Male breast cancer in Cowden syndrome patients with germlinePTEN mutations
- James D Fackenthala,
- Deborah J Marshb,
- Anne-Louise Richardsonb,
- Shelly A Cummingsa,
- Charis Engc,
- Bruce G Robinsonb,
- Olufunmilayo I Olopadea
- aCenter for Clinical Cancer Genetics, Department of Medicine, University of Chicago Medical Center, Chicago, IL 60637, USA, bKolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, Sydney NSW 2065, and Department of Medicine, University of Sydney, NSW 2006, Australia, cClinical Cancer Genetics and Human Cancer Genetics Program, Comprehensive Cancer Center, and Division of Human Genetics, Department of Internal Medicine, The Ohio State University, 690C Medical Research Facility, 420 West 12th Avenue, Columbus, OH 43201 USA, and CRC Human Cancer Genetics Research Group, University of Cambridge, UK
- Dr Olopade, folopade{at}medicine.bsd.uchicago.edu
- Revised 19 December 2000
- Accepted 4 January 2001
Abstract
Cowden syndrome (CS) (OMIM 158350) is a multiple hamartoma syndrome associated with germline mutations in thePTEN tumour suppressor gene. While CS is characterised most commonly by non-cancerous lesions (mucocutaneous trichilemmomas, acral and palmoplantar keratoses, and papillomatous papules), it is also associated with an increased susceptibility to breast cancer (in females) and thyroid cancer, as well as non-cancerous conditions of the breast and thyroid. Here we report two cases of male breast cancer occurring in patients with classical CS phenotypes and germline PTEN mutations. The first subject was diagnosed with CS indicated primarily by mucocutaneous papillomatosis, facial trichilemmomas, and macrocephaly with frontal bossing at the age of 31 years. He developed breast cancer at 41 years and subsequently died of the disease. A PTENmutation, c.802delG, was identified in this subject, yet none of his family members showed evidence of a CS phenotype, suggesting that thisPTEN mutation may be a de novo occurrence. The second subject had a CS phenotype including multiple trichilemmomas and thyroid adenoma, developed male breast cancer at 43 years, and died of the disease at 57 years. He was a carrier of aPTEN mutation c.347-351delACAAT that cosegregated with the CS phenotype in affected family members. These two cases of male breast cancer associated with germlinePTEN mutations and the CS phenotype suggest that CS may be associated with an increased risk of early onset male as well as female breast cancer.
