Vaginal Estrogen Therapy Safe for Women With Breast Cancer

Vaginal Estrogen Therapy Safe for Women With Breast Cancer


Women with breast cancer who use vaginal estrogen therapies, such as tablets or creams, do not face an increased risk for breast cancer–specific mortality, which can provide some reassurance to patients and providers that vaginal estrogen therapies are safe in this population.


  • Vaginal estrogen therapy can effectively treat symptoms of genitourinary syndrome of menopause — symptoms that many women with breast cancer experience and which may lead to endocrine therapy noncompliance. It remains unclear, however, whether vaginal estrogen therapy can affect breast cancer recurrence or mortality in this patient population.

  • To investigate, the researchers used UK cancer registries to identify women aged 40-79 years who were diagnosed with breast cancer in Scotland and Wales, gathering data on cancer stage, grade, treatment, presence of anemia, among other factors. Hormone receptor status was included for women in Scotland and smoking status and body mass index were included for women in Wales.

  • The research team wanted to determine whether the risk for breast cancer–specific mortality was higher in women who used vaginal estrogen therapy vs those who did not use hormone replacement therapy.

  • Using national mortality records, the researchers calculated rates of breast cancer–specific mortality up to June 2019 in Scotland, for a median follow-up of 5 years, and June 2020 in Wales, for a median follow-up of 8 years.


  • Overall, the analysis included 49,237 women with breast cancer; over the study period, 5795 breast cancer–specific deaths occurred.

  • After a breast cancer diagnosis, 5% of women used vaginal estrogen therapy and 2% received systemic hormone replacement therapy.

  • Compared with women who did not receive hormone replacement therapy, those who used vaginal estrogen therapy showed no increased risk for breast cancer–specific mortality; in fact, these women may have had a slightly lower risk for breast cancer–specific mortality (hazard ratio [HR], 0.77; P = .01).

  • The authors observed no increased risk for breast cancer–specific mortality in the vaginal estrogen therapy cohort among patients who received five or more vaginal estrogen therapy prescriptions (HR, 0.57), those receiving higher-dose vaginal estrogen therapy (HR, 0.81; P = .31), those with estrogen receptor–positive breast disease (HR, 0.88; 95% CI, 0.62-1.25), or those who received aromatase inhibitors (HR, 0.72; 95% CI, 0.58-0.91).


“In the absence of trials of vaginal estrogen therapy in breast cancer, the findings of this study provide some reassurance that patients with breast cancer who received vaginal estrogen therapy were not at a markedly higher risk of breast cancer–specific mortality,” the team concluded, adding that the results also “appear to support [UK] national guidelines suggesting that vaginal estrogen therapy can be considered for genitourinary symptoms if nonhormonal treatments are unsuccessful.”


The study, led by Chris R. Cardwell, PhD, from the Centre for Public Health at Queen’s University Belfast, was published online in JAMA Oncology on November 2.


The authors acknowledge that the study was limited by their inability to confirm the degree of medication adherence among the participants, and by the relatively short duration of follow-up. The researchers also noted that they could not control for certain potential confounding factors, such as physical activity and menopausal status, and they could not determine whether women who received treatment for genitourinary syndrome of menopause had lower estradiol levels and/or better compliance to endocrine therapies.


The study was supported by grants from Cancer Research UK. Cardwell declared relationships with Cancer Research UK outside of the current work. Another author declared relationships with Roche, Lilly, MSD, AstraZeneca, BD, Novartis, and others.

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