Syndromes associated with breast cancer

The incidence of syndrome associated with breast cancer is very low (less than 1%). The various syndromes associated with breast cancer are:

Li-Fraumeni syndrome:

A large number of sporadic cancers are due to mutation in p53 but when this occurs in germline cells, it results in Li-Fraumeni syndrome. It is characterized by premenopausal breast cancer in combination with childhood soft tissue tumours, brain tumors, leukemia, lymphoma, and adrenocortical carcinoma. The probability that these individuals will develop breast cancer is 60% overall. Germline mutations are mostly seen in the exon 7 of p53 gene.[OMIM]

Germline mutations in another gene, hCHK2, have been implicated in the etiology of one classical and two variant Li-Fraumeni families [54].
A detailed account of p53 is discussed here

Cowden syndrome:

It is an autosomal dominant syndrome characterized by hamartomatous lesions in the breast, GI tract (polyps), CNS (Central Nervous System), skin and mucosa, eyes, thyroid, genitourinary tract and bones. Germline mutations in the PTEN gene is responsible for this syndrome. Diagnosis is established through identification of characteristic skin lesions (acral keratosis, facial trichilemmomas, and oral papules). It is also called as multiple hamartoma syndrome.

PTEN is a tumour suppressor gene located on 10q23 chromosome. The gene product of PTEN is a phosphatase which plays an important role in regulating cell growth. Mutation in PTEN gene results in loss of protein function leading to uncontrolled cell proliferation and hamartomatous growths. [55].

Peutz-Jegher syndrome:

Mutation in the STK11 (serine-threonine kinase) gene on chromosome 19 results in this syndrome. It was first described by Dr.Jeghers in 1949. It is an autosomal dominant disorder characterized by hamartomatous polyps in the small bowel and pigmented macules in the buccal mucosa, lips, fingers or toes. Women identified with this syndrome have an increased risk of breast cancer [56].