Use of Estrogen and Progestin in Breast Cancer Patients

Guidelines for Managing Menopausal Symptoms After Breast Cancer: Use of Estrogen and Progestin in Breast Cancer Patients

http://www.medscape.com/viewarticle/581311_2

Use of Estrogen and Progestin in Breast Cancer Patients

Estrogen-containing hormone therapy (HT) is the most effective and well-studied treatment for menopausal vasomotor symptoms and atrophic vaginitis in healthy women,[11] but the efficacy and safety of HT following breast cancer is not established. HT was not effective in controlling hot flashes in tamoxifen users in one retrospective study.[12] Long-term use of combined HT is associated with an increased risk of new breast cancers.[13] The fall in breast cancer incidence seen after 2003 in the United States has been attributed by some to the dramatic drop in HT use following revelation from the Women's Health Initiative study that the risks of HT were not necessarily outweighed by the benefits for healthy women.[13-15] In breast cancer survivors, one randomized controlled trial (RCT) reports a three-fold increased risk of new primary or recurrent breast cancers in HT users.[16] For the two-thirds of women with hormone receptor-positive cancer, a mainstay of treatment is to block the effects of estrogen or reduce its production, and HT may compromise this effect. In addition, combined HT increases breast density, which may compromise the ability of mammography to detect early cancers.[17] Consequently, many women wish to avoid HT following breast cancer.[18] While progestins are effective for menopausal hot flashes following breast cancer,[19-21] their safety is not established. Of concern is that the addition of progestin to estrogen for HT appears to increase the risk of a primary breast cancer.[22]
Tibolone

Tibolone (Livial™, Organon NL) is a synthetic compound with weak estrogenic, progestogenic and androgenic actions. Tibolone (2.5 mg daily) effectively reduces hot flashes[23] and improves vaginal dryness in healthy postmenopausal women. Tibolone may improve sexual function more effectively than standard HT.[24] In the breast, tibolone inhibits the enzyme sulfatase, which regulates the formation of estrogens and hence decreases estrogen stimulation.[25] Tibolone inhibits proliferation of human breast cells and stimulates apoptosis in breast cancer cell lines.[26] The incidence of breast tenderness is low[27] and mammographic density does not increase with tibolone, in contrast to combined HT.[28] The relationship between tibolone use and breast cancer risk is not established. A large observational study suggested an association between tibolone and breast cancer which was less than that seen with combined HT.[29] A large prospective, randomized, placebo-controlled trial of tibolone after breast cancer has recently been halted following reports that the safety of tibolone was not equivalent to placebo (LIBERATE trial, Organon). Tibolone is available in Europe and Australia, but is not in the United States.

Given the evidence for risk or inadequate evidence for safety of available hormonal agents, these are generally avoided following breast cancer. Thus, other options are needed. This presents a clinical conundrum, as nonhormonal therapies have been reported to show only moderate efficacy in treating menopausal hot flashes,[30] and there is little research to date to inform the management of other common menopausal symptoms.

When to Consider Using Estrogen for Menopausal Symptoms Following Breast Cancer

For all women, the use of hormonal treatments for menopausal symptoms is an issue of balancing QoL against risk. For women with no history of breast cancer, the risks of HT appear minimal, particularly for low-risk women taking HT for <5 years.[13] Following breast cancer, current guidelines are to avoid estrogen and tibolone since these may increase the risk of breast cancer recurrence.[124] However, for some women, the benefits of estrogen in terms of symptom reduction and QoL may outweigh these risks.
Ultimately, the decision to take estrogen for severe menopausal symptoms should rest with the patient who is fully informed regarding the potential adverse effects on disease prognosis. A benefit of multidisciplinary care is the ability to calculate individual patient recurrence risks and to use this information in decision making about treatment choices. In addition, if endocrine therapies are producing severe menopausal symptoms with relatively small benefits in terms of recurrence or survival, the multidisciplinary (MD) team may advise that these can reasonably be stopped or adjusted. For women with advanced breast cancer, the issues of QoL are paramount and HT may be considered following discussion with her carers.