Yaffe, Martin J.

Purpose The sensitivity of magnetic resonance imaging (MRI) for breast cancer screening exceeds that of mammography. If MRI screening reduces mortality in women with a BRCA1 or BRCA2 mutation, it is expected that the incidence of advanced-stage breast cancers should be reduced in women undergoing MRI screening compared with those undergoing conventional screening. Patients and Methods We followed 1,275 women with a BRCA1 or BRCA2 mutation for a mean of 3.2 years. In total, 445 women were enrolled in an MRI screening trial in Toronto, Ontario, Canada, and 830 were in the comparison group. The cumulative incidences of ductal carcinoma in situ (DCIS), early-stage, and late-stage breast cancers were estimated at 6 years in the cohorts. Results There were 41 cases of breast cancer in the MRI-screened cohort (9.2%) and 76 cases in the comparison group (9.2%). The cumulative incidence of DCIS or stage I breast cancer at 6 years was 13.8% (95% CI, 9.1% to 18.5%) in the MRI-screened cohort and 7.2% (95% CI, 4.5% to 9.9%) in the comparison group (P = .01). The cumulative incidence of stages II to IV breast cancers was 1.9% (95% CI, 0.2% to 3.7%) in the MRI-screened cohort and 6.6% (95% CI, 3.8% to 9.3%) in the comparison group (P = .02). The adjusted hazard ratio for the development of stages II to IV breast cancer associated with MRI screening was 0.30 (95% CI, 0.12 to 0.72; P = .008). Conclusion Annual surveillance with MRI is associated with a significant reduction in the incidence of advanced-stage breast cancer in BRCA1 and BRCA2 carriers.

Abstract Background. Breast density assessed from mammography is a strong predictor of breast cancer risk, but the strength of the association may vary with adiposity. To examine effect modification by adiposity, we combined data from four case-control studies on breast density that represented an ethnically diverse population with a wide variation in level of adiposity as measured by body mass index (BMI, kg/m2). Methods. We combined data from four case-control studies representing different locations: California, Hawaii and Minnesota in the United States, and Gifu in Japan. All studies included incident breast cancer cases diagnosed between 1994 and 2002 and matched controls representing the underlying case population. One mammographic image per subject was selected, specifically the mammogram at diagnosis for the studies from California, Minnesota, and Japan and the closest prediagnostic mammogram for Hawaii. Percent density was measured by one reader, who was blinded to case status, using a computer-assisted method. Self-reported anthropometric measures were used to classify women as normal, overweight, and obese according to ethnic-specific BMI cut points (<23, 23-27.4, and ≥27.5 for Asian women and <25, 25-29.9, and ≥30 for other ethnic groups). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) and to evaluate interactions using the likelihood ratio while adjusting for potential confounders, including age and ethnicity. Heterogeneity across studies was marginally significant as assessed by examining density-by-study interaction (P = 0.09) and, therefore, we also adjusted for study-site. Results. The study included 1,699 cases and 2,422 controls of diverse ethnicity: 45% Caucasian, 40% Asian, 9% African-American, and 7% Other. Of these women, we classified 34% as overweight and19% as obese. Age-adjusted mean percent density was significantly greater for cases than for controls: 31.7% versus 28.9%, respectively (P < 0.001). BMI was inversely associated with breast density; the estimated age-adjusted mean percent density was 36.5%, 26.8%, and 19.3% for normal, overweight, and obese, respectively (Ptrend < 0.001). The overall OR for a 10% higher percent density was 1.15 (95% CI: 1.05, 1.18) with higher estimates in overweight (OR: 1.19, 95% CI: 1.09, 1.29) and obese (OR: 1.25, 95% CI: 1.11, 1.41) than normal BMI (OR: 1.11, 95% CI: 1.05, 1.18). The effect modification by BMI was statistically significant (Pinteraction = 0.01). Conclusions. Our findings confirm that the elevated risk of breast cancer associated with breast density differs by level of adiposity, with a higher risk for overweight and obese than normal BMI. Further research is needed to understand the underlying biological reasons for these noted differences in association by adiposity. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B25.