Is topical estrogen therapy safe in patients with a history of breast cancer?

From the Guidelines

The use of topical estrogen in women with a history of breast cancer is generally considered safe for most patients, particularly low-dose vaginal estrogen preparations. Products like Vagifem (estradiol vaginal tablets), Estring (estradiol vaginal ring), or Imvexxy (estradiol vaginal inserts) are preferred options as they result in minimal systemic absorption 1. These treatments can effectively manage symptoms of vaginal atrophy, such as dryness, pain during intercourse, and recurrent urinary tract infections.

Key Considerations

• The typical regimen involves daily use for 1-2 weeks followed by maintenance therapy 2-3 times weekly.
• For women taking aromatase inhibitors or with estrogen receptor-positive breast cancers, a discussion with both an oncologist and gynecologist is strongly recommended before starting treatment 1.
• Non-hormonal options like moisturizers (Replens, Hyalo Gyn) or lubricants should be tried first.
• The safety of topical estrogen in breast cancer survivors is supported by the minimal systemic absorption of these products, with blood estrogen levels remaining within the postmenopausal range for most women using low-dose preparations 1.

Recent Guidelines

A recent study published in 2024 found that vaginal estrogen is the most effective treatment for vaginal dryness leading to sexual dysfunction and has been shown to be effective in treating itching, discomfort, and painful intercourse in postmenopausal individuals 1. Furthermore, a large cohort study of almost 50,000 patients with breast cancer followed for up to 20 years showed no evidence that there was a higher risk of breast cancer–specific mortality in those using vaginal estrogen 1.

Alternative Options

Vaginal androgens (ie, DHEA, also known as prasterone) can also be considered for vaginal dryness or pain with sexual activity, although safety data for the use of androgen-based therapy in survivors of hormonally mediated cancers are limited 1. Ospemifene, an FDA-approved selective estrogen receptor modulator (SERM), has been studied in several large trials of individuals with postmenopausal vulvar and vaginal atrophy and was found to effectively treat vaginal dryness and dyspareunia, but data in the survivor population are very limited 1.

From the FDA Drug Label

Estradiol valerate injection, USP should not be used in women with any of the following conditions: Known, suspected, or history of cancer of the breast. The use of estrogen in patients with a history of breast cancer is contraindicated, as indicated by the drug label of estradiol valerate injection, USP 2.

• The label explicitly states that estradiol valerate injection should not be used in women with a known, suspected, or history of breast cancer.
• Therefore, topical estrogen is not considered safe for use in patients with a previous history of breast cancer.

From the Research

Topical Estrogen Safety in Previous Breast Cancer

• The safety of topical estrogen therapy in patients with a history of breast cancer is a topic of ongoing debate and research 3, 4, 5, 6, 7.
• A 2013 study published in Geburtshilfe und Frauenheilkunde suggested that topical estrogen therapy may be effective in treating vaginal atrophy in breast cancer patients, but further clinical trials are needed to assess its safety 3.
• A 2018 study published in Obstetrics and Gynecology found that a small proportion of women with a history of breast cancer who were taking hormone therapy filled a topical estrogen prescription, with significant differences by type of hormone therapy 4.
• A 2025 meta-analysis published in Cancer Treatment Reviews found that the use of topical estrogen therapy during adjuvant endocrine treatment among patients with breast cancer may not increase the risk of recurrence or mortality among those treated with tamoxifen, but may convey an increased risk of recurrence among those treated with aromatase inhibitors 5.
• A 2001 study published in The Oncologist noted that estrogen replacement therapy is traditionally contraindicated in women with a previous diagnosis of breast cancer, but suggested that it may be used with caution in certain cases 6.
• A 2016 committee opinion published in Obstetrics and Gynecology stated that vaginal estrogen should be reserved for women with a history of estrogen-dependent breast cancer who are unresponsive to nonhormonal remedies, and that the decision to use vaginal estrogen should be made in coordination with a woman's oncologist 7.

Key Findings

• Topical estrogen therapy may be effective in treating vaginal atrophy in breast cancer patients 3.
• The use of topical estrogen therapy during adjuvant endocrine treatment among patients with breast cancer may not increase the risk of recurrence or mortality among those treated with tamoxifen 5.
• Nonhormonal approaches are the first-line choices for managing urogenital symptoms or atrophy-related urinary symptoms experienced by women during or after treatment for breast cancer 7.
• The decision to use vaginal estrogen should be made in coordination with a woman's oncologist and preceded by an informed decision-making and consent process 7.

Study Limitations

• Further clinical trials are needed to assess the safety of topical estrogen therapy in breast cancer patients 3, 4, 5.
• The current evidence is based on observational studies and meta-analyses, and more research is needed to fully understand the risks and benefits of topical estrogen therapy in this population 5, 6, 7.