JCO Early Release, published online ahead of print Oct 26 2009
Journal of Clinical Oncology, 10.1200/JCO.2008.19.9430
Received September 5, 2008
Accepted July 30, 2009
Contralateral Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
Monika K. Graeser, Christoph Engel, Kerstin Rhiem, Dorothea Gadzicki, Ulrich Bick, Karin Kast, Ursula G. Froster, Bettina Schlehe, Astrid Bechthold, Norbert Arnold, Sabine Preisler-Adams, Carolin Nestle-Kraemling, Mohammad Zaino, Markus Loeffler, Marion Kiechle, Alfons Meindl, Dominic Varga, and Rita K. Schmutzler*
From the Center of Familial Breast and Ovarian Cancer, Department of Gynecology and Obstetrics, University Hospital Cologne, Cologne; Institute of Medical Informatics, Statistics and Epidemiology; and Institute of Human Genetics, University of Leipzig, Leipzig; Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover; Department of Radiology, Charite-Universitätsmedizin, Berlin; Department of Gynecology and Obstetrics, Technical University of Dresden, Dresden; Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg; Abteilung für Medizinische Genetik Wuerzburg, Biozentrum, Wuerzburg; Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Kiel; Institute of Human Genetics, Westfälische Wilhelms-Universität, Münster; Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf; Frauenklinik rechts der Isar der Technischen Universität, München; and Department of Gynecology and Obstetrics, University of Ulm, Ulm, Germany.
* To whom correspondence should be addressed. E-mail: rita.schmutzler{at}uk-koeln.de
Purpose: To estimate the risk for contralateral breast cancer in members of BRCA1- and BRCA2-positive families and to determine predictive risk factors.
Patients and Methods: A retrospective, multicenter, cohort study was performed from 1996 until 2008 and comprised 2,020 women with unilateral breast cancer (index patients, n = 978; relatives, n = 1,42) from 978 families who had a BRCA1 or BRCA2 mutation. Cox regression analysis was applied to assess the association of age at first breast cancer with time from first to contralateral breast cancer, stratified by the affected BRCA gene.
Results: The cumulative risk for contralateral breast cancer 25 years after first breast cancer was 47.4% (95% CI, 38.8% to 56.0%) for patients from families with BRCA1 or BRCA2 mutations. Members of families with BRCA1 mutations had a 1.6-fold (95% CI, 1.2-fold to 2.3-fold) higher risk of contralateral breast cancer than members of families with BRCA2 mutations. Younger age at first breast cancer was associated with a significantly higher risk of contralateral breast cancer in patients with BRCA1 mutation, and a trend was observed in patients with BRCA2 mutation. After 25 years, 62.9% (95% CI, 50.4% to 75.4%) of patients with BRCA1 mutation who were younger than 40 years of age at first breast cancer developed contralateral breast cancer, compared with only 19.6% (95% CI, 5.3% to 33.9%) of those who were older than 50 years of age at first breast cancer.
Conclusion: Contralateral breast cancer risk depends on age at first breast cancer and on the affected BRCA gene, and this risk should be considered in treatment planning.
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