In premenopausal women under the age of 55 years with hormone receptor–positive, HER2-negative, node-positive breast cancer, investigators reported that those with low baseline levels of anti-Mullerian hormone (AMH) did not benefit from adjuvant chemotherapy and endocrine therapy. The findings from an analysis of the RxPONDER trial were published in Annals of Oncology.
The researchers, including lead and co-corresponding study author Kevin Kalinsky, MD, MS, FASCO, of the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, suggested that AMH as a measure of ovarian reserve could be a significantly better biomarker for chemotherapy and endocrine therapy benefit than menopause status, age, or other hormones.
Background and Study Methods
The phase III RxPONDER trial explored the benefit of chemotherapy added to endocrine therapy in patients with hormone receptor–positive, HER2-negative, node-positive breast cancer who had a recurrence score of no more than 25, based on the 21-gene breast-cancer assay.
In the trial, added chemotherapy was only beneficial in premenopausal patients who had not received ovarian function suppression.
In this study, researchers looked to hormones (estradiol, progesterone, follicule-stimulating hormone [FSH], luteinizing hormone [LH], AMH, and inhibin B [INHB]) associated with ovarian reserve as a way to refine prediction of the benefit of added chemotherapy. They assessed the associations between biomarkers and both invasive disease-free survival and distant relapse-free survival in relation to chemotherapy/endocrine therapy benefit, with adjustment for recurrence score.
Key Findings
Baseline serum levels of estradiol, progesterone, LH, and FSH were not associated with predictive potential for chemotherapy benefit.
A significant interaction was noted between AMH levels above ≥ 10 pg/mL and chemotherapy benefit, in terms of invasive disease-free survival (adjusted P = .0034). Sixty-four percent of women had baseline serum ASH levels above ≥10 pg/mL, which was considered the cutoff for normal ovarian reserve. Among these patients, invasive disease-free survival was superior with the addition of chemotherapy vs without (hazard ratio [HR] = 0.46; 95% confidence interval [CI] = 0.33–0.65; adjusted P = .00012).
In the 36% of patients with low ovarian reserve, added chemotherapy was not beneficial in terms of invasive disease-free survival (HR = 1.27; 95% CI = 0.81–1.99; adjusted P = .47). A similar pattern of results was seen for distant relapse-free survival with AMH levels.
Ultrasensitive INHB measured in the pg/mL range was also considered predictive of added chemotherapy benefit.
In an accompanying editorial, Carmine Valenza, MD, MPH, PhD(c), and Ann H. Partridge, MD, MPH, both of the Harvard Medical School and Department of Medical Oncology, Dana-Farber Cancer Institute, noted that the main limitations of this analysis included the very low use of luteinizing hormone-releasing hormone agonist (LHRHa)-based endocrine therapy in the RxPONDER trial, suggesting that these findings are only relevant in the context of endocrine therapy with tamoxifen alone.
They did note that the assessment of ovarian reserve biomarkers has great potential as a strategy for tailoring future patient treatment recommendations. Prospective studies are needed though to further explore if AMH measurements can guide treatment decisions.
Two ongoing trials, OFSET and OPTIMA-Young, are further exploring the use of LHRHa-based endocrine therapy in patients with breast cancer.
DISCLOSURES: This work was supported in part by grants from the Breast Cancer Research Foundation, Cure in our Lifetime, the US NIH/NIGMS/NCI, Exact Sciences Corporation (previously Genomic Health, Inc.), The Hope Foundation for Cancer Research and a Consortium Agreement between the Children’s Mercy Hospital and the University of Kansas Cancer Center. For full disclosures of the study authors, visit annalsofoncology.org.
