Mutations at BRCA1: the medullary breast carcinoma revisited.
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.
Eisinger
F
F
Department of Genetic Oncology, Institut National de la Santé et de la Recherche Médicale CRI 9703, Paoli-calmettes Institute, Marseille, France.
Jacquemier
J
J
Charpin
C
C
Stoppa-Lyonnet
D
D
Bressac-de Paillerets
B
B
Peyrat
J P
JP
Longy
M
M
Guinebretière
J M
JM
Sauvan
R
R
Noguchi
T
T
Birnbaum
D
D
Sobol
H
H
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
D019313:BRCA1 Protein