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.