What is the risk of breast cancer associated with the use of topical estrogen cream (estrogen) for the treatment of atrophic vaginitis (vaginal atrophy)?

From the Guidelines

Topical estrogen creams for atrophic vaginitis pose no significant increased risk for breast cancer, as evidenced by a large cohort study of almost 50,000 patients with breast cancer showing no higher risk of breast cancer-specific mortality in those using vaginal estrogen 1. The use of low-dose vaginal estrogen preparations, such as Estrace cream, Premarin cream, Vagifem tablets, or Estring, is considered safe for most women, including many with a history of breast cancer, due to minimal systemic absorption. Key points to consider when using topical estrogen creams for atrophic vaginitis include:

• The typical regimen involves daily application for 1-2 weeks, then maintenance dosing 2-3 times weekly
• For women with a history of estrogen-receptor positive breast cancer, consultation with an oncologist is recommended before starting treatment
• Vaginal estrogen primarily works locally to restore vaginal tissue, with blood levels of estrogen remaining within the postmenopausal range
• Non-hormonal options like vaginal moisturizers or lubricants can be tried first for women with significant concerns about estrogen exposure
• Regular follow-up with your healthcare provider is important to monitor response to treatment and address any concerns about long-term use. It is essential to weigh the benefits of treatment against potential risks, and the current evidence suggests that the benefits of topical estrogen creams for atrophic vaginitis outweigh the risks, even in women with a history of breast cancer 1.

From the FDA Drug Label

The WHI substudy of daily CE (0.625 mg)-alone provided information about breast cancer in estrogen-alone users. In the WHI estrogenalone substudy, after an average follow-up of 7. 1 years, daily CE alone was not associated with an increased risk of invasive breast cancer (relative risk [RR] 0.80). Consistent with the Women’s Health Initiative (WHI clinical trials), observational studies have also reported an increased risk of breast cancer for estrogen plus progestin therapy and a smaller, but still increased risk, for estrogen-alone therapy after several years of use

The risk of breast cancer associated with the use of topical estrogen cream (estrogen) for the treatment of atrophic vaginitis (vaginal atrophy) is not directly stated in the provided drug label for the specific context of topical estrogen use. However, based on the information provided for estrogen-alone therapy, there is no increased risk of invasive breast cancer after an average follow-up of 7.1 years.

• Key points:
  • No increased risk of invasive breast cancer with estrogen-alone therapy after 7.1 years.
  • Topical estrogen use is not directly addressed in the provided label.
  • Observational studies suggest a smaller increased risk for estrogen-alone therapy after several years of use 2

From the Research

Risk of Breast Cancer with Topical Estrogen Cream

• The risk of breast cancer associated with the use of topical estrogen cream for the treatment of atrophic vaginitis is a concern, particularly for breast cancer survivors 3, 4.
• There are no safety studies to support the use of topical vaginal estrogen in breast cancer survivors, and it is considered contraindicated by many healthcare professionals 3.
• The potential risk of breast cancer recurrence with vaginal estrogen therapy represents a long-term safety concern for patients with hormone receptor-positive breast cancer 4.
• However, some studies suggest that low-dose vaginal estrogens may be effective in treating symptoms of vaginal atrophy without causing significant proliferation of the endometrial lining, and no significant differences have been seen among vaginal preparations in terms of endometrial safety 5.

Alternatives to Topical Estrogen Cream

• Vaginal moisturizers and lubricants may be helpful alternatives for women who wish to avoid the use of hormonal therapy 3, 6.
• Vaginal moisturizers may have an equivalent efficacy to topical vaginal estrogen and should be offered to women wishing to avoid the use of hormonal therapy 3.
• Lubricants are usually used during sexual intercourse to provide temporary relief from vaginal dryness and dyspareunia, but they have no long-term therapeutic effects 3, 6.

Treatment Options

• Topical vaginal estrogen preparations reverse atrophic changes and relieve associated symptoms, while avoiding systemic effects 7.
• Current treatment guidelines for vaginal atrophy recommend the use of minimally absorbed local vaginal estrogens, along with non-hormonal lubricants or moisturizers, coupled with maintenance of sexual activity 5.
• The use of low-dose vaginal estrogens has been shown to be effective in treating symptoms of vaginal atrophy without causing significant proliferation of the endometrial lining 5.