3D image of breast cancer metastasizing representing HER2 breast cancer.
Credit: 7activestudio/ Getty Images

Hormone replacement therapy is not generally associated with breast cancer reoccurrence, according to new research in the Journal of the National Cancer Institute. Although the study does raise a potential red flag for patients who take aromatase inhibitors. The lead author was Soren Cold of Odense University Hospital.

The study included longitudinal data from a national cohort of more than 8,000 postmenopausal women diagnosed between 1997 and 2004 with early-stage breast cancer and who received no treatment or had five years of hormone therapy, as ascertained from Denmark’s national prescription registry. Since 1995, the Danish National Prescription Database has recorded all prescriptions dispensed at Danish pharmacies. In this study, Each woman was categorized as a vaginal estrogen therapy, menopausal hormone therapy, or never-user.

“This large cohort study helps to inform the nuanced discussions between clinicians and breast cancer survivors about the safety of vaginal estrogen therapy,” said Elizabeth Cathcart-Rake, who wrote an editorial to accompany the article.

Hot flashes and night sweats, as well as vaginal dryness and urinary tract infections, often plague breast cancer survivors. These symptoms can lead patients to discontinue treatmented but may be alleviated by vaginal estrogen therapy or menopausal hormone therapy. However, the safety of systemic and vaginal estrogen use among breast cancer survivors, particularly those with estrogen receptor-positive disease, has been unclear.

Many doctors cautioned breast cancer survivors against using menopausal hormone therapy following the demonstration of an increased risk of breast cancer recurrence in two trials in the 1990s—HABITS (Hormonal Replacement After Breast Cancer – is it Safe?) and the Livial Intervention following Breast cancer: Efficacy, Recurrence, And Tolerability Endpoints trial.

In addition, a meta-analysis from the Collaborative Group on Hormonal Factors in Breast Cancer reported increased risk of primary breast cancer among women treated with menopausal hormone therapy compared with never-users, whereas vaginal estrogen therapy was not associated with an increased risk of this type of cancer.

Subsequent studies have not shown increased recurrence and these early studies had serious limitations, including small sample sizes and short follow-up periods. Therefore, it has been unclear whether vaginal estrogen therapy or menopausal hormone therapy are safe in women previously treated for breast cancer.

In this new study researchers investigated the association between hormonal treatment with the risk of breast cancer recurrence and mortality in a large cohort of Danish postmenopausal women treated for early-stage estrogen receptor-positive breast cancer. The study cohort included postmenopausal Danish women, aged 35-95 years, diagnosed with invasive early-stage nonmetastatic ER+ breast cancer from 1997 through 2004 and registered in the Danish Breast Cancer Group (DBCG) clinical database, including those who did not receive chemotherapy.

According to the paper, during a median of 9.8 years of follow-up, 1333 patients (16%) had a breast cancer recurrence. A total of 111 patients who experienced a recurrence had received vaginal estrogen therapy, 16 had received menopausal hormone therapy, and 1206 did not receive either treatment. Women who received vaginal estrogen therapy had an adjusted risk of recurrence similar to never-users. However, a subgroup analysis revealed an increased risk of recurrence, but not mortality, in patients receiving vaginal estrogen therapy with adjuvant aromatase inhibitors

“These results suggest that breast cancer survivors on tamoxifen with severe genitourinary symptoms can take vaginal estrogen therapy without experiencing an increase in their risk for breast cancer recurrence. However, caution is still advised when considering vaginal estrogen for breast cancer survivors on aromatase inhibitors, or when considering menopausal hormonal therapy,” said Cathcart-Rake.

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