Changes in mammographic density over time in breast cancer cases and women at high risk for breast cancer.

High mammographic breast density is one of the strongest intermediate markers of breast cancer risk, and decreases in density over time have been associated with decreases in breast cancer risk. Using repeated measures of mammographic density in a cohort of high-risk women, the Women at Risk (WAR) cohort at Columbia University Medical Center (N = 2670), we examined whether changes in prediagnostic mammographic density differed among 85 prospectively-ascertained breast cancer cases and 85 age-matched controls, using a nested case-control design. Median age at first mammogram was 51 years (range, 29-77 years), with a median of 4 years between first and second prediagnostic mammogram (range, 1-15 years). Using linear regression with change in percent density as the outcome, we found that in women who did not go on to be diagnosed with breast cancer, change in percent density decreased as time between first and second mammogram increased (ß = -1.62% per year, p = 0.004). However, in women who did go on to be diagnosed with breast cancer, there was no overall change in percent density associated with time between first and second mammogram (ß = 0.29% per year, p = 0.61); the change over time was statistically significantly different between cases versus controls (p <0.009). If replicated in larger cohorts, these results suggest that within-individual changes in mammographic density as measured by percent density may be a useful biomarker of breast cancer risk.

Risk factors for uncommon histologic subtypes of breast cancer using centralized pathology review in the Breast Cancer Family Registry.

Epidemiologic studies of histologic types of breast cancer including mucinous, medullary, and tubular carcinomas have primarily relied on International Classification of Diseases-Oncology (ICD-O) codes assigned by local pathologists to define histology. Using data from the Breast Cancer Family Registry (BCFR), we compared histologic agreement between centralized BCFR pathology review and ICD-O codes available from local tumor registries among 3,260 breast cancer cases. Agreement was low to moderate for less common histologies; for example, only 55 and 26 % of cases classified as mucinous and medullary, respectively, by centralized review were similarly classified using ICD-O coding. We then evaluated risk factors for each histologic subtype by comparing each histologic case group defined by centralized review with a common set of 2,997 population-based controls using polytomous logistic regression. Parity [odds ratio (OR) = 0.4, 95 % confidence interval (95 % CI): 0.2-0.9, for parous vs. nulliparous], age at menarche (OR = 0.5, 95 % CI: 0.3-0.9, for age ≥13 vs. ≤11), and use of oral contraceptives (OCs) (OR = 0.5, 95 % CI: 0.2-0.8, OC use >5 years vs. never) were associated with mucinous carcinoma (N = 92 cases). Body mass index (BMI) (OR = 1.05, 95 % CI: 1.0-1.1, per unit of BMI) and high parity (OR = 2.6, 95 % CI: 1.1-6.0 for ≥3 live births vs. nulliparous) were associated with medullary carcinoma (N = 90 cases). We did not find any associations between breast cancer risk factors and tubular carcinoma (N = 86 cases). Relative risk estimates from analyses using ICD-O classifications of histology, rather than centralized review, resulted in attenuated, and/or more imprecise, associations. These findings suggest risk factor heterogeneity across breast cancer tumor histologies, and demonstrate the value of centralized pathology review for classifying rarer tumor types.