Ovarian Reserve Markers Predict Chemotherapy Benefit in Breast Cancer

In hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, determining which premenopausal patients benefit from adjuvant chemotherapy is a major clinical challenge. Historically, clinicians relied on age and menstrual status to estimate ovarian function and predict treatment efficacy. However, a secondary analysis of the phase 3 RxPONDER trial (SWOG S1007; NCT01272037), published in Annals of Oncology, demonstrates that ovarian reserve markers—specifically anti-Müllerian hormone (AMH) and inhibin B (INHB)—predict chemotherapy benefit far more accurately than age or menstrual history.

This represents a paradigm shift for oncology nurses, who lead patient education and shared decision-making. By understanding how ovarian reserve biomarkers predict chemotherapy benefit, nurses can help patients navigate treatment options and potentially avoid unnecessary chemotherapy and its toxicities.

The Limitations of Menstrual Status and Age

In the RxPONDER trial, which enrolled 5,083 women with HR+/HER2- breast cancer, 1-3 positive nodes, and a Recurrence Score (RS) ≤25, premenopausal women derived a significant benefit from chemotherapy. However, because under 20% of these patients received ovarian function suppression (OFS), researchers hypothesized that much of the chemotherapy benefit was mediated by chemotherapy-induced menopause rather than a direct cytotoxic effect.

To investigate this, researchers analyzed pretreatment serum from 1,556 trial participants aged under 55 years to evaluate six hormones associated with ovarian reserve: estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), AMH, and INHB. The findings revealed that:

• Traditional menopausal markers—specifically baseline estradiol, progesterone, LH, and FSH—were not predictive of chemotherapy benefit.
• Chronological age and self-reported menstrual status were highly imperfect indicators of true ovarian reserve and ovarian function.
• Only AMH and INHB emerged as statistically significant, equivalent predictors of chemotherapy treatment efficacy.

AMH and Inhibin B as Predictors of Chemotherapy Benefit

The study established clear, clinically relevant thresholds for both AMH and INHB to distinguish which patients benefit from chemo-endocrine therapy (CET) versus endocrine therapy (ET) alone:

• High Ovarian Reserve (AMH ≥10 pg/ml): Approximately 64% of the analyzed cohort had normal or elevated ovarian reserve. In this group, CET led to a substantial and statistically significant improvement in invasive disease-free survival (IDFS) compared with ET alone (Hazard Ratio [HR], 0.46; 95% CI, 0.33-0.65; P_adj = 0.00012). The absolute 5-year IDFS benefit was 8.5%, and the 5-year distant relapse-free survival (DRFS) benefit was 3.8% (HR, 0.44; 95% CI, 0.28-0.69; P_adj = 0.0001).
• Low Ovarian Reserve (AMH <10 pg/ml): In the 36% of women with low ovarian reserve, adding chemotherapy to endocrine therapy offered no therapeutic benefit (IDFS HR, 1.27; 95% CI, 0.81-1.99; P_adj = 0.47; DRFS HR, 1.51; 95% CI, 0.85-2.70; P_adj = 0.27).
• Inhibin B Correlation: Using an ultra-sensitive assay with a threshold of 12 pg/ml, only participants with INHB ≥12 pg/ml derived benefit from chemotherapy (HR, 0.39; 95% CI, 0.26-0.59; P_adj = 0.0001), while those with low INHB (<12 pg/ml) did not (HR, 1.00; 95% CI, 0.70-1.43; P_adj = 0.997).

Key Takeaways for Oncology Nurses

Oncology nurses play an essential role in translating these clinical trial findings into clinical practice. Key nursing implications include:

• Refining Patient Communication: Nurses can explain to patients that chronological age is not the same as biological ovarian age. A 45-year-old patient with low AMH has a limited ovarian reserve and may derive no benefit from chemotherapy, whereas a postmenopausal patient with elevated AMH (representing 9.1% of the postmenopausal cohort in this trial) might actually benefit from chemotherapy.
• Preventing Toxicity and Improving Quality of Life: Chemotherapy carries significant short- and long-term toxicities, including cytopenias, neuropathy, cognitive changes, and cardiotoxicity. For patients with low ovarian reserve who do not benefit from chemotherapy, omitting this treatment avoids these toxicities without compromising oncologic outcomes.
• Supporting Clinical Trial Enrollment: Nurses should stay informed about ongoing trials that are prospectively addressing whether OFS can be used in lieu of chemotherapy. Key trials include the NRG-BR009 (OFSET) trial and the OPTIMA-YOUNG trial (NCT0710663), which utilizes the PAM50 assay to guide therapeutic decisions.

By incorporating baseline measures of ovarian reserve like AMH and INHB into clinical practice, oncology providers can offer highly personalized care. Oncology nurses are vital in identifying eligible patients, explaining the implications of ovarian reserve testing, and supporting patients who elect to omit chemotherapy based on their biological markers.

Reference

1. Kalinsky K, Godwin AK, Barlow WE, et al. Pretreatment ovarian reserve markers to refine prediction of chemotherapy benefit in HR-positive, HER2-negative, node-positive breast cancer: an RxPONDER trial analysis. Ann Oncol. 2026;37(5):697-708. doi:10.1016/j.annonc.2026.05.697