Menopausal hormone therapy not associated with breast cancer recurrence, mortality
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Menopausal hormone therapy or vaginal estrogen therapy did not appear associated with increased risk for breast cancer recurrence or mortality among postmenopausal women with early-stage, ER-positive disease, according to study results.
However, the results, published in Journal of the National Cancer Institute, showed an increased risk for recurrence among women who received vaginal estrogen therapy with adjuvant aromatase inhibitors.
Rationale and methods
Women treated for breast cancer often receive vaginal estrogen therapy or menopausal hormone therapy to alleviate menopausal symptoms that may arise. However, the risk for breast cancer recurrence and mortality associated with hormone replacement therapy are not as clear, according to study background.
Søren Cold, MD, researcher in the department of oncology at Odense University Hospital in Denmark, and colleagues pooled longitudinal data from a national cohort of 8,461 postmenopausal Danish women diagnosed with early-stage, ER-positive nonmetastatic breast cancer between 1997 and 2004. After diagnosis, women received no hormone therapy (n = 6,371) or 5 years of vaginal estrogen therapy (n = 1,957) or menopausal hormone therapy (n = 133).
Researchers used multivariable models adjusted for potential cofounders to assess recurrence risk and mortality associated with use of vaginal estrogen therapy or menopausal hormone therapy compared with nonuse.
Median follow-up was 9.8 years for recurrence and 15.2 years for mortality.
Key findings
Results showed adjusted RR for recurrence of 1.08 (95% CI, 0.89-1.32) associated with use of vaginal estrogen therapy, 1.39 (95% CI, 1.04-1.85) among the subgroup of women who received adjuvant aromatase inhibitors and 1.05 (95% CI, 0.62-1.78) associated with use of menopausal hormone therapy.
Moreover, researchers reported adjusted HRs for overall mortality of 0.78 (95% CI, 0.71-0.87) with vaginal estrogen therapy and 0.94 (95% CI, 0.7-1.26) with menopausal hormone therapy.
“The use of vaginal estrogens seems not contraindicated for women receiving adjuvant tamoxifen or no endocrine therapy,” Cold told Healio. “Future studies that measure estrogen levels in blood in women treated with vaginal estrogens should register recurrence.”
Limitations of the study included its nonrandomized nature, researchers noted.
“Though many factors are included in the adjusted analyses, our findings may be prone to residual confounding from differences in lifestyle factors, such as nutrition, physical activity and adiposity,” they wrote. “The treatment of genitourinary syndrome of menopause in breast cancer survivors remains a challenge.”
Implications
Cold and colleagues should be commended for their inclusion of a large, population-based data set of breast cancer survivors that included records of all prescription medications given over time, which enabled the researchers to identify patients of interest, evaluate for adherence and follow outcomes for a decade, according to an accompanying editorial by Elizabeth J. Cathcart-Rake, MD, and Kathryn J. Ruddy, MD, MPH, both oncologists at Mayo Clinic in Rochester, Minnesota.
“The results of the current study help inform nuanced risk and benefit discussions between patient and oncology providers about the use of vaginal estrogen therapy in the management of genitourinary symptoms secondary to endocrine therapy,” they wrote.
References:
- Cathcart-Rake EJ, et al. J Natl Cancer Inst. 2022;doi:10.1093/jnci/djac113.
- Cold S, et al. J Natl Cancer Inst. 2022;doi:10.1093/jnci/djac112.
For more information:
Søren Cold, MD, can be reached at soeren.cold@rsyd.dk.
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