title: Mutations at BRCA1: the medullary breast carcinoma revisited.
abstract: BRCA1-associated breast cancers (BRCA1-BCs) frequently harbor a high histoprognostic grade, p53 alterations, and estrogen receptor negativity. Although these parameters predict a poor outlook, the overall survival in BRCA1-BCs is equivalent to or even better than that in sporadic cases. These features are reminiscent of what is observed for breast carcinoma of the medullary type, a high-grade tumor with a particular favorable course. To explore a possible relationship between this phenotype and BRCA1 mutations, we first compared 32 BRCA1-BCs and 200 consecutive cases of breast cancer without familial history for the prevalence of typical medullary breast carcinoma (TMC) using the criteria given by Ridolfi et al. [R. Ridolfi et al, Cancer (Phila.), 40: 1365-1385, 1977]. Second, we searched for BRCA1 mutations in a set of 18 cases of TMC, using denaturing gradient gel electrophoresis and Cleavase fragment length polymorphism scanning. Six of 32 (19%) BRCA1-BCs were of the TMC type, compared to 0 of 200 controls (P < 0.0001). Among the 18 TMCs, 2 BRCA1 nonsense mutations were found. This corresponds to almost 7 times the contribution of BRCA1 mutations in the general population. Two additional missense mutations were identified. Together, these results suggest that, although TMC and BRCA1-BCs are not strictly coincidental, an important connection between the two populations does exist.
authors.affiliation: Department of Genetic Oncology, Institut National de la Santé et de la Recherche Médicale CRI 9703, Paoli-calmettes Institute, Marseille, France.
authors.forename: F
authors.initials: F
authors.lastname: Eisinger
authors.forename: J
authors.initials: J
authors.lastname: Jacquemier
authors.forename: C
authors.initials: C
authors.lastname: Charpin
authors.forename: D
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: B
authors.initials: B
authors.lastname: Bressac-de Paillerets
authors.forename: J P
authors.initials: JP
authors.lastname: Peyrat
authors.forename: M
authors.initials: M
authors.lastname: Longy
authors.forename: J M
authors.initials: JM
authors.lastname: Guinebretière
authors.forename: R
authors.initials: R
authors.lastname: Sauvan
authors.forename: T
authors.initials: T
authors.lastname: Noguchi
authors.forename: D
authors.initials: D
authors.lastname: Birnbaum
authors.forename: H
authors.initials: H
authors.lastname: Sobol
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D009154:Mutation
chemical_list: D019313:BRCA1 Protein