Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women

Cancer Causes Control. 2003 Dec;14(10):933-43. doi: 10.1023/b:caco.0000007967.25865.29.


Objective: We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women.

Methods: The Women's Contraceptive and Reproductive Experiences (CARE) Study was a population-based case-control study that included 1847 postmenopausal women with incident invasive breast cancer, and 1932 control subjects, identified using random digit dialing.

Results: 45% of cases and 49% of controls used both OCs and HRT. OC users were not at increased risk regardless of subsequent HRT exposure. HRT users who had used OCs previously did not have a higher risk of breast cancer than women with no exposure to OCs. We observed a negative interaction (p-value: 0.032) of combined hormone replacement therapy (CHRT) and past OC use. The increase in risk with CHRT was stronger in women who had never used OCs in the past (odds ratio: 1.05; 95% confidence interval: 1.01-1.10 per year of exclusive CHRT use) than in women who had used OCs (odds ratio: 1.00; 95% confidence interval: 0.97-1.03).

Conclusions: We found no indication that adverse effects of exposure to OCs or HRT appeared only in the presence of the other hormone or were exacerbated by exposure to the other hormone.

Publication types

  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Breast Neoplasms / chemically induced*
  • Breast Neoplasms / epidemiology
  • California / epidemiology
  • Case-Control Studies
  • Contraceptives, Oral / adverse effects*
  • Drug Therapy, Combination
  • Estrogen Replacement Therapy / adverse effects*
  • Female
  • Georgia / epidemiology
  • Humans
  • Incidence
  • Michigan / epidemiology
  • Middle Aged
  • Pennsylvania / epidemiology
  • Postmenopause*
  • Risk Factors
  • Washington / epidemiology
  • Women's Health


  • Contraceptives, Oral