16T16:30:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"259338872181451956962415716126473019905","date":"2025-07-15T13:18:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7792044756121394422784523836481742437","date":"2025-07-10T13:59:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-10T02:48:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"216151267465264007835416243391109102892","date":"2025-07-10T02:28:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-10T02:04:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-23T10:58:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-23T10:56:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"Breast Cancer Research and Treatment","date":"2025-06-23T01:34:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"breast-cancer-research-and-treatment","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brea","sideBox":"Learn more about [Breast Cancer Research and Treatment](https://www.springer.com/journal/10549)","snPcode":"10549","submissionUrl":"https://submission.nature.com/new-submission/10549/3","title":"Breast Cancer Research and Treatment","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c182d48f-b2f7-41dc-bd4a-5403de045e85","owner":[],"postedDate":"July 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-22T16:01:16+00:00","versionOfRecord":{"articleIdentity":"rs-6951831","link":"https://doi.org/10.1007/s10549-025-07814-3","journal":{"identity":"breast-cancer-research-and-treatment","isVorOnly":false,"title":"Breast Cancer Research and Treatment"},"publishedOn":"2025-09-16 15:57:37","publishedOnDateReadable":"September 16th, 2025"},"versionCreatedAt":"2025-07-14 11:45:55","video":"","vorDoi":"10.1007/s10549-025-07814-3","vorDoiUrl":"https://doi.org/10.1007/s10549-025-07814-3","workflowStages":[]},"version":"v1","identity":"rs-6951831","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6951831","identity":"rs-6951831","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}