| Summary: | Abstract Background Validation studies of the 21‐gene recurrence score (RS) previously demonstrated that adjuvant chemotherapy plus endocrine therapy (CET) was associated with a significant survival benefit in women with node negative breast cancer (BC) and RS >31. However, the TAILORx trial, did not quantify the benefit of adjuvant CET in older women with node negative hormone receptor positive (HR+) BC with RS ≥26. We hypothesized that CET would be associated with improved overall survival (OS) compared to endocrine therapy (ET) in women >50 with HR+/HER2‐node negative BC and RS ≥26. Methods The National Cancer Database (NCDB) was queried to identify women >50 with RS ≥26 ER+/HER2‐BC pT1‐2N0M0. Chi‐square and logistic regression analysis determined the difference between ET and CET. OS was analyzed using a multivariable Cox model. Results We included 16,745 women—4740 (28.3%) received ET and 12,005 (71.7%) received CET. Women who received CET had: moderately (OR = 1.853, p < 0.001) or poorly/undifferentiated tumors (OR = 3.875, p < 0.001), pT2 (OR = 1.356, p < 0.001), or lymph‐vascular invasion (OR = 1.206, p = 0.001). After accounting for demographic and oncologic factors, 5‐year OS rates were significantly superior in women receiving CET vs. ET alone (95.4% vs. 92.0%, Hazard Ratio = 0.680, p < 0.001). Conclusions We observed that CET was associated with a clinically and statistically significant higher OS compared to ET alone in women >50 years of age with RS ≥26 pT1 and pT2 N0M0 HR+/HER2‐breast cancer, and which suggests that cytotoxic chemotherapy has an impact on reducing mortality that is independent of induction of premature ovarian failure.
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