De-escalated chemotherapy and endocrine therapy outcomes in young women with stage I HR+/HER2+ breast cancer: An international real-world study.

Abstract

e12512 Background: Treatment of stage I HER2-positive breast cancer has shifted toward increased use of taxane-only chemotherapy (CT), which is associated with lower rates of treatment-related amenorrhea and other long-term toxicities. In hormone receptor–positive disease, this evolution may influence outcomes through preserved ovarian function and subsequent adjuvant endocrine therapy (ET) selection. Data focusing on ET type in young premenopausal women are limited. Methods: We identified patients with Stage I breast cancer from a retrospective international multicenter registry of premenopausal women (≤45 years) with HR+/HER2+ early breast cancer treated between 2013-2020 with (neo)adjuvant CT and ET. CT was categorized as multiagent or taxane-only. ET was categorized as tamoxifen alone, tamoxifen with ovarian function suppression (OFS), or aromatase inhibitor with OFS (AI+OFS). The primary endpoint was invasive disease-free survival (IDFS) from ET initiation. Kaplan–Meier estimates were reported at 80 months with log-rank testing. Results: Among 1,231 patients, 258 met inclusion criteria; 246 had complete follow-up data. Median age at diagnosis was 39 years (range 23-45), and median follow-up was 65.2 months (IQR 45.7-86.0). Multiagent CT (92.9% anthracycline-containing) was administered to 168/258 patients (65.1%), taxane-only regimens to 69/258 (26.7%) and CT data were unavailable for 21/258 (8.1%) patients. ET included tamoxifen alone in 117/258 (45.3%), tamoxifen+OFS in 78/258 (30.2%), and AI+OFS in 51/258 (19.8%). Over time, taxane-only CT use increased from 9% (≤2015) to 53% (≥2020), while AI+OFS use increased from 9.3% to 51.4%. Patients treated with taxane-only CT more often received trastuzumab without additional anti-HER2 therapy (100.0% vs 83.3%, p=0.001) and were more likely to receive tamoxifen alone as adjuvant ET (55.1% vs 39.9%, p=0.039). Fourteen IDFS events occurred (14/246, 5.7%); distant recurrences were uncommon (4/246,1.6%). At 80 months, IDFS was 95.0% with multiagent CT and 94.1% with taxane-only CT (p=0.21). By ET type, 80-month IDFS was 91.0% with tamoxifen alone, 97.3% with tamoxifen+OFS, and 100% with AI+OFS (p=0.18). Eighty patients (31.0%) were aged <35 years; neither treatment patterns nor 80-month IDFS differed significantly compared with older patients (91.8% vs 93.7%, p=0.17). Conclusions: In this international real-world cohort of premenopausal women with stage I HR+/HER2+ breast cancer, IDFS at 80 months was high across CT, ET, and age subgroups. As de-escalated taxane-only regimens become more common and ET strategies evolve, these data provide clinically relevant context for systemic therapy selection in young women with excellent-prognosis disease.