Replication error in human breast cancer: Comparison with clinical variables and family history of cancer

Replication errors (RER) at microsatellite repeats indicate genomic instabi lity in hereditary nonpolyposis colorectal cancer (HNPCC) and in some spora dic cancers. We have studied genomic instability in 313 sporadic breast tum ors and in 106 tumors from BRCA2, 999del5 carriers at 43 genomic loci on 13 chromosomes. RER was observed in 8/419 (1.9%) of the cases at one or more chromosomal loci. The frequencies of type I and type II RER were similar. T he majority of RER+ tumors showed ER+, PgR(+), high S-phase fraction, tumor size >2 cm and LOH at 2p, 2q and 3p. All 8 RER+ tumors were of the ductal histotype. The breast cancer cases with RER are not part of an HNPCC syndro me and a family history of colorectal cancer growth is not detected in rela tives, with the exception of one case. However, four of the RER+ cases are from individuals carrying the BRCA2, 999del5 mutation. We conclude that RER is a rare somatic event during human breast carcinogenesis and may be asso ciated with progression of breast carcinomas.