Originally published as JCO Early Release 10.1200/JCO.2006.06.3024 on November 28 2006

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Breast Cancer Survival and Tumor Characteristics in Premenopausal Women Carrying the CHEK2*1100delC Germline Mutation

Marjanka K. Schmidt, Rob A.E.M. Tollenaar, Sanne R. de Kemp, Annegien Broeks, Cees J. Cornelisse, Vincent T.H.B.M. Smit, Johannes L. Peterse, Flora E. van Leeuwen, Laura J. Van 't Veer

From the Departments of Epidemiology, Pathology, and Experimental Therapy, the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam; and Departments of Surgery and Pathology, Leiden University Medical Center, the Netherlands

Address reprint requests to Laura Van 't Veer, Department of Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; e-mail: l.vt.veer{at}nki.nl

Purpose: Women carrying a CHEK2*1100delC germline mutation have an increased risk of developing breast cancer. This study aims to determine the proportion of CHEK2*1100delC carriers in a premenopausal breast cancer population, unselected for family history of breast cancer, and to investigate tumor characteristics and disease outcome with sufficient follow-up.

Patients and Methods: We identified a retrospective cohort of 1,479 patients, who received surgery for invasive breast cancer between 1970 and 1994. All patients were diagnosed before age 50. Paraffin-embedded tissue blocks were collected for DNA isolation (normal tissue), subsequent CHEK2*1100delC analysis, and tumor revision. Median follow-up was 10.1 years.

Results: We detected a CHEK2*1100delC germline mutation in 54 patients (3.7%). Tumor characteristics of CHEK2*1100delC carriers did not differ significantly from those of noncarriers. CHEK2*1100delC carriers had a two-fold increased risk (hazard ratio [HR], 2.1; 95% CI, 1.0 to 4.3; P = .049) of developing a second breast cancer and they had worse recurrence-free survival (HR, 1.7; 95% CI, 1.2 to 2.4; P = .006) and worse breast cancer–specific survival (HR, 1.4; 95% CI, 1.0 to 2.1; P = .072) compared with noncarriers. The poorer disease outcome of CHEK2*1100delC carriers could not be explained by the increased risk of second breast cancer.

Conclusion: Our study, which is representative for the premenopausal breast cancer population, reveals approximately 4% CHEK2*1100delC carriers have an increased risk of second breast cancer and a worse long-term recurrence-free survival rate. Their identification at time of diagnosis and prolonged intensive follow-up should be considered to optimize clinical management.

published online ahead of print at www.jco.org on November 27, 2006.

Supported by the Dutch Cancer Society and the Dutch National Genomics Initiative.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Related Correspondence

• CHEK2 Mutation and Hereditary Breast Cancer
  Natalia Bogdanova, Sergei Feshchenko, Cezary Cybulski, and Thilo Dörk
  JCO 2007 25: 26 [Full Text]
• CHEK2 Mutation and Hereditary Breast Cancer
  Natalia Bogdanova, Sergei Feshchenko, Cezary Cybulski, and Thilo Dörk
  JCO 2007 25: 26 [Full Text]

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