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Open Access Highly Accessed Research article

Risk of breast cancer in Lynch syndrome: a systematic review

Aung Ko Win1*, Noralane M Lindor2 and Mark A Jenkins1

Author Affiliations

1 Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Melbourne School of Population and Global Health, The University of Melbourne, 207 Bouverie Street, Parkville, VIC 3010 Australia

2 Department of Health Science Research, Mayo Clinic Arizona, 13400 E. Shea Blvd., Scottsdale, AZ 85259 USA

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Breast Cancer Research 2013, 15:R27  doi:10.1186/bcr3405

Published: 19 March 2013

Abstract

Introduction

Lynch syndrome is an autosomal dominantly inherited disorder of cancer susceptibility caused by germline mutations in the DNA mismatch repair (MMR) genes. Mutation carriers have a substantial burden of increased risks of cancers of the colon, rectum, endometrium and several other organs which generally occur at younger ages than for the general population. The issue of whether breast cancer risk is increased for MMR gene mutation carriers has been debated with evidence for and against this association.

Methods

Using the PUBMED, we identified all relevant studies of breast cancer associated with Lynch syndrome that were published by 15 December 2012. In the review, we included: (i) molecular studies that reported microsatellite instability and/or immunohistochemistry in breast cancer tumors of MMR gene mutation carriers; and (ii) risk studies that investigated risk of breast cancer for confirmed MMR gene mutation carriers or families or clinically and/or pathologically defined Lynch syndrome families.

Results

We identified 15 molecular studies and, when combined, observed 62 of 122 (51%; 95% CI 42 to 60%) breast cancers in MMR gene mutation carriers were MMR-deficient. Of the 21 risk studies identified, 13 did not observe statistical evidence for an association of breast cancer risk with Lynch syndrome while 8 studies found an increased risk of breast cancer ranging from 2- to 18-fold compared with the general population (or non-carriers). There is only one prospective study demonstrating an elevated risk of breast cancer for MMR gene mutation carriers compared with the general population (standardized incidence ratio 3.95; 95% CI 1.59, 8.13).

Conclusions

Since breast cancer is a relatively common disease in the general population, more precise estimates of risk and gene-specific risks will need to utilize large prospective cohort studies with a long follow-up. While current data are inconclusive at a population level, individual tumor testing results suggest that MMR deficiency is involved with breast cancers in some individuals with Lynch syndrome.