Abstract
9677 Background: Mammographic density (MD) is a known risk factor for breast cancer and demonstrates heritability. Germline BRCA1/2 mutation-carriers are at markedly increased lifetime risk for breast cancer, but providing a personalized risk estimate for breast cancer is problematic. We investigated MD of BRCA1/2 mutation-carriers to determine (1) if it can predict for BRCA1/2 mutation status and (2) if it is an independent risk factor for breast cancer. Methods: Mammograms were collected from a cross section of germline BRCA1/2 mutation-carriers both affected (Pos Aff) and unaffected (Pos Unaff) by breast cancer and from women negative for a known familial BRCA1/2 mutation (Negs). MD was scored using the Wolfe and Boyd six category classification (SCC) systems and a computer-assisted thresholding algorithm. Odds ratios (ORs) for the effect of MD on the presence of a BRCA1/2 mutation or breast cancer risk were estimated using unconditional logistic regression, using the least dense categories as reference categories for each classification system. ORs were compared using the X2 test for trend with increasing density. Results: In the pilot phase, MD was scored for 34 Pos Aff, 21 Pos Unaff, 33 Negs. For both Wolfe and Boyd SCC systems, a statistically significant difference in density between the Pos Aff and Pos Unaff groups was observed (P=0.034 and 0.043 respectively) with a trend to increased density in the Pos Aff group. No difference in density was observed between mutation-carriers and non-carriers. Mammograms from a further 74 Pos Aff, 117 Pos Unaff and 129 Negs have been located, digitised and scored using all the classification systems and the final analysis will be complete by ASCO 2005. Conclusions: In the pilot phase MD is greater in BRCA1/2 mutation-carriers affected by breast cancer and merits further investigation to investigate potential clinical applications for personalising breast cancer risk estimates and selection of appropriate risk management strategies. MD does not appear to be predictive for BRCA1/2 mutation status suggesting that the reported heritability of mammographic density is associated with genes other than BRCA1/2. No significant financial relationships to disclose.
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