Originally published as JCO Early Release 10.1200/JCO.2007.14.3198 on June 30 2008

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Breast Cancer Onset in Twins and Women With Bilateral Disease

Mikael Hartman, Per Hall, Gustaf Edgren, Marie Reilly, Linda Lindstrom, Paul Lichtenstein, Jaakko Kaprio, Axel Skytthe, Julian Peto, Kamila Czene

From the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet; Department of Surgery, South Hospital, Stockholm, Sweden; Department of Public Health, University of Helsinki; Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland; The Danish Twin Registry, University of Southern Denmark, Odense, Denmark; Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London; and the Section of Epidemiology, Institute of Cancer Research, Surrey, United Kingdom

Corresponding author: Mikael Hartman, MD, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 171 77 Stockholm, Sweden; e-mail: Mikael.Hartman{at}ki.se

Purpose Little is known of the onset of breast cancer in high-risk populations. We investigated the risk of breast cancer in twin sisters and in the contralateral breast taking family history into consideration.

Patients and Methods We analyzed a Scandinavian population-based cohort of 2,499 female twin pairs, in which at least one had a diagnosis of breast cancer and estimated the risk of breast cancer in the sister. Using a total of 11 million individuals in Sweden with complete family links, we identified 93,448 women with breast cancer and estimated the risk of a bilateral breast cancer.

Results The incidence of breast cancer in twin sisters of breast cancer patients was 0.64% per year and 0.42% per year in mono- and dizygotic twin sisters, respectively. In comparison, the risk of familial (affected first-degree relative) and nonfamilial bilateral breast cancer was 1.03% per year and 0.68% per year, respectively. Contrary to the risk of unilateral disease, the risk of cancer in the nonaffected twin and the opposite breast was not affected by age or time since first event. The relative risk of familial bilateral cancer was 52% higher (incidence rate ratio [IRR] = 1.52; 95% CI, 1.42 to 1.64) and the relative risk in the dizygotic twin sister was 25% lower (IRR = 0.75; 95% CI, 0.61 to 0.91) compared with the risk of nonfamilial bilateral cancer.

Conclusion The elevated risk of breast cancer in high-risk groups is little affected by age and time since diagnosis. Our findings suggest that susceptible groups of women might have already aggregated genetic prerequisites for breast cancer.

published online ahead of print at www.jco.org on June 30, 2008.

Supported by Swedish Cancer Foundation and US Army, DAMD 17-03-1-1-0771. The Finnish Twin Cohort is supported by the Academy of Finland Center of Excellence in Complex Disease Genetics.

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

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