31st December 2024

Genetics referrals in breast cancer

BRCA1 and BRCA2 gene mutations are germline mutations in tumour suppressor genes, which, if inherited, confer a higher lifetime risk of developing breast cancer. BRCA1 also confers a relatively high risk of ovarian cancer, whilst male carriers of BRCA2 and, to a lesser extent, BRCA1 are at an increased risk of male breast cancer and prostate cancer. Ashkenazi Jewish ancestry is a risk factor for BRCA mutation carriage.

Genetic syndromes that predispose to breast cancer include Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC), which is most associated with colorectal (and endometrial) cancers, and Li-Fraumeni syndrome (TP53 mutation), which also causes sarcoma, brain cancer and leukaemia.

NICE guidelines outline the criteria for specialist genetics referral, which include the following:

• Family history of breast cancer at a young age (e.g. 2 first-degree or 1 first-degree and 1 second-degree relative aged <50)
• Family history of bilateral breast cancer (e.g. at least 1 first-degree relative aged <50)
• Family history of ovarian cancer in combination with a family history of breast cancer at a young age
• Family history of male breast cancer in combination with a family history of breast cancer at a young age

Furthermore, genetics referral should also be considered if there is a family history of sarcoma at a young age (<45), strong paternal family history of breast cancer or childhood glioma.

Those identified to be at an increased lifetime risk of breast cancer may be offered annual surveillance ± prophylactic mastectomy ± oophorectomy ± preventative use of hormone therapy.