Localized fibroglandular tissue as a predictor of future tumor location within the breast

Mammographic density (MD) is a strong marker of breast cancer risk, but it is unclear whether tumors arise specifically within dense tissue.

In 231 British women diagnosed with breast cancer after at least one negative annual screening during a mammographic screening trial, we assessed whether tumor location was related to localized MD 5 years prior to diagnosis. Radiologists identified tumor locations on digitised films. We used a validated algorithm to align serial images from the same woman to locate the corresponding point on the prediagnostic film. A virtual 1 cm square grid was overlaid on prediagnostic films and MD calculated for each square within a woman's breast (mean = 271 squares/film). Conditional logistic regression, matching on a woman's breast, was used to estimate the odds of a tumor arising in a square in relation to its prediagnostic square-specific MD.

Median (interquartile range) prediagnostic MD was 98.2% (46.8%-100%) in 1 cm-squares that subsequently contained the tumor and 41.0% (31.5%-53.9%) for the whole breast. The odds of a tumor arising in a 1 cm-square were, respectively, 6.1 (95% CI: 1.9-20.1), 16.6 (5.2-53.2), and 25.5-fold (8.1-80.3) higher for squares in the second, third, and fourth quartiles of prediagnostic MD relative to those in the lowest quartile within that breast (P(trend) < 0.001). The corresponding odds ratios were 2.3 (1.3-4.0), 3.9 (2.3-6.4), and 4.6 (2.8-7.6) if a 3 cm-square grid was used.

Tumors arise predominantly within the radiodense breast tissue.

Localized MD may be used as a predictor of subsequent tumor location within the breast.