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Annals of Oncology Advance Access originally published online on December 1, 2005
Annals of Oncology 2006 17(3):391-400; doi:10.1093/annonc/mdj095
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© 2005 European Society for Medical Oncology

Survival and prognostic factors in BRCA1-associated breast cancer

C. T. M. Brekelmans1,*, C. Seynaeve1, M. Menke-Pluymers2, H. T. Brüggenwirth3, M. M. A. Tilanus-Linthorst2, C. C. M. Bartels2, M. Kriege1, A. N. van Geel2, C. M. G. Crepin1, J. C. Blom1, H. Meijers-Heijboer3 and J. G. M. Klijn1

1 Department of Medical Oncology, 2 Department of Surgical Oncology and 3 Department of Clinical Genetics, Family Cancer Clinic, Erasmus MC – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

* Correspondence to: Dr C. T. M. Brekelmans, Department of Medical Oncology, Erasmus MC – Daniel den Hoed Cancer Center, PO Box 5201, 3008 AE Rotterdam, The Netherlands. Tel: +31-104391633; Fax: +31-104391003; E-mail: c.brekelmans{at}erasmusmc.nl.

Background: Studies comparing survival in BRCA1-associated and sporadic breast cancer (BC) report inconsistent results and frequently concern small sample sizes. Further, the prognostic impact of the classical tumour and treatment factors is unclear in BRCA1-associated BC.

Patients and methods: We selected 223 BC patients diagnosed between 1980 and 2001 within families with a deleterious germline BRCA1-mutation ascertained at the Rotterdam Family Cancer Clinic. To correct for ascertainment bias, the group of index patients undergoing DNA testing more than 2 years after BC diagnosis (n = 53) was separated from the other BRCA1-patients (n = 170). All BRCA1-associated patients were matched in a 1:2 ratio for age and year of diagnosis to sporadic BC patients. We compared the occurrence of ipsi- and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS). By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in BRCA1-associated and sporadic breast cancers.

Results: For the total group of 669 cases, the median follow-up was 5.1 years, the median age at diagnosis 39 years. We confirmed the existence of the typical BRCA1-associated tumour type and the high CBC incidence. No significant differences between BRCA1-associated and sporadic tumours were found with respect to ipsilateral BC recurrence (HRmult 0.7; P = 0.24), DDFS (HRmult 1.2; P = 0.37) or BC-specific survival (HRmult 1.3; P = 0.23). A trend towards a worse survival was found for BRCA1-associated ductal BC (HRmult 1.5, P = 0.07). Prognostic factors for BRCA1-associated BC were age at diagnosis, tumour size and morphology, and nodal status. Further, survival was non-significantly improved by systemic treatment and a bilateral salpingo-oophorectomy. No effect on survival of a contralateral prophylactic mastectomy was seen.

Conclusions: BRCA1-associated BC is characterised by specific tumour characteristics, a high incidence of CBC and a trend towards a worse survival for the ductal tumour type. Our observation that tumour size and nodal status are also prognostic factors for BRCA1-associated BC implies that the strategy to use these factors as a proxy for ultimate mortality, for instance in BC screening programmes or the consideration of (contralateral) preventive mastectomy, appears to be valid in this specific group of patients.

Key words: BRCA1, hereditary, breast cancer, survival, prognostic factors, histopathology


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