gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Breast cancer in patients carrying a germ-line CHEK2 mutation: outcome after breast conserving surgery and adjuvant radiotherapy

Meeting Abstract

  • corresponding author presenting/speaker Andreas Meyer - Strahlentherapie und Spezielle Onkologie, Medizinische Hochschule Hannover, Deutschland
  • Thilo Dörk - Geburtshilfe, Pränatalmedizin und Allgemeine Gynäkologie, Medizinische Hochschule Hannover
  • Christof Sohn - Frauenklinik, Universitätsklinikum Heidelberg
  • Johann H Karstens - Strahlentherapie und Spezielle Onkologie, Medizinische Hochschule Hannover
  • Michael Bremer - Strahlentherapie und Spezielle Onkologie, Medizinische Hochschule Hannover

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP005

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dkk2006/06dkk115.shtml

Veröffentlicht: 20. März 2006

© 2006 Meyer et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: Mutations in DNA double strand-break repair genes can confer an increased risk for breast cancer due to overall reduced DNA repair capacity. The CHEK2 gene that encodes a radiation-induced checkpoint kinase, has been identified as a breast cancer susceptibility gene. We here report on the clinical outcome of a hospital-based cohort of early stage breast cancer patients carrying one of three distinct mutations in the CHEK2 gene compared to non-carriers following breast conservative surgery and adjuvant radiotherapy.

Methods: 150 patients with early-stage breast cancer (T1-2) receiving postoperative radiotherapy after breast conserving surgery were included in this analysis 25 patients (carriers) were heterozygous for one of three CHEK2 gene mutations (I157T, n=13; 1100delC, n=10; IVS2+1G>A, n=2), the comparison group consisted of 125 early-stage breast cancer patients (non-carriers) without a CHEK2 gene mutation.

Results: Median follow-up was 87 months. Local recurrences occurred in 11 (carriers, 3; non-carriers, 8) and distant metastases in 27 patients (carriers, 8; non-carriers, 19); 25 patients had deceased (carriers, 8; non-carriers, 17) with all but 3 deaths related to breast cancer. Actuarial 7-year local relapse-free survival was 86 % in carriers vs. 90 % in non-carriers (p = 0,475); actuarial metastasis-free and overall survival at 7 years were 64 % vs. 84 % (p = 0,045) and 69 % vs. 87 % (p = 0,097), respectively. In a multivariate step-wise Cox regression analysis the presence of a CHEK2 mutation remained a borderline statistically significant discriminator for metastasis-free survival (p = 0,048) next to T-stage (p = 0,001). These findings were confirmed when analysing the common CHEK2*I157T variant separately. This missense mutation was associated with worse metastasis-free survival (p = 0,034) in the univariate analysis, that did not remain statistically significant in the multivariate step-wise Cox regression analysis.

Conclusions: Our results indicate that variants in the CHEK2 gene are associated with an increased risk of distant failure in breast cancer patients. The CHEK2 status may represent an adverse prognostic factor. Genetic profiling of functionally relevant polymorphisms in DNA double-strand break repair genes holds considerable promise for assessing individual susceptibility to breast cancer development and outcome.