STUDY: One more nail

JOURNAL: JAMA. 2003;289:3243-3253, 3254-3263, 3304-3306

AUTHORS: Rowan T. Chlebowski, MD,

ABSTRACT: Two studies in the June 25 issue of The Journal of the American Medical Association provide more evidence against the use of combined hormone therapy (CHT) in postmenopausal women. The first study, from the Women's Health Initiative (WHI), shows that not only is the incidence of breast cancer increased with CHT, but that it is diagnosed at a more advanced stage. The second study again shows that progestin, not estrogen, is primarily responsible for the increase in breast cancer risk.

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COMMENTARY: "Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms," write Rowan T. Chlebowski, MD, PhD, from Harbor-UCLA Research and Education Institute in Torrance, California, and colleagues from the WHI Randomized Trial.

These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.

The WHI was a randomized, placebo-controlled trial of CHT in 16,608 postmenopausal women. As Medscape has reported previously, the WHI was stopped early, on July 9, 2002, when interim analysis revealed that the overall health risks associated with CHT, including breast cancer, exceeded the benefits. The present analysis determined the association of CHT with breast cancer characteristics and annual mammography findings.

After one year, the percentage of women with abnormal mammograms was 9.4% (716 of 7,656) in the CHT group and 5.4% (398 of 7,310) in the placebo group (P < .001). Throughout the study, more women receiving CHT had abnormal mammograms than did women receiving placebo.

According to the authors, about 3 million postmenopausal women in the U.S. currently use CHT, so the absolute increase in abnormal mammograms of about 4% per year with CHT is equivalent to approximately 120,000 otherwise avoidable abnormal mammograms annually in these women.

The breast cancers diagnosed in women in the [CHT] group had similar histology and grade but were more likely to have advanced stage vs. women in the placebo group.

These results suggest that invasive breast cancers developing in women receiving estrogen plus progestin therapy may have an unfavorable prognosis.

Consideration for use of estrogen plus progestin for any duration by postmenopausal women should incorporate the current findings into established and emerging risks and benefits of these agents."

In an accompanying editorial, admin H. Gann, MD, ScD, and Monica Morrow, MD, from the Feinberg School of Medicine at Northwestern University in Chicago, Illinois, refer to CHT as "a single-edged sword."

Commenting on the WHI trial, they note that "alteration of a woman's basic hormonal physiology over decades in the interest of long-term disease prevention is fraught with hazard."

They point out that CHT increases the risk of developing breast cancer while decreasing mammographic sensitivity and thereby delaying detection of the cancer.