Menopausal hormone therapy and breast cancer risk in the NIH-AARP Diet and Health Study Cohort

Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3150-60. doi: 10.1158/1055-9965.EPI-08-0435.


Background: Results from the Women's Health Initiative trial raise new questions regarding the effects of estrogen therapy (ET) and estrogen plus progestin therapy (EPT) on breast cancer risk.

Methods: We analyzed data from 126,638 females, ages 50 to 71 years at baseline, who completed two questionnaires (1995--1996 and 1996--1997) as part of the NIH-AARP Diet and Health Cohort Study and in whom 3,657 incident breast cancers were identified through June 30, 2002. Hormone-associated relative risks (RR) and 95% confidence intervals (CI) of breast cancer were estimated via multivariable regression models.

Results: Among thin women (body mass index < 25 kg/m2), ET use was associated with a significant 60% excess risk after 10 years of use. EPT was associated with a significantly increased risk among women with intact uteri, with the highest risk among current, long-term (> or = 10 years) users (RR, 2.44; 95% CI, 2.13-2.79). These risks were slightly higher when progestins were prescribed continuously than sequentially (< 15 days/mo; respective RRs of 2.76 versus 2.01). EPT associations were strongest in thin women, but elevated risks persisted among heavy women. EPT use was strongly related to estrogen receptor (ER)-positive tumors, requiring consideration of this variable when assessing relationships according to other clinical features. For instance, ER- ductal tumors were unaffected by EPT use, but all histologic subgroups of ER+ tumors were increased, especially low-grade and mixed ductal-lobular tumors.

Conclusions: Both ET and EPT were associated with breast cancer risks with the magnitude of increase varying according to body mass and clinical characteristics of the tumors.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / etiology
  • Diet
  • Estrogen Replacement Therapy / adverse effects*
  • Female
  • Humans
  • Incidence
  • Menopause
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Surveys and Questionnaires
  • United States / epidemiology