Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations.
BACKGROUND
Some features of breast cancer in women with a BRCA1 mutation suggest that hereditary breast cancer has a poor outcome. We conducted a national population-based study of Israeli women to determine the influence, if any, of a BRCA1 or a BRCA2 mutation on the prognosis in breast cancer.


METHODS
We obtained data on all incident cases of invasive breast cancer that were diagnosed from January 1, 1987, to December 31, 1988, and recorded in the Israel National Cancer Registry. We requested a paraffin-embedded tumor block or an unstained slide and the corresponding pathological and clinical records for all such cases. DNA extracted from the tumor specimens was analyzed for the three founder mutations in BRCA1 and BRCA2. For each subject, available pathological and oncologic records were reviewed.


RESULTS
We were able to retrieve a pathological sample from 1794 of 2514 subjects (71%). Among those women, we obtained medical records for 1545 (86%). A BRCA1 or BRCA2 mutation was identified in 10% of the women who were of Ashkenazi Jewish ancestry. The adjusted hazard ratios for death from breast cancer were not significantly different among mutation carriers and noncarriers (hazard ratio among BRCA1 carriers, 0.76; 95% confidence interval [CI], 0.45 to 1.30; P=0.31; hazard ratio among BRCA2 carriers, 1.31; 95% CI, 0.80 to 2.15; P=0.28). Among women who were treated with chemotherapy, the hazard ratio for death among BRCA1 carriers was 0.48 (95% CI, 0.19 to 1.21; P=0.12).


CONCLUSIONS
Breast cancer-specific rates of death among Israeli women are similar for carriers of a BRCA founder mutation and noncarriers.
Rennert
Gad
G
Clalit Health Services, National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel. rennert@tx.technion.ac.il
Bisland-Naggan
Shantih
S
Barnett-Griness
Ofra
O
Bar-Joseph
Naomi
N
Zhang
Shiyu
S
Rennert
Hedy S
HS
Narod
Steven A
SA
D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate
D000970:Antineoplastic Agents