A prospective study of different types of hormone replacement therapy use and the risk of subsequent breast cancer: the women's health in the Lund area (WHILA) study (Sweden)

Cancer Causes Control. 2003 Sep;14(7):673-80. doi: 10.1023/a:1025635720208.


Objectives: Reports suggest that combined estrogen plus progestin hormone replacement therapy (HRT) confers a higher breast cancer risk than estrogen alone. We aimed to establish whether breast cancer risk depends on the type of HRT formula.

Methods: The cohort consisted of 6586 women, aged 50-64 years, from the Lund area, Sweden, with no reported breast cancer upon inclusion. We obtained information such as HRT use through a questionnaire between December 1995 and February 2000. New breast cancers were identified through the South Swedish tumor registry.

Results: Between inclusion and December 2001, 101 women developed breast cancer. Only ever use of the continuous combined estrogen plus progestin (CCEP) formula differed between cases and controls (45.2% versus 23.5%; p = 0.000001). Compared with never users, exclusive CCEP users had the highest age-adjusted hazard ratio HR 3.3 (95% CI: 1.9-5.6; p < 0.001), followed by users of CCEP in addition to other HRT formulas HR 2.8 (95% CI: 1.4-5.5; p = 0.003). No significant increase was seen in women who exclusively used other HRT formulas.

Conclusion: Women who used CCEP had over three times the risk of developing breast cancer compared with never users and twice the risk compared with users of other types of HRT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / epidemiology*
  • Case-Control Studies
  • Chi-Square Distribution
  • Estrogens / adverse effects
  • Female
  • Hormone Replacement Therapy / adverse effects*
  • Humans
  • Middle Aged
  • Progestins / adverse effects
  • Proportional Hazards Models
  • Prospective Studies
  • Registries
  • Risk Factors
  • Surveys and Questionnaires
  • Sweden / epidemiology


  • Estrogens
  • Progestins