Male breast cancer in Cowden syndrome patients with germline PTEN mutations

Cowden syndrome (CS) (OMIM 158350) is a multiple hamartoma syndrome associa ted with germline mutations in the PTEN tumour suppressor gene. While CS is characterised most commonly by noncancerous lesions (mucocutaneous trichil emmomas, acral and palmoplantar keratoses, and papillomatous papules), it i s also associated with an increased susceptibility to breast cancer (in fem ales) 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 p atients with classical CS phenotypes and germline PTEN mutations. The first subject was diagnosed with CS indicated primarily by mucocutaneous papillo matosis, facial trichilemmomas, and macrocephaly with frontal bossing at th e age of 31 years. He developed breast cancer at 41 years and subsequently died of the disease. A PTEN mutation, c.902delG, was identified in this sub ject, yet none of his family members showed evidence of a CS phenotype, sug gesting that this PTEN mutation may be a de novo occurrence. The second sub ject had a CS phenotype including multiple trichilemmomas and thyroid adeno ma, developed male breast cancer at 43 years, and died of the disease at 57 years. He was a carrier of a PTEN mutation c.347-351delACAAT that cosegreg ated with the CS phenotype in affected family members. These two cases of m ale breast cancer associated with germline PTEN mutations and the CS phenot ype suggest that CS may be associated with an increased risk of early onset male as well as female breast cancer.