New research indicates that a long-maligned menopausal treatment is safer than previously thought, showing that it doesn’t increase breast cancer risk in women with inherited mutations in the BRCA1 or BRCA2 genes.
Menopausal hormone therapy (MHT) is considered a first-line treatment for menopausal symptoms such as hot flashes, night sweats and vaginal dryness.
However, many women with BRCA mutations perceive MHT as unsafe, due to concerns about their already elevated breast cancer risk. Joanne Kotsopoulos, a scientist at the Women’s College Hospital Research and Innovation Institute, said these women suffer unnecessarily as a result.
“Unfortunately, there has been a lot of reluctance and misinformation regarding MHT, which is mostly attributable to findings from studies conducted in the general population (those without BRCA mutations) showing an association between MHT use and an increased risk of breast cancer,” Kotsopoulos said.
Kotsopoulos and her team analyzed data on menopausal women and their use of MHT.
Researchers created 676 matched pairs of women who did and did not use MHT to treat their menopause symptoms and carried BRCA1 or BRCA2 mutations.
Functional BRCA1 and BRCA2 genes repair damaged DNA and stop cells from becoming cancerous.
When a mutation compromises these genes, cancer risk increases. Inheriting this damaged DNA significantly raises the risk for breast and ovarian cancer in women.
Participants, aged 22 to 76 (average 43.8), took one of several MHT formulations — estrogen, progesterone, estrogen and progesterone, the synthetic hormone tibolone or conjugated estrogen and bazedoxifene (a selective estrogen receptor modulator).
Following up after an average of 5.6 years, researchers found that incidents of breast cancer were significantly less in the women who used MHT — there were 87 cases in the MHT-exposed group versus 128 cases in the non-MHT group.
While most MHT formulations were not associated with an increased or decreased risk of breast cancer, women who received estrogen-only MHT were 63% less likely to develop breast cancer than their non-MHT counterparts.
Further, none of the women who received conjugated estrogen and bazedoxifene developed cancer.
“Although based on smaller numbers, this is definitely an exciting and interesting area for future research,” said Kotsopoulos.
“Hypothetically, conjugated estrogen 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.”
Results also showed no significant differences in patients carrying a pathogenic BRCA1 or BRCA2 variant, emphasizing MHT’s safety in carriers of this 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,” said Kotsopoulos.
Kotsopoulos presented this analysis this week at the San Antonio Breast Cancer Symposium (SABCS).
MHT has had a bad rap for at least two decades. Research published in 2002 showed that MHT carries a risk of cancer and other serious conditions, which has scared off patients from taking it and doctors from prescribing it.
Subsequent research has painted a very different picture — so much so that in November, the Department of Health and Human Services announced that outdated FDA warnings will be removed from many pills, patches, injections and creams used for menopause and perimenopause symptoms.
According to Kotsopoulos, MHT could offer unparalleled relief to women with BRCA mutations who are facing the effects of early or surgical menopause.
Women with these pathogenic mutations are often advised to have their ovaries and fallopian tubes removed as a safeguard against their elevated risk of ovarian and/or fallopian tube cancer.
In younger women, the procedure can induce early menopause.
“We cannot simply recommend a drastic surgery for young women without offering a way for them to manage the well-established short- and long-term outcomes of surgical menopause,” Kotsopoulos said.
“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.”
Consistent screening is key for MHT users, and MHT is typically avoided with a history of breast cancer due to recurrence risk.
