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Open Access

Genetic determinants of breast cancer characteristics and outcome in women under 50 years of age

  • MK Schmidt1,
  • A van der Plas1,
  • SR de Kemp1,
  • S Klaver1,
  • B Nota1,
  • B Maertzdorf1,
  • R de Groot1,
  • R Udo1,
  • VTHBM Smit2,
  • A Broeks1,
  • JL Peterse1,
  • FE van Leeuwen1,
  • RAEM Tollenaar2 and
  • LJ van 't Veer1
Breast Cancer Research20057(Suppl 2):P1.07

Published: 17 June 2005


Breast CancerOvarian CancerBreast Cancer PatientBreast Cancer SurvivalBRCA2 Mutation

Germline mutations in BRCA1 and BRCA2 account for approximately 2–3% of breast cancers while CHEK2*1100delC may account for an additional 0.7% [1]. To date, several small studies have suggested a worse outcome of survival in BRCA1 and BRCA2 carriers. However, the evidence is inconsistent and most studies were subject to different types of bias. An increased risk for contralateral breast cancer, especially in interaction with radiotherapy, for CHEK2*1100delC carriers has been shown [2]. Only one study has so far evaluated the impact of CHEK2*1100delC on survival, showing a worse disease-free survival compared with control breast cancer patients [3].

Our aim is to evaluate breast cancer survival and to determine risk estimations for the development of contralateral breast or ovarian cancer (as a second primary), as well as to evaluate tumour characteristics, in BRCA1/2 and CHEK2*1100delC carriers in an unselected, non-family based, retrospective cohort of breast cancer patients diagnosed under age 50. The cohort to be evaluated will include approximately 5000 patients, treated in several Dutch hospitals between 1973 and 1995. Tissue blocks from these patients are being obtained and, after coding, about 70 BRCA1/2 founder and recurrent mutations, representing approximately 72% of the Dutch BRCA1/2 mutations, and the CHEK*1100delC mutation are being determined. Data for 1700 patients from the Netherlands Cancer Institute and the Leiden University Medical Center are being completed. We have so far found, in 1255 samples, 4.1% BRCA1/2 carriers (41 BRCA1 and 11 BRCA2 mutations) and 3.8% CHEK2*1100delC, with no overlap among these groups. An interim analysis showed that BRCA1 tumours seem to have less favourable prognostic characteristics while BRCA carriers have an OR of 3 for contralateral breast cancer compared with the non-BRCA carriers. Genetic determinants of tumour characteristics, risk for contralateral breast cancer and survival of CHEK2*1100delC carriers will be presented.

Authors’ Affiliations

Department of Pathology, Department of Epidemiology and Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Department of Surgery, Department of Pathology and Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands


  1. The CHEK2 Breast Cancer Case–Control Consortium: CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet. 2004, 74: 1175-1182. 10.1086/421251.View ArticlePubMed CentralGoogle Scholar
  2. Broeks A, de Witte L, Nooijen A, Huseinovic A, Klijn JG, van Leeuwen FE, Russell NS, Van 't Veer LJ: Excess risk for contralateral breast cancer in CHEK2*1100delC germline mutation carriers. Breast Cancer Res Treat. 2004, 83: 91-93. 10.1023/B:BREA.0000010697.49896.03.View ArticlePubMedGoogle Scholar
  3. de Bock GH, Schutte M, Krol-Warmerdam EM, Seynaeve C, Blom J, Brekelmans CT, Meijers-Heijboer H, van Asperen CJ, Cornelisse CJ, Devilee P, et al: Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant. J Med Genet. 2004, 41: 731-735. 10.1136/jmg.2004.019737.View ArticlePubMedPubMed CentralGoogle Scholar


© BioMed Central 2005