SABCS 2019 – Postmenopausal dual hormones vs estrogen alone have opposing breast cancer-related effects

  • Emily Willingham, PhD
  • Univadis
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  • Estrogen is associated with reduced breast cancer incidence in postmenopausal women undergoing hysterectomy, but progestin+estrogen is associated with an increased incidence in postmenopausal women with an intact uterus.
  • Long-term data from 2 randomized, placebo-controlled trials suggest that effects on breast cancer incidence persist for years after cessation of therapy.

Why this matters

  • Results from large observational studies have suggested that both forms of hormone therapy are tied to increased breast cancer risk and breast cancer mortality.

Study design

  • Randomized trials involved 40 US centers, beginning 1993-1998, with follow-up until 2016.
  • Enrolled women (N=27,347) were aged 50-79 years without a breast cancer history.
  • Compared with placebo, women undergoing hysterectomy received conjugated equine estrogens alone and those with an intact uterus received conjugated equine estrogens with medroxyprogesterone acetate.
  • Primary outcome: time-specific invasive breast cancer incidence rates.
  • Funding: National Institutes of Health, others.

Key results

  • With 16.1 years of cumulative follow-up, in women who have undergone hysterectomy, estrogen was associated with:
    • 23% reduced likelihood of a breast cancer diagnosis (HR, 0.77; 95% CI, 0.65-0.92);
    • 44% decreased likelihood of breast cancer-related death (HR, 0.56; 95% CI, 0.34-0.92).
  • In 18.3 years of cumulative follow-up, women with intact uterus receiving combination hormones had:
    • 29% increased likelihood of a breast cancer diagnosis: HR, 1.29 (95% CI, 1.14-1.47) and
    • no significant effect on risk for breast cancer-related mortality.


  • Presented at a conference without peer review.