Mammographic density does not differ between unaffected BRCA1/2 mutation carriers and women at low-to-average risk of breast cancer.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #5002 Background: Mammographic density (MD) is one of the strongest risk factors for sporadic breast cancer. Since MD is a non-invasive, reproducible and quantitative measure, it has been proposed as a compelling intermediate marker in studies aimed at understanding breast cancer etiology and prevention. The mechanism by which MD influences breast cancer risk is unknown. However, epidemiologic evidence suggests that dense breast tissue may be, in part, genetically regulated. Increased MD has been positively associated with family history of breast cancer. Family studies of sisters, including twins, provide further support for a genetic influence on MD. The relationship between MD and BRCA1/2 mutation status is equivocal. Methods: We examined whether MD differed between unaffected BRCA1/2 mutation carriers ages 22-55 enrolled in the Clinical Genetics Branch's Breast Imaging Study (n=143) and women at low-to-average risk of breast cancer ages 25-79 enrolled in the same study (n=29) or the National Naval Medical Center's Susceptibility to Breast Cancer Study (n=90). Low-to-average risk women were defined as being BRCA mutation-negative members of mutation-positive families; or women with no personal history of breast cancer, a Pedigree Assessment Tool score <8 (i.e., low risk of a hereditary breast cancer syndrome) and a Gail score <1.7. Participants from both studies had standardized, quantitative calculations of MD measured by the same experienced radiologist (CKC). Percent MD was calculated from digitized mammograms using a computerized method developed at NCI. Standard breast cancer risk factor information was collected from all subjects. Results: MD values were normally distributed. The intraclass correlation coefficient for MD assessed blindly in 100 paired sets was 0.889. The mean age of BRCA mutation carriers was 38.0 vs. 48.4 in low-to-average risk women. The unadjusted mean percent MD was higher in women with BRCA1/2 mutations compared with women at low-to-average breast cancer risk (37.3% vs. 33.4%; p=0.04). There was no difference in MD after adjusting for age and body mass index (35.1% vs. 36.3%; p=0.48). We explored age at menarche, nulliparity, age at first birth, menopausal status, number of breast biopsies, and exposure to exogenous hormonal agents as covariates of potential interest with regard to modulating MD. Taking these factors into account did not substantially alter the results of the age-/BMI-adjusted analysis. Conclusion: Our results do not provide support for an independent effect of BRCA1/2 mutation status on mammographic density. We are currently investigating whether novel quantitative characteristics imbedded within the breast parenchyma in mammographic images (e.g., texture and contrast) may have a stronger correlation with mutation status. Our goal is to identify imaging features which might more accurately classify women with regard to their breast cancer risk status. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5002.