Background. The MISSION Study (Menopause: Risk of Breast Cancer, Morbidity and Prevalence) is a historical-prospective study with random patient selection to determine breast cancer incidence in postmenopausal women with or without hormone replacement therapy (HRT). The first prospective follow-up phase started on 5 January 2004 and the cut-off date for data collection was 30 June 2006.

Participants. Patients were divided into two groups: an ‘exposed group’ of women on HRT regimens commonly prescribed in France or who had stopped ≤5 years previously; and an ‘unexposed group’ of women who had never received HRT or stopped >5 years previously. In total 6755 patients were included; and prospective data were available for 4949 patients: 2693 in the exposed group and 2256 in the unexposed group. Women in the exposed group were younger, less overweight, and had fewer first-degree family histories of breast cancer than women of the unexposed group. Mean duration of HRT exposure was 8.3 years, with 31% being exposed for ≥10 years.

Results. The incidence of new breast cancer cases was 0.64% in the exposed group and 0.70% in the unexposed group (relative risk RR_{exposed/unexposed} = 0.914, 95% confidence interval = 0.449–1.858; not modified when adjusted for age). Mean age at breast cancer diagnosis was similar in both groups. Breast cancer incidence in the exposed group was not significantly affected by the route of estradiol administration (cutaneous 0.69%; oral 0.52%) or HRT type (estradiol alone 0.28%; estradiol + progesterone 0.40%; estradiol + synthetic progestin 0.94%).

Conclusion. No evidence was found for an increased risk of breast cancer in women exposed to HRT compared with non-exposed women.