Is mammographic breast density a breast cancer risk factor in women with BRCA mutations?

Abstract

Purpose: Increased mammographic breast density is well recognized as a breast cancer risk factor in the general population. However, it is unclear whether it is a risk factor in women with BRCA mutations. We present the results of a nested case-control screening study investigating the relationship between breast density and breast cancer incidence in this population. Patients and Methods: Women ages 25 to 65 years with known BRCA mutations were enrolled onto a single-center, high-risk breast cancer screening program. Using a computer-aided technique (Cumulus), quantitative percentage density (PD) was measured for each participant on her baseline mammogram by a single, blinded observer. Results: Between November 1997 and March 2008, 462 women (mean age, 44 years; 245 BRCA1 and 217 BRCA2) were screened and 50 breast cancers were diagnosed (38 invasive, 12 ductal carcinoma in situ [DCIS]). Density was not measured in 40 women of whom four developed cancer (three invasive, one DCIS). Mean PD (± standard deviation [SD]) for 376 women who did not develop breast cancer was 34% (23) compared with 31% (21) for 46 women with cancer (P = .51). Logistic regression model of breast cancer incidence and PD revealed an odds ratio of 0.99 (± 0.01 SD) for a one-unit increase in PD (P = .44). Results remained nonsignificant in multivariate analysis, as well as when women with pure DCIS were excluded. Conclusion: Increased mammographic breast density is not associated with higher breast cancer incidence in women with BRCA mutations. On the basis of these findings, density should not be considered a factor for these women in decision making regarding prophylactic surgery or chemoprevention. © 2010 by American Society of Clinical Oncology.