• © 2007 by American Society of Clinical Oncology

In Reply

We thank Dr Ansink and Dr Burger for their interest in our study. They express their concern on two issues. First, they suggest that residual confounding by age at first full-term pregnancy may explain the association we found between oral contraceptive (OC) use before first full-term pregnancy and risk of breast cancer among the BRCA1/2 carriers. An earlier analysis of our cohort data showed that age at first birth was inversely related with risk of breast cancer among BRCA1 carriers, whereas no clear trend was found among BRCA2 carriers.¹ When age at first full-term pregnancy was added to the presented parity-adjusted breast cancer risk models, the results were virtually the same, and therefore, identical conclusions can be drawn. For instance, hazard ratios (HRs) changed from 1.4 (95% CI, 0.9 to 1.9) to 1.4 (95% CI, 1.0 to 2.0) and from 1.5 (95% CI, 1.1 to 2.1) to 1.7 (95% CI, 1.2 to 2.4) for less than 4 and more than 4 years of use before first full-term pregnancy among BRCA1 carriers, respectively. Among BRCA2 mutation carriers, the corresponding HRs changed from 1.2 (95% CI, 0.6. to 2.3) to 1.2 (95% CI, 0.6 to 2.4) and from 2.6 (95% CI, 1.2 to 5.5) to 2.7 (95% CI, 1.2 to 6.1) for less than 4 and more than 4 years of use before first full-term pregnancy, respectively. Moreover, we found no evidence of residual confounding by the age at first full-term pregnancy for all the other analyses presented.

Second, the authors ask to explain the finding that women who started OC use before 1975 had a lower risk of breast cancer than women who started later on. The estimated risks were, however, very similar with an HR of 1.5 (95% CI, 1.1 to 1.9) and an HR of 1.6 (95% CI, 1.2 to 2.1), for starting use before and after 1975, respectively, and as the CIs indicate, there were no statistically significant differences between these two estimates. Regretfully, data on specific brand names were not available to examine the effect of high and low dosage pill use in more detail.

We agree with the authors that our results may not be a reason to markedly change clinical guidelines on OC use for contraceptive purposes among BRCA1/2 mutation carriers. However, it has been repeatedly suggested that BRCA1/2 carriers should consider to use “the pill” as a chemopreventive agent to reduce the risk of ovarian cancer.^2,3 For this purpose, absolute safety is required, and our results suggest that this may not be guaranteed.