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by Dr. C.H. Weaver M.D. updated 4/2022

According to research published in the Archives of Internal Medicine, postmenopausal women who experience new pain in their breasts while taking hormone replacement therapy may have an increased risk of developing breast cancer.

As women reach menopause and beyond, more than 80% will experience symptoms such as hot flashes, night sweats, sleep disturbance, and vaginal dryness. Postmenopausal hormone therapy that includes estrogen can relieve these symptoms, but the risks and benefits of hormone therapy must be carefully weighed for each woman.

Breast CancerConnect 490

Previous reports suggest that the combination of estrogen plus progestin, for example, increases the risk of breast cancer, heart disease, stroke, and blood clots, but decreases the risk of colorectal cancer and bone fractures.

Dense breast tissue is a risk factor for developing breast cancer. Women with the majority of their breasts comprised of dense breast tissue are at a significantly higher risk of developing breast cancer than women who do not have dense breast tissue.

Researchers from California analyzed data from the Postmenopausal Estrogen-Progestin Interventions Mammographic Density Study. This study included 594 women aged 45 to 64 years of age. Results from mammography scans were evaluated at the initiation of the trial, as well as at 12 months follow-up. Women were either treated with hormone replacement therapy or placebo (inactive substitute).

  • Women taking hormone replacement therapy with new onset breast pain had a nearly 4% increase in breast tissue density.
  • Women taking hormone replacement therapy who did not experience new breast pain had only a 0.6% increase in breast tissue density.
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To further explore the relationship between new-onset breast tenderness during hormone therapy and risk of breast cancer, researchers evaluated information from the WHI trial of combined estrogen plus progestin. The study enrolled more than 16,000 women between the ages of 50 and 79. Half the women received combined hormone therapy and half received a placebo.

The analysis focused on women who did not report breast tenderness at the start of the study. Information about new-onset breast tenderness was collected one year into the study.

  • New-onset breast tenderness was reported by 36.1% of women in the hormone group and 11.8% of women in the placebo group.
  • Among women in the hormone group, those who reported new-onset breast tenderness were 48% more likely to develop breast cancer than those who did not report new-onset breast tenderness.
  • Among women in the placebo group, new-onset breast tenderness was not related to risk of breast cancer.

The researchers concluded that new onset breast pain while taking hormone replacement therapy is associated with an increase in breast tissue density. Since breast tissue density is associated with an increased risk of breast cancer, these results indicate that new onset breast pain may ultimately be associated with an increased risk of breast cancer among postmenopausal women taking hormone replacement therapy.

These results suggest new-onset breast tenderness during postmenopausal hormone therapy with combined estrogen plus progestin may indicate an increased risk of breast cancer.

  1. Crandall C, Karlamangla A, Huang M-H, et al. Association of New-Onset Breast Discomfort with an Increase in Mammographic Density During Hormone Therapy. Archives of Internal Medicine. 2006;166:1578-1584.
  2. Crandall CJ, Aragaki AK, Chlebowski RT et al. New-onset breast tenderness after initiation of estrogen plus progestin therapy and breast cancer risk. Archives of Internal Medicine. 2009;169:1684-1691.