Mammographic Breast Density and Subsequent Risk of Breast Cancer in Postmenopausal Women According to Tumor Characteristics

BACKGROUND: Few studies that investigated the associations between breast density and subsequent breast cancer according to tumor characteristics have produced inconclusive findings. We aimed to determine whether the associations between breast density and subsequent breast cancer varied by tumor characteristics. METHODS: We included 1042 postmenopausal women diagnosed with breast cancer between June 1, 1989, and June 30, 2004, and 1794 matched control subjects from the Nurses' Health Study, an ongoing prospective cohort study of 121 701 registered female nurses across the United States. Breast density was estimated from digitized images using computerized techniques. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires before the date of cancer diagnosis for case subjects and matched control subjects. Polychotomous logistic regression was used to assess associations of breast density with tumor subtypes based on invasiveness, histology, size, grade, receptor status, and involvement of lymph nodes. All tests of statistical significance were two-sided. RESULTS: The risk of breast cancer increased progressively with increase in percent breast density (P(trend) 2 cm) compared with smaller (≤2 cm) tumors (P(heterogeneity) .05). CONCLUSIONS: The findings suggest that higher mammographic density is associated with more aggressive tumor characteristics and also with in situ tumors.