Newswise — Researchers at The University of Kansas Cancer Center, Emory University School of Medicine and the international Southwest Oncology Group (SWOG) Cancer Research Network have identified a blood biomarker that may help thousands of women with hormone receptor-positive breast cancer avoid unnecessary chemotherapy.
Published in Annals of Oncology, the study demonstrates that measuring anti-Müllerian hormone (AMH), a marker of ovarian reserve (the number of eggs still in the ovaries), more accurately predicts which women benefit from adjuvant chemotherapy than age or menopausal status.
The research analyzed blood samples from 1,556 women younger than 55 enrolled in the landmark RxPONDER clinical trial. Investigators found that women with very low AMH levels received no measurable benefit from chemotherapy, despite being classified as premenopausal by traditional clinical criteria. In contrast, women with higher AMH levels experienced a significant improvement in invasive disease-free survival when chemotherapy was added to endocrine therapy.
“For decades we’ve relied primarily on age and menstrual history to determine menopausal status and in turn chemotherapy recommendations based on menopausal status,” said senior author Andrew K. Godwin, Ph.D., deputy director of KU Cancer Center and professor of pathology and laboratory medicine and division director of genomic diagnostics at KU Medical Center. “Our findings suggest that directly measuring ovarian reserve using ultrasensitive assays for AMH and Inhibin B provides a much more biologically meaningful assessment. This creates the opportunity to personalize treatment further and potentially spare many women the short- and long-term toxicities of chemotherapy.”
The findings build upon the original RxPONDER trial, which showed that many premenopausal women benefited from chemotherapy while postmenopausal women generally did not.
“Our current study begins to address that question,” Godwin said. “Women whose ovaries are already approaching menopause appear unlikely to derive additional benefit from chemotherapy similar to what was noted in postmenopausal patients in RxPONDER.”
Unlike commonly measured reproductive hormones such as estrogen, progesterone, follicle-stimulating hormone and luteinizing hormone, AMH remains relatively stable throughout the menstrual cycle and proves to be the strongest predictor of chemotherapy benefit. The investigators also found that Inhibin B (INHB), another marker of ovarian reserve, independently predicted benefit.
Among women with AMH levels of at least 10 picograms per milliliter, chemotherapy reduced the risk of invasive disease recurrence by more than half compared with endocrine therapy alone. Conversely, women with AMH below this threshold showed no improvement from chemotherapy. Approximately one in five premenopausal women in the study had AMH levels low enough to suggest that they could safely forgo chemotherapy.
“These results move us closer to precision medicine,” said Kevin Kalinsky, M.D., professor and division director of medical oncology at Emory University School of Medicine and principal investigator of RxPONDER. “Rather than making treatment decisions based solely on age, we may soon be able to use objective biological measurements of menopausal status to identify who truly needs chemotherapy and who does not.”
The laboratory analyses were performed by staff within the Biomarker Discovery Laboratory at KU Medical Center, where investigators measured six reproductive hormones, including highly sensitive assays capable of detecting extremely low AMH and INHB concentrations that are not measurable by many routine clinical tests. The study demonstrated that these ultrasensitive measurements outperformed traditional hormone testing for predicting treatment benefit.
“Menopausal status is an important decision-making consideration for adjuvant chemotherapy in patients with hormone-positive breast cancer,” said Priyanka Sharma, M.D., professor of medical oncology at KU Medical Center and co-author of the study. “This analysis shows that, compared to other conventional methods, AMH is a much better measure to indicate which women are truly postmenopausal. We already know postmenopausal women did not benefit from chemotherapy in the RxPONDER trial, and this sensitive AMH test gives us a more accurate way to identify women who do not benefit from chemotherapy.”
While the researchers emphasize that their findings require future clinical trials, the study provides strong evidence that ovarian reserve should be considered when selecting adjuvant therapy for younger women with hormone receptor-positive, HER2-negative breast cancer. (HER2, which stands for human epidermal growth factor receptor 2, is a protein that helps breast cancer cells grow quickly.)
“Although future studies may further refine the optimal AMH and INHB thresholds, we believe that measuring ovarian reserve before treatment should become an important part of shared decision-making between physicians and patients,” said Godwin.
At present, only a small number of clinical laboratories offer these highly sensitive AMH and INHB tests. It is critical to expand the availability of these ultrasensitive assays as more physicians incorporate them into the standard of care for these patients.
“Our goal is straightforward: to ensure that every woman receives the treatment she is most likely to benefit from while avoiding unnecessary chemotherapy and its associated toxicities,” Godwin said.
