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A closer look at WHI data on hormone therapy and breast cancer risk is reassuring, and a new paradigm for osteoporosis treatment is on its way



ObGyns and their patients are the beneficiaries of a steady stream of scientific data on issues relating to menopause. In last year’s Update, I focused on the question of whether menopausal hormone therapy (HT) increases the risk of breast cancer.1 Because breast cancer continues to top the list of women’s concerns, I will use this year’s Update to assess what we have recently learned about HT and breast cancer, and to explore the latest data on nonhormonal management of vasomotor symptoms.

I am delighted that Dr. Michael McClung, an internationally recognized expert in skeletal health, has agreed to review current evidence on the prevention of osteoporotic fractures in menopausal women in the latter part of this article.

New WHI analysis confirms safety of short-term combination HT

Anderson GL, Chlebowski RT, Rossouw JE, et al. Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen and progestin. Maturitas. 2006;55:103–115.

At the annual San Antonio Breast Cancer Symposium in December, investigators presented data showing that the incidence of breast cancer in US women decreased by 7% from 2002 to 2003, a striking decline that was most prominent among women aged 50 to 69 years. The presenters speculated that the plummeting rates of HT use following publication of the initial Women’s Health Initiative (WHI) findings in the summer of 2002 (in regard to the estrogen–progestin arm2) might be responsible for this decline.3

The major media attention that followed this presentation makes one thing clear: Concerns about developing breast cancer with HT use continue to fuel anxiety among women. Although secular trend data on the national breast cancer incidence can help generate hypotheses, they cannot explain the trends. What can shed light on the association between estrogen–progestin HT and breast cancer are important new data recently released by WHI investigators.

Women new to HT had no increased risk of breast cancer

In the 2006 subgroup analysis of WHI participants in the estrogen–progestin arm, investigators focused on HT use before enrollment in the trial. Recall that in this part of the WHI, 16,608 women with an intact uterus were randomized to conjugated equine estrogen plus medroxyprogesterone acetate or placebo. Use of the study medication was stopped after a mean follow-up of 5.6 years (mean exposure to HT: 4.4 years). Overall, the risk of invasive breast cancer was slightly higher with combination HT than placebo (hazard ratio [HR] 1.24; 95% confidence interval [CI] 1.01–1.54).2

In the 2006 report from the 2002 WHI study of estrogen–progestin HT versus placebo, investigators compared the risk of being diagnosed with breast cancer in 12,297 women who had not used HT prior to study enrollment with the risk in 4,311 participants who had previously used HT. Of the previous users, 42% reported less than 2 years of use prior to WHI enrollment, and 36% reported more than 4 years of HT prior to WHI enrollment.

The findings: Among WHI participants who had never before used HT, the use of estrogen–progestin HT in the study was not associated with an elevated risk of being diagnosed with breast cancer (HR 1.02; 95% CI 0.77–1.36). However, among previous HT users, the additional use of HT in the WHI study was associated with a risk nearly double that of placebo users (HR 1.96, 95% CI 1.17–3.27).

The reassuring results of this WHI subgroup analysis received little media attention in the United States, probably because the report appeared in a journal that has low readership in this country. WHI and other findings allow us to reassure women who have undergone hysterectomy that use of unopposed estrogen has little, if any, impact on breast cancer risk in menopausal women.4,5 This new WHI subgroup analysis, along with a recent review of European and North American data,6 allows ObGyns to counsel women with an intact uterus that up to 5 years of combination estrogen–progestin hormone therapy also has little, if any, impact on breast cancer risk.

Not much to recommend among nonhormonal therapies

Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy or placebo. Ann Intern Med. 2006;145:869–879.


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