Estrogen-Progestin Found to Blunt Sensitivity of Mammography

If there weren't enough reason not to mess around with this stuff even for a short amount of time--now this!

From Medwatch

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Estrogen-Progestin Found to Blunt Sensitivity of Mammography
LOS ANGELES, Feb. 26 -- Use of estrogen plus progestin appears to make breast cancer more difficult to detect by both screening mammography and biopsy, according to a post hoc analysis of data from the Women's Health Initiative study.
Action Points 

    * Explain to interested patients that this report suggests that hormone replacement therapy may adversely impact breast cancer screening.

Although the trial was halted when it was discovered that there were most breast cancers among women randomized to estrogen-progestin, fewer of those malignancies were detected by biopsy -- 14.8% versus 19.6% in the placebo group (P=0.006), Rowan T. Chlebowski, M.D., Ph.D., of Harbor-UCLA, and colleagues, reported in the Feb. 25 issue of Archives of Internal Medicine.

Compared with controls, women in the estrogen-progestin group were about 4% more likely to have an abnormal mammogram after one year of hormone therapy and about 11% more likely to have an abnormal mammogram than women after five years of therapy (P0.001).

The cumulative frequency of mammograms with abnormalities was 35% in the hormone group versus 23% in the placebo group (P0.001), and those mammograms had less sensitivity for cancer detection, they wrote. Moreover the higher frequency of abnormal mammograms continued after hormone therapy was stopped.

The authors concluded that combined hormone therapy not only increased the risk of breast cancer, but also "compromises the diagnostic performance of mammograms and breast biopsies."

They recommended that the "usable, quantifiable estimates of the adverse effect of conjugated equine estrogens plus medroxyprogesterone acetate on breast cancer detection provided in this article should be incorporated into risk-benefit discussions with women considering even short-term use."

Wyeth Pharmaceuticals, the maker of Prempro, the estrogen-progestin pill used in the study, and Premarin, the estrogen-only pill used in a subset of women who had surgical menopause, said the "findings in this report do not change what we already know about the benefits and risks of hormone therapy."

The statement from Wyeth also noted that current labeling of both Prempro and Premarin contains "information about breast cancer risks, abnormal mammograms, and guidance regarding yearly breast examinations by a healthcare professional."

Wyeth said a key message was that, while "use of estrogen combined with progestin increased the need for repeat mammograms in this study, nearly one in four women in the placebo group also needed repeat mammograms due to abnormalities."

The Women's Health Initiative randomized 16,608 postmenopausal women to conjugated equine estrogens (0.635 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo. Mammography and breast examinations were performed at baseline and annually.

The trial was halted after 5.6 years, when the data safety monitoring board determined that women randomized to estrogen-progestin had an increased risk of breast cancer, stroke, and deep vein thrombosis, and no evidence that hormone therapy reduced the risk of heart disease.

There were 199 invasive breast cancers diagnosed among women randomized to active treatment versus 150 such cancers in the placebo arm.

Dr. Chlebowski is a consultant for AstraZeneca, Novartis, Organon, and Eli Lilly & Co., and has received grant support from Eli Lilly & Co. A co-author has served as an expert witness for Wyeth Pharmaceuticals. The Women's Health Initiative program is funded by the National Heart, Lung, and Blood Institute.

Primary source: Archives of Internal Medicine
Source reference:
Chlebowski RT, et al "Estrogen Plus Progestin and Breast Cancer Detection by Means of Mammography and Breast Biopsy"Arch Intern Med 2008; 168: 370-377.