Adjuvant Chemotherapy Use for Hormone Receptor-Positive, ERBB2-Negative Breast Cancer After RxPONDER Trial.

Importance: Since 2018, the TAILORx and RxPONDER trials have demonstrated that the 21-gene recurrence score (RS) can be indicative of the benefit of adjuvant chemotherapy in hormone receptor (HR)-positive, ERBB2 (formerly HER2)-negative breast cancer with 3 or fewer positive lymph nodes. However, its applicability to key subgroups with high risk for recurrence, including premenopausal women with positive lymph nodes and racial and ethnic minority individuals, remains unclear. Objective: To assess the temporal patterns of and disparities in adjuvant chemotherapy use in early-stage HR-positive, ERBB2-negative breast cancer by age, genomic risk, and nodal involvement. Design, Setting, and Participants: This retrospective cohort study analyzed clinical data from the 2010 to 2022 National Cancer Database. The cohort included women with stage I to III, HR-positive, ERBB2-negative breast cancer who had undergone a lumpectomy or mastectomy and were eligible for endocrine therapy. Patients were categorized into premenopausal (aged ≤50 years) or postmenopausal (aged >50 years) status. Nodal status (negative or positive) was pathologically confirmed. RS was classified per the TAILORx trial, with RS of 0 to 10 as low genomic risk, RS of 11 to 25 as intermediate genomic risk, and RS of 26 or higher as high genomic risk. Data were analyzed from January 20 to August 11, 2025. Main Outcomes and Measures: Adjuvant systemic therapy, defined as receipt of either endocrine therapy alone or chemoendocrine therapy (chemotherapy plus endocrine therapy), after surgery (lumpectomy or mastectomy). Results: A total of 504 937 women (mean [SD] age, 60.0 [10.7] years; 5.4% Hispanic, 4.3% non-Hispanic Asian or Pacific Islander, 8.1% non-Hispanic Black, 81.3% non-Hispanic White, and 0.9% other race or ethnicity) were included. Among premenopausal patients with node-negative tumors, adjuvant chemotherapy use decreased from 6.5% in 2010 to 0.9% in 2022 for those with low genomic risk and from 29.6% in 2010 to 11.1% in 2022 for those with intermediate genomic risk. However, among premenopausal patients with node-positive disease, chemotherapy use declined from 33.3% in 2010 to 12.7% in 2019 but increased to 25.7% in 2022 for the low genomic risk group. For the intermediate genomic risk group, chemotherapy use declined from 55.8% in 2010 to 38.1% in 2019 but increased to 48.9% in 2022. Among postmenopausal women, chemotherapy use for those with low to intermediate genomic risk continued to decrease from 2010 to 2022 in both node-negative and node-positive disease status. Black women with high genomic risk had lower odds of chemotherapy receipt than White women, regardless of menopausal or nodal status (adjusted odds ratio [AOR], 0.84; 95% CI, 0.78-0.90). Premenopausal Black women with low to intermediate genomic risk also had lower odds of chemotherapy receipt than White women (AOR, 0.85; 95% CI, 0.77-0.94), regardless of nodal status. Conclusions and Relevance: This retrospective cohort study found that adjuvant chemotherapy use almost doubled in premenopausal patients with node-positive tumors and with a low to intermediate genomic risk from 2019 to 2022 but decreased for patients with node-negative disease, coinciding with the publication of the TAILORx and RxPONDER trials. The findings highlight the variability in genomic assay use to facilitate adjuvant therapy recommendations for HR-positive, ERBB2-negative breast cancer.