Benefit of chemotherapy on survival in women aged ≥ 70 with HR-positive, HER2-negative breast cancer and N2-like nodal burden: A population-based analysis.

e12703 Background: High-risk localized hormone receptor (HR)-positive, HER2-negative breast cancer is often treated with chemotherapy regardless of age. We evaluated whether chemotherapy improves survival in women ≥70 with high nodal burden. Methods: This is a retrospective cohort study using SEER plus database (2000–2022) from 17 registries. Women diagnosed with non-metastatic HR–positive, HER2-negative breast cancer and 4–9 positive lymph nodes between 2010 and 2021 were included. Patients were stratified by age and categorized based on receipt of chemotherapy. The primary outcome was breast cancer–specific survival (BCSS). Covariates included age, race, tumor grade, marital status, tumor T stage, and radiation therapy. Cox models assessed the association between chemotherapy and BCSS, including age interactions. Adjusted HRs with 95% CIs are reported and p ≤ 0.05 was significant. Results: Out of 4208 female patients, 57.6% received chemotherapy. Median BCSS was longer with chemotherapy (54 vs. 45 months, HR 0.64, 95% CI 0.45–0.58, p<0.001), though the association was not significant on multivariate analysis (HR 0.90, 95% CI 0.74–1.09, p=0.27). There was significant effect modification by age (p for interaction <0.05). Among patients aged 70–74 years, chemotherapy was associated with improved survival (HR 0.65, 95% CI 0.48–0.88; p = 0.006). In contrast, no survival benefit was observed among patients aged 75–79 years (HR 1.02, 95% CI 0.77–1.35; p = 0.90) or ≥80 years (HR 1.12, 95% CI 0.82–1.52; p = 0.47). Relative to patients aged 70–74 years, the association between chemotherapy and survival was significantly attenuated in patients aged 75–79 years (interaction HR 1.56, p = 0.036) and ≥80 years (interaction HR 1.72, p = 0.018). In contrast, no evidence of effect modification was observed for hormone receptor subtype, tumor stage, receipt of radiation therapy, or histologic grade, indicating that the association between chemotherapy and survival did not differ across these tumor-related characteristics. Conclusions: In this analysis, chemotherapy improved BCSS only in women aged 70–74 with hormone receptor–positive, HER2-negative breast cancer with 4-9 lymph nodes involved. Lack of SEER data on endocrine therapy, frailty, comorbidities, treatment details, and toxicity, plus possible underreporting of chemotherapy, limits interpretation. These findings support age-informed treatment decisions and warrant validation in prospective and retrospective studies. Association between chemotherapy and breast cancer–specific survival by age group. Age group (years) Chemotherapy HR (95% CI) P value Interaction HR (95% CI) Interaction P value 70 - 74 (reference) 0.65 (0.48–0.88) 0.006 1.00 (reference) - 75 - 79 1.02 (0.77–1.35) 0.90 1.56 (1.03–2.37) 0.036 > 80 1.12 (0.82–1.52) 0.47 1.72 (1.10–2.71) 0.018