Novel indications for BRCA1 screening using individual clinical and morphological features

Since there is a lack of common family profile among BRCAI-gene carriers, a nd since the risk of being a mutation carrier is not limited to women with a family history of breast or ovarian cancer, multivariate statistical anal ysis using the logistic-regression model was carried out, to discriminate b etween sporadic cases and BRCAI-breast cancers (BRCAI-BCs), especially when information about the family history of breast/ovarian cancer and ethnicit y are irrelevant or unavailable, in order to offer specific medical treatme nt to this population. We examined 32 BRCAI-BCs selected art cancer genetic clinics and 200 consecutive controls without family history of breast canc er for age at onset and current morphological parameters. Following the mul tivariate analysis, 3 parameters only, namely, early age at cancer onset [o dds ratio (OR) for each year = 1.16; p < 0.0001], estrogen-receptor negativ ity (OR = 5.7; p = 0.01) and poor differentiation (OR = 5; p = 0.03) were f ound significant factors for predicting BRCAI-carrier status. The expected impact in BRCAI screening of our model was estimated using data on 5 700 br east-cancer cases from a hospital-based registry. Only 50 and 15% of tumour s with early age at onset below 35 years present one or the other 2 discrim inant parameters respectively. Consequently, whereas the probability of fin ding a BRCAI mutation is rated low (6.2%) when the sole criterion of early onset up to the age of 35 years is used, based on our model, in the sub-gro up of women with a tumor that is both estrogen-receptor-negative and poorly differentiated the mutation-detection rate is predicted to be above the 10 % chance level recommended by the ASCO guidelines. This sub-group of women, representing about 1% of all breast-cancer cases in Western countries, con sequently deserves to be tested. Int. J. Cancer (Pred. Oncol.) 84:263-267, 1999. (C) 1999 Wiley-Liss, Inc.