Menopausal hormone therapy may not increase breast cancer risk in women with BRCA mutations

HRT (hormone replacement therapy) may not increase breast cancer risk in women with BRCA mutations, new research suggests.

Women who inherit harmful mutations in the BRCA1 or BRCA2 genes, which help repair DNA, face elevated risks of ovarian and breast cancer.

They are often advised to have their ovaries and fallopian tubes surgically removed (bilateral salpingo-oophorectomy, removal of the ovaries and fallopian tubes) at relatively young ages to reduce ovarian cancer risk, but this brings on early menopause.

The study was led by Joanne Kotsopoulos, 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.

She said: “We cannot simply recommend a drastic surgery like oophorectomy for young women without offering a way for them to manage the well-established short- and long-term outcomes of surgical menopause.

“I believe we should educate patients and their health care providers on how we can safely balance the risks and benefits of MHT use to ensure longevity and improve quality of life.”

She noted there has been reluctance and misinformation regarding HRT, largely due to studies in the general population showing an association between HRT use and increased breast cancer risk.

The researchers conducted a matched prospective analysis, an observational design that pairs similar participants to mirror clinical trial conditions.

They created 676 matched pairs of women who did and did not use HRT after menopause.

Participants were matched by BRCA1 or BRCA2 status, birth year and age at menopause. The women ranged in age from 22 to 76, with an average age of 43.8.

Patients with a history of cancer, those who had received a bilateral mastectomy (removal of both breasts), and non-menopausal patients were excluded from the study.

After an average follow-up of 5.6 years, breast cancer cases were significantly lower in women who used HRT, with 87 cases in the HRT group compared with 128 cases in the non-HRT group.

Analysis by formulation showed most types of HRT were not associated with breast cancer risk.

However, two formulations were linked to decreased risk. Women who received oestrogen-only HRT were 63 per cent less likely to develop breast cancer than those who did not use HRT.

Of the 43 women who received conjugated oestrogen and bazedoxifene (a selective oestrogen receptor modulator), none developed breast cancer.

“Although based on smaller numbers, this is definitely an exciting and interesting area for future research,” Kotsopoulos said.

“Hypothetically, conjugated oestrogen and bazedoxifene could be used to mitigate breast cancer risk by avoiding progesterone, which is thought to be the breast cancer risk-associated component of MHT. Future trials will be necessary to test this hypothesis.”

There were no significant differences in results between BRCA1 and BRCA2 carriers.

“Our findings suggest that clinicians should take a personalised 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,” said Kotsopoulos.