Familial invasive breast cancers: worse outcome related to BRCA1 mutations.
OBJECTIVE
Although all studies confirm that BRCA1 tumors are highly proliferative and poorly differentiated, their outcomes remain controversial. We propose to examine, through a cohort study, the pathologic characteristics, overall survival, local recurrence, and metastasis-free intervals of 40 patients with BRCA1 breast cancer.


METHODS
A cohort of 183 patients with invasive breast cancer, treated at the Institut Curie and presenting with a familial history of breast and/or ovarian cancer, were tested for BRCA1 germ-line mutation. Tumor characteristics and clinical events were extracted from our prospectively registered database.


RESULTS
Forty BRCA1 mutations were found among the 183 patients (22%). Median follow-up was 58 months. BRCA1 tumors were larger in size (P =.03), had a higher rate of grade 3 histoprognostic factors (P =.002), and had a higher frequency of negative estrogen (P =.003) and progesterone receptors (P =.002) compared with non-BRCA1 tumors. Overall survival was poorer for carriers than for noncarriers (5-year rate, 80% v 91%, P =.002). Because a long time interval between cancer diagnosis and genetic counseling artificially increases survival time due to unrecorded deaths, the analysis was limited to the 110 patients whose diagnosis-to-counseling interval was less than 36 months (19 BRCA1 patients and 91 non-BRCA1 patients). The differences between the BRCA1 and non-BRCA1 groups regarding overall survival and metastasis-free interval were dramatically increased (49% v 85% and 18% v 84%, respectively). Multivariate analysis showed that BRCA1 mutation was an independent prognostic factor.


CONCLUSIONS
Our results strongly support that among patients with familial breast cancer, those who have a BRCA1 mutation have a worse outcome than those who do not.
Stoppa-Lyonnet
D
D
Department of Oncology Genetics, Institut Curie, Paris, France. dominique.lyonnet@curie.net
Ansquer
Y
Y
Dreyfus
H
H
Gautier
C
C
Gauthier-Villars
M
M
Bourstyn
E
E
Clough
K B
KB
Magdelénat
H
H
Pouillart
P
P
Vincent-Salomon
A
A
Fourquet
A
A
Asselain
B
B
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015331:Cohort Studies; D018572:Disease-Free Survival; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1 / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D015996:Survival Rate; D016896:Treatment Outcome