title: Novel indications for BRCA1 screening using individual clinical and morphological features.
abstract: Since there is a lack of common family profile among BRCA1-gene carriers, and since the risk of being a mutation carrier is not limited to women with a family history of breast or ovarian cancer, multivariate statistical analysis using the logistic-regression model was carried out, to discriminate between sporadic cases and BRCA1-breast cancers (BRCA1-BCs), especially when information about the family history of breast/ovarian cancer and ethnicity are irrelevant or unavailable, in order to offer specific medical treatment to this population. We examined 32 BRCA1-BCs selected at cancer genetic clinics and 200 consecutive controls without family history of breast cancer for age at onset and current morphological parameters. Following the multivariate analysis, 3 parameters only, namely, early age at cancer onset [odds ratio (OR) for each year = 1.16; p < 0.0001], estrogen-receptor negativity (OR = 5.7; p = 0.01) and poor differentiation (OR = 5; p = 0.03) were found significant factors for predicting BRCA1-carrier status. The expected impact in BRCA1 screening of our model was estimated using data on 5700 breast-cancer cases from a hospital-based registry. Only 50 and 15% of tumours with early age at onset below 35 years present one or the other 2 discriminant parameters respectively. Consequently, whereas the probability of finding a BRCA1 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-group 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, consequently deserves to be tested.
authors.affiliation: Department of Genetic Oncology/INSERM CRI 9703, Paoli-Calmettes Institute, Marseille, France.
authors.forename: F
authors.initials: F
authors.lastname: Eisinger
authors.forename: C
authors.initials: C
authors.lastname: Noguès
authors.forename: J M
authors.initials: JM
authors.lastname: Guinebretière
authors.forename: J P
authors.initials: JP
authors.lastname: Peyrat
authors.forename: V J
authors.initials: VJ
authors.lastname: Bardou
authors.forename: T
authors.initials: T
authors.lastname: Noguchi
authors.forename: P
authors.initials: P
authors.lastname: Vennin
authors.forename: R
authors.initials: R
authors.lastname: Sauvan
authors.forename: R
authors.initials: R
authors.lastname: Lidereau
authors.forename: D
authors.initials: D
authors.lastname: Birnbaum
authors.forename: J
authors.initials: J
authors.lastname: Jacquemier
authors.forename: H
authors.initials: H
authors.lastname: Sobol
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation