Using menopausal hormone therapy was not associated with an increased risk of breast cancer in women with inherited mutations in the BRCA1 or BRCA2 genes, according to the results of a matched prospective analysis presented at the 2025 San Antonio Breast Cancer Symposium (SABCS; Abstract GS3-01).
“Unfortunately, there has been a lot of reluctance and misinformation regarding menopausal hormone therapy, which is mostly attributable to findings from studies conducted in the general population (those without BRCA mutations) showing an association between menopausal hormone therapy use and an increased risk of breast cancer,” said presenting author Joanne Kotsopoulos, PhD, a scientist at the Women’s College Hospital Research and Innovation Institute and a professor at the Dalla Lana School of Public Health at the University of Toronto in Canada. “To help manage the side effects of oophorectomy safely in women with BRCA mutations, we need data from well-designed observational studies of menopausal hormone therapy use in this specific population who, due to their genetics, face elevated risks of breast cancer.”
Background and Study Methods
Menopausal hormone therapy is recommended for patients to alleviate some of the effects of surgical menopause in women who are carriers of BRCA1/2 variants and who undergo bilateral salpingo-oophorectomy at an early age to prevent the development of ovarian cancer. However, there is a concern that menopausal hormone therapy could impact the risk of breast cancer in this patient population.
Researchers conducted a prospective matched analysis—the largest prospective report of menopausal hormonal therapy and breast cancer risk to date—in women who received menopausal hormone therapy after menopause and their risk for breast cancer in carriers of BRCA variants. Women who were exposed to menopausal hormone therapy after menopause were matched 1:1 with women who did not initiate hormonal therapy according to their gene, year of birth, and age at menopause. There were a total of 676 matched pairs.
Key Findings
Among the women who were exposed to menopausal hormonal therapy, there were 87 incident cases of breast cancer (12.9%) vs 128 cases (18.9%) in those who did not receive hormonal therapy (P = .002).
A significant decrease in breast cancer risk was observed in women who received estrogen therapy vs unexposed women (hazard ratio [HR] = 0.37; 95% confidence interval [CI] = 0.24–0.57).
No adverse or protective effect was connected with the addition of progestogen to estrogen (HR = 0.94; 95% CI = 0.54–1.63), with the use of progestogen monotherapy (HR = 1.14; 95% CI = 0.21–6.22), or with tibolone monotherapy (HR = 0.57; 95% CI = 0.19–1.69).
Forty-three women received a conjugated equine estrogen plus bazedoxifene, and there were no reported cases of breast cancer in this group.
Risk findings were similar regardless of the carried genetic mutation.
“Our findings suggest that clinicians should take a personalized approach to menopause management for women with BRCA mutations who are suffering from the impact of surgical (or natural) menopause, if there are no contraindications for them,” Dr. Kotsopoulos said.
Disclosure: The study was funded by Breast Cancer Canada and the Canadian Institutes of Health Research. Dr. Kotsopoulos declared no conflicts of interest. For full disclosures of the other study authors, visit abstractsonline.com.
