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WHI investigators keep hammering the issue of hormone therapy (HT) and related increased risk of breast cancer. Their ‘money’ is actually on what they call the estrogen + progestin (E+P) users, since they cannot claim a real risk in the estrogen-alone users. So now they bring new data from the WHI observational study [1]. Here is the Abstract: 


In the WHI randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis for breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied. We identified 41,449 postmenopausal women with no prior hysterectomy and mammogram-negative within 2 years who were either not hormone users ([i]n[/i] = 25,328) or estrogen and progestin users ([i]n[/i] = 16,121). After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in non-users (0.60% vs. 0.42%, annualized rate, respectively; hazard ratio (HR) 1.55, 95% confidence interval (CI) 1.41–1.70, [i]p[/i] < 0.001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased ([i]p[/i] < 0.001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and non-users (HR 1.03, 95% CI 0.79–1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR 1.32, 95% CI 0.90–1.93, [i]p[/i] = 0.15), and more all-cause deaths after breast cancer (HR 1.65, 95% CI 1.29–2.12, [i]p[/i] < 0.001) in estrogen plus progestin users than in non-users. 


Thus the investigators concluded that, consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of non-users, increased breast cancer mortality can be expected.


  • Amos Pines, MD
    Tel-Aviv University School of Medicine, Tel-Aviv, Israel
  • Robert D. Langer, MD, MPH
    Principal Scientist and Medical Director, Jackson Hole Center for Preventive Medicine


  1. Chlebowski RT, Manson JE, Anderson GL, et al. Estrogen plus progestin and breast cancer incidence and mortality in the Womens Health Initiative observational study. J Natl Cancer Inst 2013 Mar 29. Epub ahead of print
  2. Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat 2008;107:103-11.
  3. Sturdee DW, Pines A; International Menopause Society Writing Group. Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for midlife health. Climacteric 2011;14:302-20.
  4. Langer RD. Re: Estrogen plus progestin therapy and breast cancer in recently postmenopausal women. Am J Epidemiol 2009;169:784-5
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