Higher rate of abnormal mammograms in women on combined HT

Women considering combined hormone therapy should be counseled about the risks vs. benefits due to the adverse effect the therapy has on breast cancer detection.

A team of researchers from the Women’s Health Initiative conducted a trial to determine the effect of combined HT on breast cancer detection. Post-menopausal women (n=16,608) were randomly assigned to receive conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or to receive placebo. Breast examinations, including mammography, were performed each year.

Researchers evaluated mammography results for 5.6 years of treatment to determine its effects on cancer detection. The overall frequency of abnormal mammograms was higher in the HT group than in placebo (35% vs. 23%; P<.001). Breast biopsies in the HT group diagnosed cancer less frequently than in the placebo group (14.8% vs. 19.6%, P=.006), despite a greater increase in breast cancers and diagnosis at higher stages in the HT group, the researchers wrote.

Those assigned to combined HT had an approximate 4% greater risk of an abnormal mammogram after one year and an approximate 11% greater risk after five years, compared with placebo. – by Stacey L. Adams

Arch Intern Med. 2008;168:370-377.

The researchers report ancillary findings of the WHI with an eye to understanding how conjugated equine estrogen plus medroxyprogesterone acetate for approximately five years affected the ability to diagnose breast cancer. Recall that the reason this arm of the WHI was stopped was because of greater relative risk of invasive breast cancer and a higher incidence of stage 2B or greater cancers compared to placebo.

The findings are not surprising given our understanding of how estrogen and progestin in combination is associated with more breast density. Unfortunately, assessing breast density was not planned for in the WHI. The findings don't help us with estrogen-only therapy. The WHI, however, also found that there was no increase in mammograms suspicious or highly suggestive of malignancy in the active arm. Prior work suggests that these changes happen when estrogen is coupled with a progestin necessary to avoid increased endometrial cancer risk from unopposed estrogen alone. Current prescriptions most commonly use lower doses of estrogens and progestins (when the uterus is present), and alternative preparations and route of delivery are more commonplace.

We have also improved our screening capability with more experience and with better technology. Currently, screening methods are being studied to determine how best to deal with breast density given that it is more common in younger patients and those in need of hormone treatment when the risk-benefit suggests it is needed. Many physicians avoid mammography in patients with dense breasts and use alternative screening methods. Optimum strategies are yet to be understood. The delivery and the methodology are improving all the time. I have consistently discussed the problem of more dense breasts leading to more difficulty with diagnosis. These findings don't change that discussion. The quantitative risk can't be transferred precisely to current risk-benefit discussions. On the other hand, it is nice to see that it has been quantified for this dose. It is one more bit of information that helps us inform our patients better. It is unfortunate that only one preparation and one dose of estrogen and progestin were used in the WHI randomized controlled trial.

– Robert A. Wild, MD, PhD, MPH

Professor of Reproductive Endocrinology
Oklahoma University Health Sciences Center, Oklahoma City