Morphological predictors of BRCA1 germline mutations in young women with breast cancer

Southey MC, Ramus SJ, Dowty JG, Smith LD, Tesoriero AA, Wong EE, Dite GS, Jenkins MA, Byrnes GB, Winship I, Phillips KA, Giles GG, Hopper JL (2011) Morphological predictors of BRCA1 germline mutations in young women with breast cancer. Br J Cancer 104:903-909

BACKGROUND: Knowing a young woman with newly diagnosed breast cancer has a germline BRCA1 mutation informs her clinical management and that of her relatives. We sought an optimal strategy for identifying carriers using family history, breast cancer morphology and hormone receptor status data. METHODS: We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years for whom we conducted extensive germline mutation testing (29 carried a BRCA1 mutation) and a systematic pathology review, and collected three-generational family history and tumour ER and PR status. Predictors of mutation status were identified using multiple logistic regression. Areas under receiver operator characteristic (ROC) curves were estimated using five-fold stratified cross-validation. RESULTS: The probability of being a BRCA1 mutation carrier increased with number of selected histology features even after adjusting for family history and ER and PR status (P<0.0001). from="" the="" most="" parsimonious="" multivariate="" model,="" the="" odds="" ratio="" for="" being="" a="" carrier="" were:="" 9.7="" (95%="" confidence="" interval:="" 2.6-47.0)="" for="" trabecular="" growth="" pattern="" (p="0.001);" 7.8="" (2.7-25.7)="" for="" mitotic="" index="" over="" 50="" mitoses="" per="" 10="" high-powered="" field="" (p="0.0003);" and="" 2.7="" (1.3-5.9)="" for="" each="" first-degree="" relative="" with="" breast="" cancer="" diagnosed="" before="" age="" 60="" years="" (p="0.01).The" area="" under="" the="" roc="" curve="" was="" 0.87="" (0.83-0.90).="" conclusion:="" pathology="" review,="" with="" attention="" to="" a="" few="" specific="" morphological="" features="" of="" invasive="" breast="" cancers,="" can="" identify="" almost="" all="" brca1="" germline="" mutation="" carriers="" among="" women="" with="" early-onset="" breast="" cancer="" without="" taking="" into="" account="" family="">