Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis

Mammographic features are associated with breast cancer risk, but estimates of the strength of the association vary markedly between studies, and it is uncertain whether the association is modified by other risk factors. We conducted a systematic review and meta-analysis of publications on mammographic patterns in relation to breast cancer risk. Random effects models were used to combine study-specific relative risks. Aggregate data for > 14,000 cases and 226,000 noncases from 42 studies were included. Associations were consistent in studies conducted in the general population but were highly heterogeneous in symptomatic populations. They were much stronger for percentage density than for Wolfe grade or Breast Imaging Reporting and Data System classification and were 20% to 30% stronger in studies of incident than of prevalent cancer. No differences were observed by age/menopausal status at mammography or by ethnicity. For percentage density measured using prediagnostic mammograms, combined relative risks of incident breast cancer in the general population were 1.79 (95% confidence interval, 1.48-2.16), 2.11 (1.70-2.63), 2.92 (2.49-3.42), and 4.64 (3.64-5.91) for categories 5% to 24%, 25% to 49%, 50% to 74%, and > or = 75% relative to < 5%. This association remained strong after excluding cancers diagnosed in the first-year postmammography. This review explains some of the heterogeneity in associations of breast density with breast cancer risk and shows that, in well-conducted studies, this is one of the strongest risk factors for breast cancer. It also refutes the suggestion that the association is an artifact of masking bias or that it is only present in a restricted age range.