Which menopausal hormone replacement therapy (HRT) regimens have the greatest effect on breast cancer risk?

Updated: Sep 13, 2021
  • Author: Nicole K Banks, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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The WHI study demonstrated that the risk for breast cancer was 8 cases per 10,000 women per year after 5 years of therapy. This study did not show an increased risk among women who were using only estrogen. It did show a slightly reduced risk; however, the difference was not statistically significant.

These WHI findings contrast with observations from the Million Women Study, which also showed an increased risk of breast cancer in women who took estrogen alone or tibolone. However, the risk was elevated in those who received combined therapy. Neither the route nor the pattern of administration of HT had an effect on the risk of breast cancer.

A randomized, placebo-controlled study by the WHI examined the incidence of breast cancer in postmenopausal women receiving estrogen plus progestin. [12] The study included 16,608 postmenopausal women aged 50-79 years who had not undergone a hysterectomy. The study found that estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases vs 293 cases), and more deaths from all causes occurred after a breast cancer diagnosis among women who received estrogen plus progestin compared with placebo (51 vs 31).

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