359 Lynch syndrome and breast cancer: Our experience

Abstract

Introduction and aims: of the study: Lynch Syndrome (LS), also known as Hereditary Non-Polyposis Colorectal cancer (HNPCC), is a hereditary cancer predisposition syndrome caused by autosomal dominant mutation in tumor suppressor genes, the DNA mismatch repair proteins (MMR). Alterations in four DNA MMR genes are related to LS: MLH1, MSH2, MSH6 and PMS2. LS is associated with a variety of cancers, mostly with colorectal and endometrial cancer. We present three cases of breast cancer associated with LS. Methods: Three different patients presented to our clinic with abnormal mammographic findings and were diagnosed with breast cancer and LS. The first patient who was 68 years old and had a personal history of thyroid, endometrial and breast cancer, presented with a newly diagnosed DCIS in the contralateral breast. The second one, a 60 year old woman had a personal history of endometrial cancer, while our third patient was 45 years old and had a family history of breast cancer (sister, 36 years old). Genetic testing revealed mutations in MSH6 gene in the first two patients and in PMS2 gene in the third one. Discussion: Approximately 5% of endometrial and 1% of ovarian cancer occur because of LS. LS patients have a life time risk of 5-14% for breast cancer, 4-12% for ovarian cancer, 30-70% for colon cancer and 30-60% for endometrial cancer. According to the literature breast cancer in LS patients seems to be related more often with MSH6 mutations. Risk management guidelines for these patients are available, recommending earlier and more frequent gastrointestinal and gynecologic screening. Breast cancer screening is based upon the individual risk resulting from personal and family history. In some cases apart from hysterectomy with bilateral salpingo-oophorectomy, bilateral mastectomy appears to be necessary. Conclusions: It is significant to offer genetic consultation and testing in patients with breast cancer and personal or family history of colorectal, ovarian, endometrial and breast cancer.