A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment

Mark E Robson^*¹, Pierre O Chappuis^*²^,9, Jaya Satagopan³, Nora Wong⁴, Jeff Boyd⁵, John R Goffin⁶^,9, Clifford Hudis¹, David Roberge⁶, Larry Norton¹, Louis R Bégin⁷^,9, Kenneth Offit¹ and William D Foulkes²^,4^,8

¹Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

²Research Institute of McGill University Health Centre, Cancer Prevention Centre, McGill University, Montreal, Quebec, Canada

³Department of Epidemiology/Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

⁴Cancer Prevention Centre, Sir Mortimer B Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada

⁵Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

⁶Department of Oncology, McGill University, Montreal, Quebec, Canada

⁷Department of Pathology, McGill University, Montreal, Quebec, Canada

⁸Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada

⁹Current addresses: Divisions of Oncology and Medical Genetics, University Hospitals of Geneva, Geneva, Switzerland (POC); Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada (LRB); and Division of Hematology/Oncology, Department of Medicine, Tufts University, Tufts University-New England Medical Center, Boston, Massachusetts, USA (JRG)

author email corresponding author email* Contributed equally

Breast Cancer Res 2004, 6:R8-R17doi:10.1186/bcr658


Published:	24 October 2003

See related Commentary: http://breast-cancer-research.com/content/6/1/E7

Abstract

Background

The prognostic significance of germline mutations in BRCA1 and BRCA2 in women with breast cancer remains unclear. A combined analysis was performed to address this uncertainty.

Methods

Two retrospective cohorts of Ashkenazi Jewish women undergoing breast-conserving treatment for invasive cancer between 1980 and 1995 (n = 584) were established. Archived tissue blocks were used as the source of DNA for Ashkenazi Jewish BRCA1/BRCA2 founder mutation analysis. Paraffin-embedded tissue and follow-up information was available for 505 women.

Results

Genotyping was successful in 496 women, of whom 56 (11.3%) were found to carry a BRCA1/BRCA2 founder mutation. After a median follow-up period of 116 months, breast cancer specific survival was worse in women with BRCA1 mutations than in those without (62% at 10 years versus 86%; P < 0.0001), but not in women with the BRCA2 mutation (84% versus 86% at 10 years; P = 0.76). Germline BRCA1 mutations were an independent predictor of breast cancer mortality in multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.2–4.8; P = 0.01). BRCA1 status predicted breast cancer mortality only among women who did not receive chemotherapy (hazard ratio 4.8, 95% confidence interval 2.0–11.7; P = 0.001). The risk for metachronous ipsilateral cancer was not greater in women with germline BRCA1/BRCA2 founder mutations than in those without mutations (P = 0.68).

Conclusion

BRCA1 mutations, but not BRCA2 mutations, are associated with reduced survival in Ashkenazi women undergoing breast-conserving treatment for invasive breast cancer, but the poor prognosis associated with germline BRCA1 mutations is mitigated by adjuvant chemotherapy. The risk for metachronous ipsilateral disease does not appear to be increased for either BRCA1 or BRCA2 mutation carriers, at least up to 10 years of follow up.