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by Dr. C.H. Weaver M.D. updated 9/2020

The use of hormone therapy may affect the ability of both mammography and breast biopsies to accurately diagnose breast cancer.

Postmenopausal hormone therapy with the female hormones estrogen alone or estrogen plus progestin (combined hormone therapy) effectively manages several common menopausal symptoms. However, large clinical trials conducted as part of the Women’s Health Initiative (WHI) raised concerns about the health risks of these therapies. In 2002, for example, it was reported that combined estrogen plus progestin increases the risk of breast cancer, heart disease, stroke, and blood clots. Women taking estrogen plus progestin had fewer fractures and were less likely to develop colorectal cancer, but for most women, these benefits were thought to be outweighed by the risks. Although hormone therapy increases the risk of breast cancer, it is not clear how it effects detection of breast cancer.

Impact of Combined Hormone Therapy

Researchers affiliated with the WHI recently evaluated data from the WHI trial to determine if hormone therapy affected the accuracy of diagnosis of breast cancer. The WHI trial included more than 16,000 postmenopausal women who were treated either with combined hormone therapy or placebo (inactive substitute). Data evaluated included mammography and breast examinations that were performed when the trial began and annually throughout the trial. Breast biopsies (removal of a sample of tissue for microscopic evaluation) were performed if there a suspicious area was found on mammography or clinical exam.

  • More mammograms in the group of women treated with hormone therapy revealed abnormalities compared with mammograms in the group of women who received placebo (35% versus 23%).
  • 10% of women with abnormal mammograms received subsequent biopsies compared with 6% of women in the placebo group.
  • Although the rate of breast cancer was higher among women treated with hormone therapy, biopsies diagnosed cancer with less frequency in this group of patients compared with those who received placebo.
  • In five years 10% of women had abnormalities found on mammography, while 4% underwent unnecessary biopsies that were directly attributable to hormone therapy.

Impact of Estrogen Therapy Alone

The Women’s Health Initiative trial also evaluated the use of estrogen alone in women previously treated with hysterectomy and found that the incidence of breast cancer was not increased; however, there was limited information about the effects of estrogen therapy on breast cancer detection.The Women’s Health Initiative trial randomly assigned 10,739 postmenopausal women with prior hysterectomy to receive either estrogen therapy or placebo. They performed screening mammography at baseline and annually and biopsies when indicated. The data indicated that the use of estrogen alone for five years resulted in the following:

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  • One in 11 women had an otherwise avoidable mammogram that resulted in a recommendation for short-interval follow-up.
  • One in 50 women had an otherwise avoidable breast biopsy.
  • Clinically indicated breast biopsies were more common among the estrogen users, but less commonly led to a diagnosis of breast cancer.
  • Abnormal mammograms (those suggestive of malignancy) were not increased as a result of estrogen use.
  • There was no statistically significant difference in the number of invasive breast cancers diagnosed in the two groups.

Estrogen alone does not appear to substantially compromise breast cancer detection, though it does result in some otherwise avoidable breast biopsies and short-interval follow-up mammograms.

The researchers concluded that the impact on breast cancer detection from hormone replacement with estrogen alone differs from that of combined hormone therapy with progesterone and estrogen (which results in a higher incidence of abnormal mammograms and compromised breast cancer detection).

The researchers concluded: “This adverse effect on breast cancer detection should be incorporated into risk–benefit discussions with women considering even short-term combined hormone therapy.” Postmenopausal women on hormone therapy may wish to discuss screening measures with their physician.


  1. Chlebowski T, Anderson G, Pettinger M, et al. Estrogen plus progestin and breast cancer detection by means of mammography and breast biopsy. Archives of Internal Medicine. 2008;168:370-377.
  2. Chlebowski RT, Anderson G, Manson JE, et al. Estrogen alone in postmenopausal women and breast cancer detection by means of mammography and breast biopsy. Journal of Clinical Oncology. 2010; 28: 2690-2697.
  3. Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: The Women’s Health Initiative randomized trial. JAMA. 2003; 289: 3243-3253.