Reference details
Dite GS, Makalic E, Schmidt DF, Giles GG, Hopper JL, Southey MC (2012) Tumour morphology of early-onset breast cancers predicts breast cancer risk for first-degree relatives: the Australian Breast Cancer Family Registry. Breast Cancer Res 14:R122
ABTRACT
ABSTRACT: INTRODUCTION: We hypothesised that breast cancer risk for relatives of women with early-onset breast cancer could be predicted by tumour morphological features. METHODS: We studied female first-degree relatives of a population-based sample of 452 index cases with a first primary invasive breast cancer diagnosed before the age of 40 years. For the index cases, a standardised tumour morphology review had been conducted for all, estrogen (ER) and progesterone receptor (PR) status was available for 401 (89%), and 77 (17%) had a high-risk mutation in a breast cancer susceptibility gene or methylation of the BRCA1 promoter region in peripheral blood. We calculated standardised incidence ratios (SIR) by comparing the number of mothers and sisters with breast cancer to the number expected based on Australian incidence rates specific for age and year of birth. RESULTS: Using Cox proportional hazards modelling, absence of extensive sclerosis, extensive intraductal carcinoma, absence of acinar and glandular growth patterns, and presence of trabecular and lobular growth patterns were independent predictors with between a 1.8 and 3.1-fold increased risk for relatives (all p < 0.02).="" excluding="" index="" cases="" with="" known="" genetic="" causes="" or="" brca1="" promoter="" methylation,="" absence="" of="" extensive="" sclerosis,="" circumscribed="" growth,="" extensive="" intraductal="" carcinoma="" and="" lobular="" growth="" pattern="" were="" independent="" predictors="" with="" between="" a="" 2.0="" and="" 3.3-fold="" increased="" risk="" for="" relatives="" (all="" p="">< 0.02).="" relatives="" of="" the="" 128="" (34%)="" index="" cases="" with="" none="" of="" these="" four="" features="" were="" at="" population="" risk="" (sir="1.03," 95%="" ci="0.57-1.85)" while="" relatives="" of="" the="" 37="" (10%)="" index="" cases="" with="" two="" or="" more="" features="" were="" at="" high="" risk="" (sir="5.18," 95%="" ci="3.22-8.33)." conclusions:="" this="" wide="" variation="" in="" risks="" for="" relatives="" based="" on="" tumour="" characteristics="" could="" be="" of="" clinical="" value,="" help="" discover="" new="" breast="" cancer="" susceptibility="" genes,="" and="" be="" an="" advance="" on="" the="" current="" clinical="" practice="" of="" using="" er="" and="" pr="" as="" pathology-based="" predictors="" of="" familial="" and="" possibly="" genetic="">
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