AIMS: In recent years histopathology has made an important contribution to the study of familial breast cancer, largely on the basis of the distinctive cancer phenotype commonly identified in BRCA1-mutation carriers. The aim of this study was to identify this phenotype amongst index cases from families in the kConFab familial breast cancer resource with no known pathogenic mutation ('BRCAX' families). METHODS: The histopathology of breast cancer from 180 individuals was reviewed: 132 members of individual BRCAX families, 26 BRCA1 and 15 BRCA2 mutation carriers and seven mutation negative individuals from families with a known pathogenic mutation. RESULTS: BRCAX breast cancers were a heterogeneous group with 25.8% grade 1, 37.9% grade 2 and 36.4% grade 3. Overall, 45/180 (25%) cases were designated 'BRCA1-phenotype' including 22/132 (16.7%) BRCAX cases, 18/26 (69.2%) BRCA1 and 5/15 (33.3%) BRCA2 mutation carriers. For BRCAX cases, a BRCA1 phenotype designation was negatively correlated with age. CONCLUSIONS: Characteristic breast cancer pathology is not diagnostic of a germline BRCA1 mutation, but it does indicate a pathogenic mechanism that occurs with increased frequency in BRCA1 mutation carriers. In BRCAX families, BRCA1 tumour phenotype may signal the presence of an unidentified BRCA1 mutation. However, this finding must be interpreted with regard to limits of the association between histopathology and genotype, and the importance of clinical context.
AIMS: In recent years histopathology has made an important contribution to the study of familial breast cancer, largely on the basis of the distinctive cancer phenotype commonly identified in BRCA1-mutation carriers. The aim of this study was to identify this phenotype amongst index cases from families in the kConFab familial breast cancer resource with no known pathogenic mutation ('BRCAX' families). METHODS: The histopathology of breast cancer from 180 individuals was reviewed: 132 members of individual BRCAX families, 26 BRCA1 and 15 BRCA2 mutation carriers and seven mutation negative individuals from families with a known pathogenic mutation. RESULTS: BRCAX breast cancers were a heterogeneous group with 25.8% grade 1, 37.9% grade 2 and 36.4% grade 3. Overall, 45/180 (25%) cases were designated 'BRCA1-phenotype' including 22/132 (16.7%) BRCAX cases, 18/26 (69.2%) BRCA1 and 5/15 (33.3%) BRCA2 mutation carriers. For BRCAX cases, a BRCA1 phenotype designation was negatively correlated with age. CONCLUSIONS: Characteristic breast cancer pathology is not diagnostic of a germline BRCA1 mutation, but it does indicate a pathogenic mechanism that occurs with increased frequency in BRCA1 mutation carriers. In BRCAX families, BRCA1 tumour phenotype may signal the presence of an unidentified BRCA1 mutation. However, this finding must be interpreted with regard to limits of the association between histopathology and genotype, and the importance of clinical context.
Authors: Inmaculada de Juan; Sarai Palanca; Asunción Domenech; Lidia Feliubadaló; Ángel Segura; Ana Osorio; Isabel Chirivella; Miguel de la Hoya; Ana Beatriz Sánchez; Mar Infante; Isabel Tena; Orland Díez; Zaida Garcia-Casado; Ana Vega; Àlex Teulé; Alicia Barroso; Pedro Pérez; Mercedes Durán; Estela Carrasco; M José Juan-Fita; Rosa Murria; Marta Llop; Eva Barragan; Ángel Izquierdo; Javier Benítez; Trinidad Caldés; Dolores Salas; Pascual Bolufer Journal: Fam Cancer Date: 2015-12 Impact factor: 2.375
Authors: S Deb; S Q Wong; J Li; H Do; J Weiss; D Byrne; A Chakrabarti; T Bosma; A Fellowes; A Dobrovic; S B Fox Journal: Br J Cancer Date: 2014-12-09 Impact factor: 7.640