Is Vaginal Estrogen Safe for Women Who Have Had Breast Cancer?

Breast cancer treatment can leave women with many side effects that impair quality of life afterward. These include vaginal dryness, itching and pain during intercourse caused by declining estrogen levels. 

Concerns About Cancer Recurrence

Vaginal dryness, itching and painful intercourse can seriously affect psychological and physical health. Although vaginal estrogen can relieve these symptoms, there are substantial concerns about its safety after breast cancer. In particular, for patients with hormone receptor-positive (HR-positive) tumors and those taking aromatase inhibitors, the possibility that estrogen may increase the risk of cancer recurrence has prompted debate among clinicians and patients. Understanding the effects on long-term breast cancer survival is therefore crucial to using vaginal estrogen safely.

A New Study

A French study presented on 17 May 2024 at the ESMO Breast Cancer Congress found no increased recurrence risk with vaginal estrogen in women with hormone receptor (HR)-negative breast cancer or women taking tamoxifen concurrently for HR-positive tumors. However, the study suggested that vaginal estrogen should be avoided in women taking aromatase inhibitors.

Study Details

Women treated for breast cancer may develop genitourinary symptoms such as vaginal dryness, itching and painful intercourse because of lower estrogen levels. Vaginal estrogen therapies such as estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol) can prevent these symptoms, but their effects on breast cancer outcomes are uncertain. Researchers designed a study using French insurance data to assess the effect on disease-free survival after breast cancer.

The median age was 54; 85% had HR-positive and 15% HR-negative tumors. Researchers performed subgroup analyses by HR status and endocrine treatment regimen.

Results

• Of 135 thousand patients, 1739 used vaginal estrogen: 56% promestriene, 34% estriol and 10% both.
• Starting vaginal estrogen in patients with HR-positive tumors led to a modest decline in disease-free survival, particularly with concurrent aromatase inhibitor treatment (a reduction of 2.1 percentage points over 5 years).
• No reduction in disease-free survival was observed in patients with HR-negative tumors or those treated with tamoxifen.
• Among aromatase inhibitor users, starting estriol caused a "more severe and earlier" decline in disease-free survival than starting promestriene (a reduction of 4.2 percentage points over 3 years, versus a difference of 1.0 percentage points with promestriene).

Commentary

This study addresses an important quality-of-life issue in cancer: sexual dysfunction, which is associated with anxiety and depression and should be recognized as a major component of quality of life. The results suggest that vaginal estrogen is safe for women with HR-negative tumors and those receiving tamoxifen concurrently. However, it should be avoided whenever possible in women taking aromatase inhibitors; in this group, promestriene should be preferred to estriol.

Several factors may explain these results:

1. Hormonal Mechanisms: Estrogen is known to stimulate tumor growth in women with HR-positive tumors. Tamoxifen blocks its effects, whereas aromatase inhibitors reduce estrogen production. The extent to which vaginal estrogen enters systemic circulation and how these hormones affect tumor cells may directly influence outcomes.
2. Treatment Regimens: Tamoxifen and aromatase inhibitors work differently: tamoxifen blocks estrogen receptors, while aromatase inhibitors prevent estrogen production. These differences alter the effects of vaginal estrogen.
3. Individual Factors: Genetic makeup, tumor characteristics and general health may influence outcomes. Each patient's treatment plan should therefore be assessed individually.

These findings indicate that vaginal estrogen requires careful evaluation in women treated for breast cancer. More safety research is needed, but current findings are promising for those with HR-negative tumors and those taking tamoxifen. A more cautious approach is needed for women treated with aromatase inhibitors.