Ovarian reserve as a measure of adjuvant chemotherapy benefit in hormone receptor positive (HR-positive), HER2-negative, node-positive breast cancer in SWOG S1007 (RxPONDER)
In brief
High anti-Müllerian hormone identifies 64% of premenopausal women who halve recurrence risk with chemotherapy
In the RxPONDER trial, premenopausal patients with baseline AMH at least 10 pg/ml (normal ovarian reserve) experienced a 54% reduction in invasive disease-free events when treated with chemotherapy plus endocrine therapy versus endocrine therapy alone (hazard ratio 0.46). By contrast, women with lower AMH showed no benefit, suggesting AMH outperforms age or menopause status for selecting chemotherapy.
- Journal
- Annals of oncology : official journal of the European Society for Medical Oncology (Q1)
- Published
- 24 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- K Kalinsky, W E Barlow, H B Pathak, R V Puri, A Mitra, T Home, et al.
- PMID
- 42613139
- DOI
- 10.1016/j.annonc.2026.05.697
Why clinicians should know about it
- Picked for Dermatology (top studies of the week, 23 August 2026): High-quality evidence in a top journal
Abstract
BACKGROUND: The phase 3 RxPONDER trial compared endocrine therapy (ET) alone or with chemotherapy (CET) in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer with recurrence score (RS) ≤25. CET benefit for the primary outcome, invasive disease-free survival (IDFS), was limited to premenopausal women who largely did not receive ovarian function suppression. In this study, we assessed hormones associated with ovarian reserve to further refine the prediction of CET benefit. PATIENTS AND METHODS: Pretreatment serum estradiol, progesterone, follicule-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and inhibin B (INHB) were assessed in a blinded fashion from 1556 participants aged <55 years. All markers used a predefined cut point. Associations with markers and IDFS and distant relapse-free survival (DRFS) were evaluated for prediction of CET benefit, adjusting for RS. Cox regression analyses of assigned treatment and its interaction with potential markers were adjusted for multiplicity. RESULTS: Baseline estradiol, progesterone, LH, and FSH were not predictive for CET benefit. AMH ≥10 pg/ml showed significant interaction with chemotherapy benefit for IDFS (Padj = 0.0034). In 64% of women with AMH ≥10 pg/ml (cut-off for normal ovarian reserve), IDFS was superior with CET compared with ET alone [hazard ratio (HR) 0.46, 95% CI 0.33-0.65, Padj = 0.00012], whereas CET was not beneficial in the 36% with low ovarian reserve (AMH <10 pg/ml; HR 1.27, 95% CI 0.81-1.99, Padj = 0.47). DRFS showed a similar pattern of results for AMH. Ultrasensitive INHB measured in the pg/ml range was also predictive of CET benefit. CONCLUSION: Among premenopausal patients aged <55 years, participants with baseline AMH <10 pg/ml did not benefit from CET. AMH was a significantly better indicator of CET benefit than menopause status, age, or other hormones. Measures of ovarian reserve may refine the selection of patients for CET.
Abstract as published, via PubMed.
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