Combination HRT associated with increased breast cancer risk, mortality

American Pharmacist’s Association

Posted by Alex Egervary (
November 18, 2010, 1:30 pm

ENDOCRINOLOGIC DISORDERS     Frank Pucino, Section Advisor

Key point: According to 11-year mean follow-up data of more than 16,000 women from the Women’s Health Initiative (WHI) study, women who used combination hormone replacement therapy (HRT) with estrogen and progesterone during the trial were at an increased risk of developing more advanced breast cancers and dying from the disease.

Finer points: Rowan Chlebowski, MD, PhD, and colleagues published follow-up data from the WHI trial assessing the long-term effects of combination HRT on incidence of breast cancer, types of breast cancer, and breast cancer–related mortality. The original WHI trial included 16,608 postmenopausal women 50 to 79 years old without a prior hysterectomy or history of breast cancer. The women were randomized to conjugated equine estrogens 0.625 mg/d plus progesterone 2.5 mg/d (n = 8,506) or matching placebo (n = 8,102) administered from November 1993 to July 2002. The trial was halted in 2002 because the net harm of HRT exceeded the benefits.

Based on data from a mean follow-up period of 11 years, which included the postintervention phase (July 2002 to March 2005) and extension phase (April 2005 to August 2009), the investigators noted that women who received HRT during the trial were at an increased risk for invasive breast cancer (hazard ratio 1.25 [95% CI 1.07–1.46], P = 0.004), had more breast cancers with positive lymph nodes (1.78 [1.23–2.58], P = 0.03), and were more likely to die from breast cancer (1.96 [1.00–4.0], P = 0.049) compared with the placebo group. In addition, the all-cause mortality rate was higher for women in the HRT group following a breast cancer diagnosis (1.57 [1.01–2.48], P = 0.045).

What you need to know: After the WHI trial results were released in 2002, the use of HRT declined sharply in the United States, correlating with a substantial decrease in breast cancer cases. Currently, HRT is only recommended for use in small doses and for short durations of time in women with menopausal symptoms.

In an accompanying editorial, Peter Bach, MD, MAPP, cautioned that the available data do not support the safety of this approach and that the long-term negative effects of this HRT regimen are unknown. Bach recommended that women be fully informed of the risks and benefits of HRT so that they can make informed decisions. However, he noted that the “reality is that informed patient decisions are not valid when the information underlying the decision is itself speculative.” Bach added that randomized controlled trials of lower doses and shorter durations of HRT are needed to clearly determine the long-term risks of this therapy.

What your patients need to know: Educate women interested in taking combination HRT for menopausal symptoms about the risks of therapy, such as heart attack, stroke, and breast cancer, in addition to anticipated benefits. If prescribed, HRT should be given in the smallest dose for the shortest duration of time. However, patients should be informed that even with a limited regimen, the long-term risks of HRT are unknown.

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Author: Leslie Carol Botha

Author, publisher, radio talk show host and internationally recognized expert on women's hormone cycles. Social/political activist on Gardasil the HPV vaccine for adolescent girls. Co-author of "Understanding Your Mood, Mind and Hormone Cycle." Honorary advisory board member for the Foundation for the Study of Cycles and member of the Society for Menstrual Cycle Research.