Women with BRCA mutations face early menopause if they opt for oophorectomy to prevent ovarian cancer, but concerns about breast cancer risk have limited their use of hormone therapy to manage the symptoms.

A prospective study presented at the San Antonio Breast Cancer Symposium (SABCS) 2025 offers reassurance: Hormone therapy did not increase breast cancer risk over 5 years among BRCA carriers who opted to use it after surgical menopause vs their peers who did not use the therapy.

And among women who had undergone hysterectomy and used estrogen-only hormone therapy, breast cancer risk was actually reduced.

“We can safely use hormones when it’s indicated for this population,” said principal investigator Joanne Kotsopoulos, PhD, breast cancer researcher at the University of Toronto in Toronto, Ontario, Canada.

Guidelines recommend that women with BRCA mutations manage their high risk for ovarian cancer with surgical removal of the ovaries and fallopian tubes — before age 40 years for BRCA1 carriers and before age 45 years for BRCA2 carriers.

The resulting sudden menopause can cause severe hot flashes, night sweats, urogenital symptoms, and other issues that impair quality of life. Hormone therapy can effectively treat those symptoms, but concerns about breast cancer risk have made many physicians and patients hesitant.

Research conducted in the general population — primarily the Women’s Health Initiative — has tied hormone therapy with combined estrogen-progestin to an increased risk for breast cancer.

“It is a huge issue,” said Virginia Kaklamani, MD, breast medical oncologist at The University of Texas Health Science Center at San Antonio.

Speaking at a press briefing on the study, Kaklamani noted that surgical menopause not only triggers debilitating symptoms for many women but also may pose increased cardiovascular and bone health risks in the long term.

“So it’s nice to have data to suggest that we should be safe using hormone replacement therapy until they’re probably around [age] 50,” Kaklamani said.

The findings are based on a matched prospective analysis comparing BRCA carriers who started hormone therapy after menopause (surgical in 95% of cases) with those who did not. The researchers followed 676 pairs of women, with an average age of about 44 years, matched by gene mutation, year of birth, age at menopause, and oophorectomy status.

At enrollment, none had a history of cancer or bilateral mastectomy.

Hormone therapy included estrogen alone, progestin alone, combined estrogen-progestin, tibolone (a synthetic steroid used in some countries), and conjugated estrogen plus the selective estrogen receptor modulator bazedoxifene (Duavee, Duavive). Women used hormone therapy for an average of about 6 years.

Over a mean follow-up of 5.6 years from the start of hormone therapy, women who used the therapy had 87 incident breast cancers (12.9%) vs 128 cancers among nonusers (18.9%; P = .002).

When the researchers looked at the data by type of hormone therapy, that apparent protective effect was limited to women who used estrogen alone: Among 291 users, breast cancer risk was reduced by 63% vs their matched control individuals.

That finding is in line with the Women’s Health Initiative, which also found a decreased breast cancer risk among women who used estrogen alone. (Estrogen-only therapy is prescribed to patients who’ve had a hysterectomy, because estrogen given alone raises the risk of endometrial cancer.)

In contrast, Kotsopoulos and her team found that no other type of hormone therapy, including estrogen-progestin, was significantly associated with breast cancer risk in either direction.

However, among the 43 women who used estrogen-bazedoxifene, none developed breast cancer during follow-up compared with three cases among their matched control individuals.

It’s an interesting finding, according to Kotsopoulos, because researchers hypothesize that the breast cancer risk from combined hormone therapy stems from the progestin — and estrogen-bazedoxifene avoids that component.

“This is definitely an exciting and interesting area for future research,” Kotsopoulos said.

Among the study limitations are the relatively short follow-up and the fact that women who opted for hormone therapy might have been healthier and more engaged in activities that may decrease breast cancer, such as exercise. It is also unclear why combination hormone therapy was not associated with an increased breast cancer risk.

“There’s more to understand,” Kotsopoulos said.

The study was funded by Breast Cancer Canada and the Canadian Institutes of Health Research. Kotsopoulos reported having no conflicts of interest. Kaklamani reported being a speaker and/or consultant for AstraZeneca, Novartis, and other companies. 

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com