Hormonal therapy for patients with breast, gynecologic cancer

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A literature search has found that the role of hormone therapy (HT) in menopausal patients with breast cancer and gynecologic malignancies is a mixed bag.

Systemic HT is not recommended for breast cancer survivors, according to the results in the journal Menopause, but vaginal low-dose estrogen appears safe.

In addition, HT can be used to treat endometrial, cervical and ovarian cancer in patients with low-risk, non-estrogen-receptor-positive subtypes.

“This review was a great opportunity to enhance our understanding of hormone therapy in special populations and to educate our colleagues on a topic that has been subject to debate,” said first author Benjamin Harris, MD, MPH, a fellow in reproductive endocrinology and infertility at Duke University.

Methods and Findings
The investigators searched MEDLINE via PubMed, yielding 1,484 citations for inclusion.

For systemic hormone therapy in women with a personal history of breast cancer, a 2005 meta-analysis of two randomized controlled trials concluded that there was more than a three-fold increase for recurrence compared to patients without HT.

The Swedish Hormonal Replacement After Breast Cancer – Is It Safe? (HABITS) randomized clinical trial (RCT) also found that breast cancer survivors on HT were 2.4 times as likely to develop additional breast cancers than patients without HT after 4 years of treatment.

For the study, continuous estrogen-progestogen therapy (EPT) or cyclic estradiol and norethisterone were the two main types of therapy.

Conversely, the Stockholm study, an RCT using predominantly cyclic progestin therapy, did not find an elevated recurrence risk after 4 years of HT.

Moreover, a recent systematic review of one RCT and three observational studies assessing the recurrence risk among premenopausal breast cancer survivors under the age of 50 using HT concluded no significant connection between HT and breast cancer recurrence risk.

Conclusions
Based on the available evidence, The North American Menopause Society (NAMS) dissuades systemic HT (ET or EPT) for breast cancer survivors, except in select cases in which the risks have been discussed with an oncologist and the failure of nonhormone options.

“Understandably, there has been much hesitation among gynecologists to prescribe vaginal estrogen to breast cancer survivors, due to the risk of systemic estrogen stimulating cancer cells and causing recurrence,” Dr. Harris told Contemporary OB/GYN. “However, the literature shows that vaginal estrogen has minimal systemic absorption that is still within postmenopausal range, and does not appear to increase breast cancer recurrences.”

A recent systematic review evaluating all the available low-dose vaginal estrogen products summarized that low-dose unopposed vaginal estrogen does not increase the risk of endometrial hyperplasia or endometrial cancer.

NAMS states that low-dose vaginal estrogen for treatment of genitourinary syndrome of menopause (GSM) can be considered for breast cancer patients who have failed nonhormone treatments, after consultation with an oncologist.

“The population of women with gynecologic malignancy who undergo menopause at an early age due to treatment, such as chemotherapy, surgery and/or radiation, is at risk for significant adverse health outcomes, including cardiovascular disease and osteoporosis, because of estrogen deficiency.” Dr. Harris said. “Although systemic HT for these women can significantly decrease those risks and improve quality of life, the therapy is not recommended in breast cancer survivors, given that the potential risk of recurrence outweighs the benefits.”

But the risks of HT should be assessed on an individual basis, with consideration for age, type of hormone therapy, dose, duration of use, regimen, route and prior exposure, according to Dr. Harris.

Disclosures:

Dr. Harris reports no relevant financial disclosures.