Lynch Syndrome - is breast cancer a feature?

Background The debate on whether or not breast cancer is in the tumor spectrum for Lynch syndrome produces a conundrum for healthcare providers. The classic tumor spectrum for Lynch Syndrome (LS) includes colon, endometrial, ovarian, stomach, small intestine, hepatobiliary, urinary tract and brain/central nervous system cancers. Muir-Torre Syndrome (MTS) is a variant of LS that is associated with additional skin lesions including sebaceous gland tumors and keratoacanthomas. MTS was observed in 28% of LS families when assessing for MTS skin lesions [1]. It has also been reported that 10-14% of individuals with MTS present initially with breast cancer [2,3]. An extensive study published in 2002 excluded breast cancer as part of the tumor spectrum associated with LS [4]. However, more recently it was reported that DNA mismatch repair (MMR) gene deficiencies were identified in 51% of breast cancers arising in MMR mutation carriers [5]. Another study reported a male with an MLH1 mutation who had both colon and breast cancer. The breast cancer exhibited somatic reduction to homozygosity for the MLH1 mutation [6]. Here we report two unrelated families in which the proband has a germline MMR gene mutation and bilateral breast cancer, and one family in which the proband had ovarian and renal cancer and her daughter, maternal aunt and cousin had breast cancer at age 47, 59, and 48 respectively. This raises the question are these breast cancers associated with the MMR mutations or a breast cancer susceptibility gene and what testing should be offered?