Breast Cancer: Topical Estrogen Risky

Study Highlights Concerns for Some Breast Cancer Patients Who Use Topical Estrogen Products

Salynn Boyles WebMD Medical News,
Reviewed By Louise Chang MD- January 25, 2006

Breast cancer patients taking drugs that block estrogen production should not use estrogen-based topical products to treat vaginal dryness and related problems, according to new research from the U.K. Estrogen-based topical drugs were found to raise levels of the estrogen-hormone estradiol in patients taking aromatase inhibitors.

The findings were published (25 Jan 06) in the online issue of the journal Annals of Oncology.

Products Perceived as Safe

Aromatase inhibitors are increasingly being used to prevent breast cancer recurrences in postmenopausal women.

Drugs such as Arimidex, Femara, and Aromasin keep breast cancers from growing by interfering with the production of estrogen.

The belief that estrogen-based drugs applied directly to the vaginal area do not raise blood levels of the hormone, or raise them only slightly, has led to the perception that the products are safe for use by breast cancer patients taking aromatase inhibitors.

But that is not what Anne Kendall, MD, and colleagues at London's Royal Marsden NHS Foundation concluded when they measured hormone levels in women on the cancer drugs who were also using commercially available vaginal products containing estrogen.

Commonly used vaginal estrogen products include Estrace and Premarin creams, and Estring and Femring vaginal rings.

"We feel strongly that women taking aromatase inhibitors should not be using vaginal estrogen therapy at the same time," Kendall tells WebMD.

Vaginal Problems Common

Aromatase inhibitors are increasingly replacing tamoxifen as a long-term follow-up therapy for postmenopausal patients with estrogen-sensitive breast cancers. Studies suggest that they are slightly more effective for preventing cancer recurrences in these patients. They have also been used for several years to treat metastatic or recurrent breast cancer, but they are used only in women who have been through menopause.

Because the drugs suppress estrogen so effectively, many women experience menopausal symptoms while taking them.

About a fifth of patients on long-term aromatase inhibitor therapy suffer from atrophic vaginitis with problems that can include severe dryness, itching, inflammation, urinary urgency, and pain during sex. Atrophic vaginitis also affects many women in their postmenopausal years.

Vaginal estrogen products are very effective in the treatment of these problems, but their impact on blood estrogen levels has not been well understood.

Kendall and colleagues measured hormone levels in six women on long-term aromatase inhibitor therapy who were also using the estrogen-based vaginal tablet Vagifem. A seventh woman who was using Premarin cream was also included in the study.

The researchers measured a "significant" rise in estradiol levels in six of seven patients two weeks after the women started vaginal treatment. Levels typically fell one month into treatment but returned to pretreatment levels in only two women over seven and 12 weeks of follow-up.

"With long-term [estrogen cream] use, women may be risking the chance that their cancer may return, although this is probably not an issue as estrogen rises for only one to two months," researcher Ian Smith, MD, says.

Lowest Dose, Shortest Time

Lubricating creams and gels that don't contain estrogen are also used to treat the vaginal problems seen in patients taking aromatase inhibitors. But Kendall concedes that they are generally not as effective as estrogen-based products.

Breast cancer specialist Clifford A. Hudis, MD, says the U.K. study shows that vaginal estrogens can raise blood estradiol levels but it does not prove that they render the estrogen-targeting cancer treatments ineffective. Hudis is chief of the Breast Cancer Medical Service at Memorial Sloan-Kettering Cancer Center in New York.

"We know that aromatase inhibitors don't always suppress estradiol in every woman to the same degree, but we don't know if the degree of suppression translates into efficacy," he says. "So it is possible that these creams don't have much of an effect." He agrees, however, that women taking aromatase inhibitors should be "strongly discouraged" from using estrogen-based vaginal creams. But he says some women may insist on using them because nothing else works for them.

"If this is the case they should be used in the lowest effective dose for the shortest time necessary," he says.

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SOURCES: Kendall, A. Annals of Oncology, 2006, online edition. Anne Kendall, MD, clinical research fellow, Royal Marsden NHS Foundation Trust, London. Clifford A. Hudis, MD, chief of the Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, New York.