Parity and mammographic breast density in relation to breast cancer risk: indication of interaction

We examined whether the harmful influence of nulliparity on breast cancer r isk could be mediated by high mammographic density. Another possibility is that mammographic density and nulliparity act independently or perhaps syne rgistically on breast cancer risk. Our study population consisted of 129 ca ses and 517 controls who had been participants in the Nijmegen breast cance r screening programme for 10 years. Breast density was classified with a fu lly automated technique on digitized mammograms from the screening examinat ion 10 years before diagnosis. Classification was based on the proportion o f the breast that was composed of high density: < 5%, 5-25% or > 25%. Data on parity and potential confounders were obtained using a questionnaire, ad ministered at the same examination. We found that nulliparae with low breas t density (< 5%) were not at increased risk compared to parous women with l ow density: OR 1.1 (95% CI 0.2-5.8). Parous women with < 5% density formed the reference category throughout all analyses, The risks for parous women with 5-25% or > 25% density were 2.7 (95% CI 1.3-5.6) and 3.6 (95% CI 1.7-7 .7) fold increased, respectively. However, when both factors were present ( nulliparity and greater than or equal to 5% density), breast cancer risk wa s 7.1 times higher (95% CI 3.2-15.9). This could indicate that nulliparity and high breast density might work synergistically and that breast density is not just an explanatory factor in the influence of nulliparity on breast cancer risk. It is hypothesized that high breast density (reflecting fibro -glandular tissue with increased epithelial cell proliferation) is more sus ceptible to carcinogenic effects in the undifferentiated epithelial breast tissue of nulliparae than in the differentiated tissue of parous women. Sin ce there were few data, no firm conclusions can be drawn. If these findings can be confirmed in a larger study population, however, they may have impo rtant implications for the prevention and early detection of breast cancer. (C) 2000 Lippincott Williams & Wilkins.