Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome

TY - JOUR

T1 - Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome

AU - Jensen, Uffe Birk

AU - Sunde, Lone

AU - Timshel, Susanne

AU - Halvarsson, Britta

AU - Nissen, Anja

AU - Bernstein, Inge

AU - Nilbert, Mef

AU - Jensen, Uffe Birk

AU - Sunde, Lone

AU - Timshel, Susanne

AU - Halvarsson, Britta

AU - Nissen, Anja

AU - Bernstein, Inge

AU - Nilbert, Mef

N1 - Keywords: Adaptor Proteins, Signal Transducing; Adult; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Colorectal Neoplasms, Hereditary Nonpolyposis; DNA Mismatch Repair; DNA-Binding Proteins; Denmark; Endometrial Neoplasms; Female; Humans; Male; Middle Aged; MutS Homolog 2 Protein; Neoplasms, Multiple Primary; Nuclear Proteins; Ovarian Neoplasms; Pedigree; Urethral Neoplasms

PY - 2010/4

Y1 - 2010/4

N2 - Whether or not breast cancer can be a feature of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome has been debated. In order to clarify if defective mismatch repair (MMR) may indeed play a role in breast cancer, we used the Danish HNPCC register to identify all breast cancers that occurred in MMR gene mutation carriers. In total, 20 female mutation carriers were diagnosed with breast cancer at mean 50 years of age. These tumors were predominantly ductal carcinomas with extensive lymphocytic reactions in 8/14 evaluated tumors. MMR protein immunostaining showed loss of expression of MLHl, MSH2 or MSH6 corresponding to the mutations identified in 7 of the 16 cases investigated, and these tumors were diagnosed at mean 50 (33-66) years of age. The demonstration of defective MMR in a substantial proportion of the breast cancers studied links yet another tumor type to HNPCC. Though the low number do not motivate surveillance, our observation supports a role for defective MMR in breast cancer progression in HNPCC, presumably through accelerated accumulation of mutations in breast cancer-associated genes.

AB - Whether or not breast cancer can be a feature of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome has been debated. In order to clarify if defective mismatch repair (MMR) may indeed play a role in breast cancer, we used the Danish HNPCC register to identify all breast cancers that occurred in MMR gene mutation carriers. In total, 20 female mutation carriers were diagnosed with breast cancer at mean 50 years of age. These tumors were predominantly ductal carcinomas with extensive lymphocytic reactions in 8/14 evaluated tumors. MMR protein immunostaining showed loss of expression of MLHl, MSH2 or MSH6 corresponding to the mutations identified in 7 of the 16 cases investigated, and these tumors were diagnosed at mean 50 (33-66) years of age. The demonstration of defective MMR in a substantial proportion of the breast cancers studied links yet another tumor type to HNPCC. Though the low number do not motivate surveillance, our observation supports a role for defective MMR in breast cancer progression in HNPCC, presumably through accelerated accumulation of mutations in breast cancer-associated genes.

U2 - 10.1007/s10549-009-0449-3

DO - 10.1007/s10549-009-0449-3

M3 - Journal article

C2 - 19575290

SN - 0167-6806

VL - 120

SP - 777

EP - 782

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 3

ER -