Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies

Abstract

Background The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal contraceptives. Methods Individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 studies conducted in 25 countries were collected, checked, and analysed centrally. Estimates of the relative risk for breast cancer were obtained by a modification of the Mantel-Haenszel method. All analyses were stratified by study, age at diagnosis, parity, and, where appropriate, the age a woman was when her first child was born, and the age she was when her risk of conception ceased. Findings The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed (relative risk [95% Cl] in current users 1·24 [1·15-1·33], 2p<0·00001; 1-4 years after stopping 1·16 [1·08-1·23], 2p=0·00001; 5-9 years after stopping 1·07 [1·02-1·13], 2p=0·009). Second, there is no significant excess risk of having breast cancer diagnosed 10 or more years after stopping use (relative risk 1·01 [0·96-1·05], NS). The cancers diagnosed in women who had used combined oral contraceptives were less advanced clinically than those diagnosed in women who had never used these contraceptives: for ever-users compared with never-users, the relative risk for tumours that had spread beyond the breast compared with localised tumours was 0·88 (0·81-0·95; 2p=0·002). There was no pronounced variation in the results for recency of use between women with different background risks of breast cancer, including women from different countries and ethnic groups, women with different reproductive histories, and those with or without a family history of breast cancer. The studies included in this collaboration represent about 90% of the epidemiological information on the topic, and what is known about the other studies suggests that their omission has not materially affected the main conclusions.