Adjuvant Chemotherapy in Early Triple-Negative Breast Cancer (T1a-c N0M0): A Systematic Review and Meta-Analysis.

Background: The potential benefit of adjuvant chemotherapy in patients with Stage IA triple negative breast cancer (TNBC) has not been defined. In general, patients with T1a and T1b lesions have not been included in adjuvant chemotherapy trials and the inclusion of T1c tumors has been limited. In this study using National Cancer Data Base (NCDB) we investigated the actual use of adjuvant chemotherapy in Stage IA TNBC patients relative to tumor size (T1a, T1b, T1c) and report their survival outcomes. Patients and Methods: Using NCDB we evaluated a cohort of 13,065 women with TNBC diagnosed between 2010-2012 who had American Joint Committee on Cancer Stage IA (node-negative with pathological T1a, T1b or T1c) tumors. Overall survival (OS) was the primary outcome variable. Based on the tumor size, patients were stratified on receipt of adjuvant chemotherapy or not. Patients were also stratified according to receipt of adjuvant radiation, radiation with boost, or none. Other adjusted variables included: age, race, Charlson comorbidity index, payer status, income, education, distance traveled, treating facility, and treatment delays. Multivariate Cox regression was employed to analyze the effect of adjuvant chemotherapy on overall survival. Results: The mean patient age for the entire cohort was 59.2 years (range 22-90 years), 55.8 years for the chemotherapy group, and 67.8 years for the non-chemotherapy group. There were 1275 T1a, 3197 T1b, and 7729 T1c patients. Tumor size was a very strong predictor of survival. Compared to T1a tumors, HR for death was 1.43 (95% CI: 0.86 –2.37) for T1b tumors and 3.00 (95% CI: 1.86 – 4.83) for T1c tumors. Out of all T1a, T1b, and T1c tumors in this cohort, 48.1 %, 72.6%, and 89.3% of patients received adjuvant chemotherapy respectively. A hazard ratio (HR) of death was 0.42 (95% CI: 0.31 – 0.57) for all patients who received chemotherapy compared to non-chemotherapy group. 4-year OS by tumor size and chemotherapy usage is listed in the table indicating an absolute increase of OS with adjuvant chemotherapy employment. HR for death was 0.90 (CI: 0.62 – 1.31) with use of radiation only and 0.67 (95% CI: 0.53 – 0.85) with use of radiation with boost when compared to no radiation therapy. 4-year OS (in percentage) with and without adjuvant chemotherapy use for node-negative T1a, T1b, and T1c TNBCTumor sizeNo ChemotherapyChemotherapyP ValueT1a93.78 %98.36 %0.146T1b91.91 %97.10 %<0.0001T1c80.62 %94.41 %<0.0001 Conclusion: NCDB indicated that the majority of patients with Stage IA TNBC received adjuvant chemotherapy, including 48% of patients with T1a lesions. Our data analysis demonstrated a statistically significant 4-year OS benefit in patients with T1b and T1c tumors who received adjuvant chemotherapy compared to those who did not. The survival benefit of adjuvant chemotherapy in patients with T1a tumors, however, did not reach statistical significance. Prospective randomized trials could define the potential benefits of adjuvant chemotherapy in patients with Stage IA TNBC, particularly for those with T1a and T1b tumors. Citation Format: Patel AN, Shi R, Peddi P, Burton GV. Triple negative breast cancer - Adjuvant chemotherapy use and survival outcomes in Stage IA disease [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-14-02.

576 Background: NSABP Protocol B-18 was a randomized trial which found no statistically significant difference in overall survival (OS) in patients (pts) receiving neoadjuvant (NAC) or adjuvant chemotherapy (AC), however outcome was not analyzed by breast cancer subtypes. Subsequent retrospective studies in TNBC reported conflicting results with an initial study showing a significant OS benefit with AC and later studies showing a trend toward improved survival with NAC. Furthermore, studies have not included a significant number of pts with BRCA mutations. This study aims to analyze outcomes of AC versus NAC in pts with early stage TNBC with and without BRCA germline mutations. Methods: Pts with stage I or II TNBC who had BRCA testing were identified from a prospective cohort study of 4027 pts at MD Anderson Cancer Center. Clinical, demographic, genetic test results, chemotherapy, recurrence, survival data were collected. OS and disease free survival (DFS) were estimated using the Kaplan-Meier method, and log-rank tests were used to compare groups. Results: 305 pts with stage I and II TNBC who met eligibility criteria were included in the analysis. Pts who received both NAC and AC or no chemotherapy were excluded. 181 received AC (59.3%) and 124 received NAC (40.7%). The majority of the pts were less than 50 years old (236, 77.4%) and white (194, 63.8%). 134 were BRCA positive (44.1%) and 170 were BRCA negative (55.9%). The majority of the pts received an anthracycline and taxane regimen (223, 73.1%). There was no significant association between OS or DFS and treatment with NAC versus AC in the overall cohort. Furthermore, there were no significant differences between pt subgroups (NAC BRCA positive, NAC BRCA negative, AC BRCA positive, and AC BRCA negative) with respect to either OS or DFS. Conclusions: NAC versus AC with standard anthracycline and taxane containing regimens results in similar DFS and OS survival amongst pts with stage I and II TNBC regardless of BRCA status. Further studies are needed to evaluate whether similar results are observed with newer agents, such as platinums, PARP inhibitors and other targeted agents.

e12599 Background: Neoadjuvant chemotherapy (NAC) for operable breast cancer allows for in-vivo assessment of chemotherapy response with survival and therapeutic implications. In 2017, the Capecitabine for Residual Cancer as Adjuvant Therapy (CREATE-X) trial demonstrated significant improvement in survival with the addition of adjuvant capecitabine in patients with triple negative breast cancer (TNBC) and residual disease after NAC. These results provided the rationale for NAC even in early stage TNBC. The aim of this study was to assess U.S. national rates of NAC utilization in early-stage node-negative TNBC patients before and after the release of CREATE-X and to assess factors associated with receiving NAC vs adjuvant chemotherapy (AC). Methods: The National Cancer Database was queried for women with cT1-2N0M0 TNBC from 2014–19. NAC utilization was collected and categorized as 2014-15 (pre-CREATE-X), 2016-17 (transition yrs), and 2018-19 (post-CREATE-X). Those who did not receive chemotherapy were excluded. NAC use over time was analyzed via multivariable logistic regression (MLR). Clinical and demographic factors associated with NAC vs AC utilization were assessed using ANOVA, Chi-squared, and Fisher Exact tests. A MLR model was used to determine predictors of receipt of NAC vs AC. Results: 55,633 women were treated from 2014-19: 26.9% with NAC, 52.4% with AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71yrs, respectively, p < 0.01). Most had cT1c (32.7%, n = 18,190) or cT2 (41.95%, n = 23,331) tumors and 99% had invasive ductal pathology. NAC utilization significantly increased over time, 19.5% (n = 3,465 of 17,777) in 2014-15, 27.1% (n = 5,140 of 18,985) in 2016-17, and 33.6% (n = 6,337 of 18,871) in 2018-19 (p < 0.01). On MLR analysis, increased use of NAC was associated with younger age ( < 50yrs), non-Hispanic white patients, having no comorbidities, having a cT2 tumor, grade 2 disease, and care at an academic or integrated network cancer program (p < 0.05 for all). Patients with Medicare and Medicaid insurance were less likely to receive NAC (p < 0.01). Patients who traveled > 60 miles to their treating facility were more likely to receive NAC (p < 0.01). Conclusions: From 2014–19, NAC utilization increased for patients with cT1-2N0M0 TNBC coinciding with the release of the CREATE-X results. Findings demonstrate the significance of the multidisciplinary oncology team in developing individualized treatment plans based on emerging clinical trial evidence. Racial, socioeconomic, and access disparities were observed in NAC utilization and warrants further investigation and interventions to ensure equitable care. [Table: see text]

1586 Background: There is controversy regarding the risk of recurrence of the node-negative, HER2-positive pT1a-b tumors. We have shown considerable variation in survival of HER2-positive tumors of all sizes. We now examine the HER2-positive breast cancers with regard to ER status, node-status, and tumor size. Methods: Using the California Cancer Registry 2000-2007, we studied 16,958 cases of stages 1-3, HER2-positive primary invasive breast cancer. Kaplan-Meier cause-specific 5-year overall survival (OS) was computed and the log-rank test was used to compare survival between node-positive and node-negative tumors within the T1a, T1b, T1c, and T2 categories. Cox-proportional hazards analysis was used to determine the effect of ER/PR/HER2 subtype within each tumor size category for the node-positive tumors after adjusting for age, race/ethnicity, stage, grade, and socioeconomic status. Anti-HER2 treatment information was not available. Hazard ratios (HR) and 95% confidence intervals were computed. Results: For all tumor sizes, survival was statistically significantly better for negative node-tumors than for node-positive tumors (p < 0.001). Node-negative T1a, T1b, and T1c tumors had 5-year survival of 99%, 98%, and 97% respectively. There were 7,430 node-positive cases and survival was 93% for T1a, 94% for T1b, and 90% for T1c. No variables were associated with risk of death for the T1a and T1b tumors. Compared with the ER-/PR-/HER2+ subtype (the molecularly defined HER2-positive subtype), the ER+/PR+/HER2+ (HR = 0.33; 95% CI = 0.22-0.49) and ER+/PR-/HER2+ (HR = 0.49; 95% CI = 0.30-0.81) subtypes were associated with a reduced risk of death for T1c and T2 tumors. Conclusions: It is not surprising that node-negative breast cancers have better survival than node-positive cases. We found that for HER2-positive, node-negative, T1a, T1b, and T1c tumors, 5-year OS is excellent and for node-positive cases, it is only slightly lower but still 90% or greater. For tumors less than 10mm, ER/PR/HER2 subtype does not appear to influence survival. For larger tumors, ER-positivity reduces the risk of death when compared with the molecularly defined HER2-positive subtype, suggesting that ER rather than HER2 has greater influence on OS. No significant financial relationships to disclose.

Background:Triple-negative breast cancer (TNBC), a subtype of breast cancer, due to the lack of an effective therapy target, the only postoperative approach that seems to work for TNBC is chemotherapy treatment. For TNBC that is less than 1 cm and has no lymph node metastasis, administering chemotherapy is controversial at present. The word "consider" is used in the description of the National Comprehensive Cancer Network (NCCN), and the level of evidence is IIb. The Chinese Society of Clinical Oncology (CSCO) guidelines do not provide a specific recommendation for this group of patients but recommend that all patients with TNBC should receive postoperative chemotherapy. In this study, the SEER database was used to evaluate the benefit of chemotherapy. The results will help confirm whether patients with stage T1aN0M0 and T1bN0M0 TNBC should be administered adjuvant chemotherapy.Purpose To evaluate the effect of adjuvant chemotherapy on improving the prognosis of patients with stage I triple-negative breast cancer (TNBC).Methods TNBC patients diagnosed in the SEER 18 database from 2010 to 2015 were included. Kaplan-Meier plots and log-rank tests were used to compare the differences in breast cancer-specific survival (BCSS) and overall survival (OS) between subgroups of variables. A Cox proportional hazard model was used to determine the prognostic factors affecting BCSS and OS.Results A total of 9,256 patients were enrolled in this study. Among these patients, 380 died from breast cancer, and 703 died from all causes. Patients who received chemotherapy had significantly better BCSS and OS than those who did not receive chemotherapy for stage T1cN0M0 (BCSS, hazard ratio (HR) = 0.68, 95% confidence interval (CI) = 0.51-0.90; OS, HR = 0.54, 95% CI = 0.44-0.67) and stage IB (BCSS, HR = 0.39, 95% CI = 0.16-0.95; OS, HR = 0.41, 95% CI = 0.19-0.87) disease. Patients who received chemotherapy did not have significantly better BCSS or OS than those who did not receive chemotherapy for stage T1aN0M0 or T1bN0M0 disease. The patients who received chemotherapy in the poorly differentiated and undifferentiated groups had better BCSS (HR = 0.68, 95% CI = 0.52-0.88) and OS (HR = 0.54, 95% CI = 0.44-0.66) than the patients who did not receive chemotherapy.Conclusion According to current clinical guidelines, patients with stage T1bN0M0 TNBC are probably overtreated. The prognosis of these patients with stage T1aN0M0 or T1bN0M0 disease is good enough that adjuvant chemotherapy cannot improve it further. TABLE: The effect of adjuvant chemotherapy on BCSS stratified by the tumor stageStageChemotherapyCasesDeath from breast cancerlog-rank PUnivariate CoxMultivariate CoxaHR (95%CI)PHR (95%CI)PT1aN0M00.446No857121.00(reference)1.00(reference)Yes24651.50(0.53-4.25)0.4491.17(0.33-4.12)0.808T1bN0M00.700No886281.00(reference)1.00(reference)Yes1341370.91(0.56-1.48)0.7001.00(0.57-1.74)0.999T1cN0M02.73×10-5No1410971.00(reference)1.00(reference)Yes41891710.59(0.46-0.76)3.41×10-50.68(0.51-0.90)0.007IBNo49100.0031.00(reference)1.00(reference)Yes278200.33(0.16-0.71)0.0050.39(0.16-0.95)0.038a Adjusted by age, laterality, grade, total number of malignant tumors per patient and radiotherapy.Patients who received chemotherapy had significantly better BCSS than those who did not receive chemotherapy for stage T1cN0M0 and stage IB disease. In contrast, no significant associations of chemotherapy with BCSS were observed for stage T1aN0M0 or stage T1bN0M0 disease. Citation Format: Yang Wang, Bailin Zhang. Evaluation of a beneficial effect of adjuvant chemotherapy in patients with stage I triple-negative breast cancer: A population-based study using the SEER 18 database [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-23.

e12501 Background: In general, early stage TNBC has a poor prognosis. Adjuvant chemotherapy is the gold standard therapy and different regimens have shown improved outcome. It is uncertain whether all regimens have similar efficacy and if all patients with TNBC benefit equally from treatment. Methods: We searched PUBMED to identify randomized trials between 2007 and 2017 comparing different adjuvant chemotherapy regimens in breast cancer. Only studies reporting outcomes for patients with TNBC (or hormone receptor negative disease if data on TNBC not reported) were included. The absolute differences between the experimental and the control group for 5-year disease-free survival (DFS) and overall-survival (OS) were extracted. The absolute benefit from treatment was weighted by study sample size and pooled. We then compared differences between various generations of chemotherapy. Meta-regression analysis explored the influence of study-level median follow-up, tumor size, nodal status, median age, menopausal status and generation of chemotherapy on the benefit from adjuvant chemotherapy. Results: Nineteen studies comprising of 22 comparison groups and 11306 patients with TNBC were included in the analysis. Studies comparing chemotherapy regimens of different generations showed the largest difference in 5 year DFS (weighted mean difference 7.4% for 3rd vs. 2nd generation and 5.9% for 2nd vs. 1st generation). Studies comparing chemotherapy regimens from the same generation showed smaller differences in DFS (1.9%, 1.3% and -3.5% for studies comparing 3rd, 2nd and 1st generations, respectively). The weighted differences in 5 year OS were generally lower (0.4% to 5.8%). Meta-regression results are shown in the Table. Conclusions: Later generations of adjuvant chemotherapy result in substantially improved DFS in patients with early stage TNBC with patients with larger tumor size and nodal involvement gaining most benefit irrespective of age and menopausal status. Large differences in 5 year DFS do not translate to similar effects in 5 year OS. Variable DFS β P value Median age -0.144 0.63 Menopausal 0.374 0.21 T2-T4 0.822 0.001 Node positive 0.525 0.04 Follow-up duration -0.024 0.92

Purpose: Neoadjuvant chemotherapy (NACT) is frequently used in node-positive and/or large (&amp;gt;2cm) triple-negative breast cancer (TNBC). However, there are scarce data about use and benefit of NACT in small size, node-negative TNBC. We examined survival differences of patients with T1N0 TNBC that were treated with NACT vs. adjuvant chemotherapy (ACT). Methods: This is a retrospective, cross-sectional study using data from the Surveillance, Epidemiology, and End Results database of patients with T1N0 TNBC diagnosed between 2010-2020. Logistic regression analysis was used to identify factors associated with the use of NACT. Cox regression models were used to compare overall survival (OS) for ACT and NACT cohorts, adjusting for demographic, clinicopathological, treatment and socioeconomical variables. Cumulative incidence functions (CIF) and cause-specific hazard models were used to compare the risk of breast cancer death between ACT and NACT cohorts. We also evaluated pathological complete response (pCR) rate in patients treated with NACT. Results: We found 8,146 patients treated with ACT and 1,263 patients treated with NACT. Age &amp;lt;50 years, mastectomy and radiation therapy were associated with higher odds of receiving NACT. Age &amp;gt;65 years, non-metropolitan residency, histology other than ductal, and having small tumor size were associated with lower odds of receiving NACT. When adjusted for demographic, clinicopathological, treatment, and socioeconomic covariables, NACT was associated with worse OS (HR, 1.34; 95% CI, 1.04–1.73; p=0.023) and breast cancer specific survival (BCSS) [HR, 1.52; 95% CI, 1.11–2.08; p=0.008] than ACT. The worse OS and BCSS with NACT were mainly driven by T1a tumors as patients with T1a tumors had worse OS (HR, 9.13; 95% CI, 2.40–34.75) and BCSS (HR, 19.70; 95% CI, 3.82–101.67) when treated with NACT when compared to those treated with ACT; whereas patients with T1c tumors had no difference in OS and BCSS when treated with NACT or ACT. pCR in all T1 tumors was associated with improved OS (HR, 0.28; 95% CI, 0.15 – 0.52; p&amp;lt;0.001) and BCSS (HR, 0.21; 95% CI, 0.01 – 0.46). Conclusion: Patients with T1b and T1c tumors benefit equally from the use of ACT and NACT. The reasons for worse outcome in patients with T1a tumors treated with NACT compared to ACT are unknown and need further investigation. pCR was associated with improved outcomes in patients with T1N0 TNBC who received NACT. Citation Format: Jesus D. Anampa, Alvaro Alvarez Soto, Shuwen Lin, Ana M. Bernal, Xiaonan Xue, Maja H. Oktay. Use and benefit of neoadjuvant versus adjuvant chemotherapy in node-negative, T1 triple negative breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS17-05.

We aimed to investigate the impact of radiation treatment in early-stage triple negative breast cancer (TNBC). Patients with early stage (T1-3, N0-2, M0) TNBC were identified using the New Zealand breast cancer register. The outcomes of local recurrence (LRFR), local recurrence free survival (LRFS), loco-regional recurrence free rate (LRRFR), loco-regional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), metastasis free (MFS) and overall survival (OS) were determined. Predefined univariate and multivariate cox regression analyses were used to explore associations between known prognostic and treatment factors. 1209 patients were identified with a median follow-up of 3.88years. The majority were post- menopausal. The mean tumour size was 26mm, the majority had grade III disease and a third were node positive. 625 patients had mastectomy and 584 had breast conservation surgery (BCS). 92% of BCS and 38% of mastectomy patients received radiation. 67% received adjuvant chemotherapy. The 5year OS was 77.6% (95% CI 74.6-80.2), 5year BSS was 82.1% (95%CI 79.1-84.7), 5year LRRFS was 73.9% (95% CI 73.87-73.93), 5year LRFS was 75.4 (75.37-75.43) and the 5year LRFR was 92.4% (95% CI 90.6-94.2). The significant prognostic/predictive factors for OS were adjuvant radiation treatment, chemotherapy, T stage, lymph node involvement and lympho-vascular space invasion. Results were similar for BSS, DMFS, LRFS and LRRFS except that LVSI was not significantly associated with BCSS, LRFS or LRRFS. When analysed by surgical type, in the WLE group, radiation was found to be significantly associated with improvement in all outcomes. In mastectomy group, radiation was not found to be significant for BCSS, LRFS, LRRFS or OS. Radiation treatment is significantly associated with improved outcomes in early stage TNBC. This argues against the hypothesis that TNBC has inherent radiation resistance.

Introduction: Adjuvant chemotherapy improves overall (OS) and disease-free survival in early-stage triple-negative breast cancer (TNBC) after upfront surgery. However, the role of adjuvant chemotherapy in small, node-negative TNBC has not been formally assessed in clinical trials, and high-quality data is scarce. To better understand this issue, we designed this study to evaluate the benefit of adjuvant chemotherapy in a nationwide dataset. Methods: This is a retrospective study using the National Cancer Database (NCDB). We collected data on T1N0M0 TNBC patients treated with upfront surgery diagnosed between 2010 and 2019. Kaplan-Meier methods and cox proportional models were used to compare OS between chemotherapy and no chemotherapy cohorts. Logistic regression analysis was used to identify variables associated with chemotherapy use. Results: In patients with T1N0M0 TNBC, adjuvant chemotherapy improved OS (HR, 0.51; 95% CI, 0.47 – 0.55; p&amp;lt;0.001). The benefit of adjuvant chemotherapy was evidenced across all tumor sizes but with different absolute improvements in OS; the 5- year OS rates for chemotherapy vs. no chemotherapy were 98% vs. 93%, 96% vs. 89%, and 93% vs. 80% for patients with T1a, T1b, and T1c tumors, respectively. Compared to NH white, NH Black women had the same odds of chemotherapy use (OR, 1.01; 95% CI, 0.94 – 1.10; p=0.75) but derived less benefit from chemotherapy (HR, 0.64; 95% CI, 0.54 – 0.76; p&amp;lt;0.001). Despite no difference in chemotherapy benefit in OS across age subgroups, old patients had lower odds of chemotherapy use (OR, 0.19; 95% CI, 0.18 – 0.21; p&amp;lt;0.001). Conclusions: We report that adjuvant chemotherapy improves OS in patients with T1N0M0 TNBC. However, the magnitude of the benefit is larger for T1c tumors than for T1b and T1a tumors. Patients with T1aN0 had good prognosis with or without chemotherapy; thus, informed decision-making weighing risks, benefits, and comfort level is especially critical in this group. Citation Format: Jesus Anampa, Alvaro Alvarez Soto, Samilia Obeng-Gyasi, Rachel B. Jimenez, Xiaonan Xue. Adjuvant chemotherapy in lymph node-negative, T1 triple-negative breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-11-26.

Platinum-based chemotherapy in early-stage triple negative breast cancer: A meta-analysis

BackgroundThe role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety.MethodsPubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs).ResultsA total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65–0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53–0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53–0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63–0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44–0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23–3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53–2.64, P < 0.001) and hand–foot syndrome (OR = 8.67, 95% CI 6.70–11.22, P < 0.001).ConclusionThis meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.

39 Background: Adjuvant Radiation (RT) may be omitted for elderly women with early stage breast cancer having favorable estrogen receptor status, however in the setting of triple negative breast cancer (TNBC), less evidence exists to guide decision making. As some findings thus far have shown TNBC to have an increased recurrence rate, this is an important subject to address. The purpose of this study is to use the Surveillance, Epidemiology, and End Result (SEER) database to evaluate how the addition of adjuvant radiation affects the survival of women ages 70 and above with T1-2, N0, M0 TNBC that undergo Lumpectomy (L). Methods: Cases diagnosed from 2010-2011 were downloaded from the SEER Database. Inclusion criteria were ages 70 and above, with T1-2N0M0 TNBC. Kaplan meier curves calculated overall survival (OS) and disease specific survival (DSS) in months (m). Log-Rank tests were performed to compare survival. Cox multivariate regression was performed to calculate Hazard Ratios (HR) and control for confounding variables including neoadjuvant chemotherapy, number of lymph nodes sampled, age, laterality, grade, T stage, extent of surgery, existence of other cancers. Results: From 2010-2011, SEER contained 109,559 cases of breast cancer with recorded results of Her-2-neu (H2N) status. Combining other receptor values, showed 12,620 triple-negative, which was 12% of cases. Of these, 6980 (55%) had stage T1-2, N0, M0. Lumpectomy was used in 4002 of these cases. There were 974 lumpectomy cases of women aged 70 and above. RT was given in 662 (68%) cases. After 23 months, L+ RT was associated with improved OS at 98.2% compared to 85.6% for L only (p=&lt;0.001), as well as DSS at 99% for L+RT better than 94% for L only (p=0.003). Cox Regression showed radiation demonstrated improved OS (HR=0.14, p&lt;0.001) and DSS (0.14, p=0.01). Conclusions: The use of adjuvant RT after lumpectomy for elderly women with early stage TNBC was associated with improved OS and DSS. Noting the potential for selection bias in this study, future prospective study is required to define the management of early stage triple negative breast cancer.

Background: Neoadjuvant chemotherapy (NACT) is standard of care for patients with triple-negative breast cancer (TNBC). Treatment response, especially pathologic complete response (pCR), is a strong predictive factor for treatment outcome. In the setting of up-front surgery, retrospective data have suggested improved outcome in patients with early TNBC that received breast-conserving surgery with adjuvant radiotherapy (BCT) as compared to mastectomy. Methods: We identified 2632 patients with early TNBC from the German Breast Group meta-database. Patients with cT1-2 cN0 and ypN0, available surgery and follow-up data were eligible for this project. A total of 1074 patients from 8 prospective NACT trials were analyzed. Endpoints of interest were locoregional recurrence as first site of relapse (LRR, other sites of recurrence were considered competing events), disease-free survival (DFS) and overall survival (OS); analyses were performed using univariate and multivariate Fine-Gray (for LRR) and Cox models including study, age, cT, surgery type and pCR. For the analyses including pCR as covariable, only patients at risk at the landmark time were evaluated. Results: Median age was 48 years, 69.6% of patients had cT2 tumors and 85.3% underwent BCS. Of the 1074 analyzed patients, 48.8% achieved pCR. After a median follow-up of 64 months, there were 94 (8.8%) locoregional events as first site of relapse. Upon univariate analysis, absence of pCR (hazard ratio [HR]=2.28; 95%CI 1.44-3.61; p&amp;lt; 0.001) and ypT-stage (ypT0/is vs. ypT1-3, HR=0.61; 95%CI 0.40-0.95; p=0.028) were significantly associated with LRR, while type of surgery, age and cT-stage were not. Upon multivariate analysis, absence of pCR was the only factor associated with increased risk of LRR (HR=2.22; 95%CI 1.38-3.58; p=0.001). Patients that underwent mastectomy (N=158) were significantly younger (age ≤ 50 years 72.8% vs. 59.9% for BCT [N=916]; p=0.002) DFS and OS was significantly better in patients who underwent BCT compared to mastectomy (DFS: HR=0.47; 95%CI 0.34-0.66; p&amp;lt; 0.001 and OS: HR=0.40; 95%CI 0.26-0.63; p&amp;lt; 0.001). In multivariate analysis, BCT was associated with a significantly better DFS and OS as compared to mastectomy (DFS: HR=0.51; 95%CI 0.36-0.72; p&amp;lt; 0.001; and OS HR=0.43; 95%CI 0.27-0.68; p&amp;lt; 0.001), whereas absence of pCR was associated with significantly worse DFS and OS (DFS: HR=2.43; 95%CI 1.78-3.31; p&amp;lt; 0.001; and OS: HR=3.15; 95%CI 1.94-5.10; p&amp;lt; 0.001). Conclusions: In this retrospective analysis from the GBG meta-database, treatment response, e.g. pCR, was the main determinant of locoregional recurrence in patients with early stage TNBC treated with NACT. BCT was associated with improved DFS and OS compared to mastectomy, which may at least in part reflect favorable patient selection. Citation Format: David Krug, Valentina Vladimirova, Michael Untch, Thorsten Kühn, Andreas Schneeweiss, Carsten Denkert, Beyhan Ataseven, Christine Solbach, Bernd Gerber, Hans Tesch, Michael Golatta, Sabine Seiler, Jörg Heil, Valentina Nekljudova, Sibylle Loibl. PD15-06 Pathologic complete response and breast-conserving surgery are associated with improved prognosis in patients with early-stage triple-negative breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-06.

The prognosis of patients with stage II-III Human Epidermal growth factor Receptor 2 (HER2)-positive breast cancer has significantly improved since the addition of trastuzumab to (neo-)adjuvant chemotherapy. Several reports have shown that small (≤2cm), node-negative, HER2-positive tumors have a relatively poor prognosis and these patients increasingly receive trastuzumab-based chemotherapy. We aimed to provide evidence for this approach in a population-based cohort. All T1N0M0 HER2-positive breast cancer patients diagnosed between 2006 and 2012 were identified from the Netherlands Cancer Registry. Patient, tumor, and treatment characteristics were recorded. Kaplan-Meier statistics were used for overall survival (OS) and breast cancer-specific survival (BCSS) estimations overall and in T1a, T1b, and T1c tumors separately. Cox regression analyses were performed to account for imbalances in baseline characteristics between treated and untreated patients. A total of 3512 patients were identified: 385 with T1a, 800 with T1b, and 2327 with T1c tumors. Forty-five percent of patients received chemotherapy and/or trastuzumab: 92% received both. Chemotherapy and/or trastuzumab significantly improved 8-year OS (95 vs. 84%; hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.21-0.41, P<0.001). The effect remained significant in multivariable analyses (HR 0.35; 95% CI 0.23-0.52, P<0.001). BCSS was also improved with systemic treatment in univariable (96 vs. 92%; HR 0.41; 95% CI 0.27-0.63, P<0.001) and multivariable analyses (HR 0.31; 95% CI 0.19-0.53, P<0.001). Treatment effect on OS and BCSS was similar in T1a, T1b, and T1c tumors. Chemotherapy and/or trastuzumab improves OS and BCSS and can be considered in all patients with small node-negative HER2-positive breast cancer.

Introduction/Aims: DDIR signature, HRD, and stromal tumor infiltrating lymphocytes (sTIL) have each been associated with favorable outcomes in early stage TNBC. We assessed the overlap between these markers and created prognostic categories based on their combined use in a prospective trial of TNBC patients uniformly treated with adjuvant doxorubicin (A) and cyclophosphamide (C) on the SWOG S9313 trial. Methods: SWOG S9313 trial accrued 3,125 women with early stage breast cancer to two alternative dose schedules of AC, with no difference in outcomes between the two arms. 425 centrally determined TNBC cases from S9313 were identified. DDIR signature (score ≥ 0.3681 = DDIR+, Almac Diagnostic Services), HRD status (score ≥ 42 = HRD+, Myriad Genetics), and sTIL were assessed. Gene expression data (Xcel™ array) was subjected to claraT V3.0.0 biological signature analysis (Almac Diagnostic Services), and co-expression cluster analysis was used to identify signatures associated with DDIR and HRD status. The impact of dual classification by DDIR and HRD status (Group 1: DDIR+/HRD+, Group 2: DDIR+/HRD-, Group 3: DDIR-/HRD+, Group 4: DDIR-/HRD-) on disease free survival (DFS) and overall survival (OS) was examined using Cox regression with adjustment for randomized treatment assignment and nodal status. Results: For the 425 patients, median age was 45 years, 33% were node-positive, and 5-year DFS and OS were 74% and 82%, respectively. DDIR and HRD status was available for 89% each, sTIL% was available for 99%, and all three markers were available for 77% (328/425) of patients. 60% were DDIR+ and 65% HRD+. Among DDIR- tumors, 58% were HRD+. sTIL% was associated with DDIR status (P&amp;lt;0.0001) but not with HRD status (P=0.75). The proportion of patients in each group, median sTIL%, and 5-year DFS and OS for each group are outlined in Table 1. DFS and OS were similar for Groups 1, 2, and 3 but significantly lower for Group 4. As expected, cluster analysis showed that immune response signatures dominated Groups 1 and 2 regardless of HRD status. Group 3 tumors were characterized by over-representation of genomic instability signatures, a paucity of immune-related signatures, and low sTIL infiltration. Despite this immune-depleted phenotype, the 5-year OS for Group 3 was similar to that of the immune-enriched DDIR+ groups. Signatures associated with epithelial-mesenchymal transition, mast cell infiltration, and xenobiotic metabolism were over-represented in Group 4. Conclusions: Forty percent of patients with early stage TNBC demonstrate immune-deplete (DDIR-) phenotype, and within this phenotype, more than half demonstrate HRD+ status. HRD+ status within the immune-deplete phenotype predicts for better DFS and OS with adjuvant AC, probably due to underlying genomic instability and increased sensitivity to DNA damaging chemotherapy. Sixty percent of early stage TNBC patients demonstrate an immune-enriched (DDIR+) phenotype, and this phenotype is associated with improved survival with adjuvant AC chemotherapy regardless of HRD status. These findings provide important insights for patient selection and stratification in ongoing and future trials assessing DNA damaging therapy (e.g. PARPi, anthracyclines, platinum agents), immunotherapy, and their combinations in TNBC. Table 1Immune-Enriched GroupsImmune-Deplete GroupsGroup 1 DDIR+/HRD+ N=137 (42%)Group 2 DDIR+/HRD- N=59 (18%)Group 3 DDIR-/HRD+ N=77 (23%)Group 4 DDIR-/HRD- N=55 (17%)5-year DFS82%74%74%56%P=0.001 (Group 1 vs 4); P=0.006 (Group 2 vs 4); P=0.016 (Group 3 vs 4); P=NS (Groups 1 vs 2, 1 vs 3, and 2 vs 3)5-year OS88%86%83%69%P=0.001 (Group 1 vs 4); P=0.003 (Group 2 vs 4); P=0.026 (Group 3 vs 4); P=NS (Group 1 vs 2, 1 vs 3, and 2 vs 3)Median sTIL (%)20%20%5%5%P&amp;lt;0.0001 (Group 1 vs 3); P&amp;lt;0.0001 (Group 2 vs 3); P=NS (Group 1 vs 2, 3 vs 4) Citation Format: Shane R Stecklein, William Barlow, Lajos Pusztai, Kirsten Timms, Richard Kennedy, Sunil Badve, Yesim Gökmen-Polar, Peggy Porter, Hannah Linden, Debu Tripathy, Gabriel N Hortobagyi, Andrew K Godwin, Alastair Thompson, Daniel Hayes, Priyanka Sharma. Classification of triple negative breast cancer (TNBC) by DNA damage immune response (DDIR) signature and homologous recombination deficiency (HRD) status: Analysis of SWOG S9313 adjuvant trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-05.