Hormone replacement therapy containing progestins and given continuously increases breast carcinoma risk in Sweden

Cancer. 2003 Mar 15;97(6):1387-92. doi: 10.1002/cncr.11205.


Background: The authors previously reported an increased risk of breast carcinoma with longer duration of hormone replacement therapy (HRT) use. It is unclear if different types of HRT confer different risks.

Methods: In this study, a population-based cohort of 29,508 women were interviewed during 1990-1992 to determine whether there are any differences in breast carcinoma risk according to different types and duration of HRT use.

Results: At the end of the follow-up period in December 2001, the cohort constituted 298,649 person-years. Slightly more breast carcinoma cases were seen (n = 556) than expected (n = 508.37; standardized morbidity ratio =1.09, 95% confidence interval [CI] = 1.00-1.19). Approximately 3663 women had ever used HRT. In Cox regression models, time to breast carcinoma in relation to duration and type of HRT use was analyzed, adjusting for age at menarche, age at first full-term pregnancy, parity, age at menopause, family history of breast carcinoma, and age at interview. In women with a natural menopause, a significantly higher risk was observed for longer duration of combined continuous HRT use compared with never users (hazard ratio [HR] = 4.60, 95% CI = 2.39-8.84). Nonsignificant elevated risks also were observed for longer combined sequential (HR = 2.23, 95% CI = 0.90-5.56), gestagen only (HR = 3.74,9 5% CI = 0.94-14.97), and estriol use (HR = 1.89, 95% CI = 0.81-4.39). No increased risk was seen in women after 5 years of nonuse. When studying women who ever used only one type of HRT, even more elevated HRs for gestagen-containing preparations were seen. The highest risks were associated with the combined continuous and gestagen-only therapy in women with >/= 48 months of use. Use of estradiol without progestins did not increase breast carcinoma risk significantly. The authors estimated the cumulative risk of breast carcinoma in a 50-year-old woman with gestagen-containing therapies for >/= 48 months, with a follow-up of 10 years, to be 7% (95% CI = 5.4-11.4%) compared with 2% (95% CI = 1.6%-2.9%) for never-users of HRT.

Conclusions: Longer use of HRT containing progestins significantly elevates breast carcinoma risk whereas estradiol use does not. Continued use of progestins rendered the highest risks. The yearly risk of breast carcinoma for long-term users of progestins is of the magnitude of 50% the risk of a BRCA1 mutation carrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / etiology*
  • Carcinoma / epidemiology
  • Carcinoma / etiology*
  • Cohort Studies
  • Estradiol / administration & dosage
  • Estradiol / adverse effects
  • Female
  • Hormone Replacement Therapy / adverse effects*
  • Humans
  • Middle Aged
  • Progestins / administration & dosage
  • Progestins / adverse effects*
  • Risk Factors
  • Sweden / epidemiology
  • Time Factors


  • Progestins
  • Estradiol