Familial Breast Cancer
Breast cancer is the most common form of cancer affecting women with a lifetime risk of 9-11% predominantly occurring post-menopause. NICE guidelines have been introduced that identify risk of breast cancer according to family history. See Box 1 for risk factors and Box 2 for factors suggestive of inherited disease.
- Mutations in the breast cancer 1 (BRCA1, chromosome 17q) and breast cancer 2 (BRCA2, chromosome 13q) genes cause 2-3% of breast cancer.
- Approximately 10% of women with onset of breast cancer under the age of 40 years have a BRCA1 or 2 gene mutation.
- Inheritance is autosomal dominant.
- Cancer risks with BRCA1:
- Up to 70 years of age, breast cancer 65%, ovarian cancer 39%.
- Cancer risks with BRCA2:
- Up to 70 years of age, breast cancer 45%, ovarian cancer 11%. BRCA2 gene carriers are also particularly at risk of pancreatic, prostate and male breast cancers and malignant melanoma
- Monthly self-breast examination
- According to NICE guidelines, women at increased risk of breast cancer should be offered annual mammography from 40-49 years of age and thereafter once every 3 years.
- Breast MRI screening is also available for those women at very high risk of breast cancer at a young age or known gene mutation carriers, starting at age 30 for BRCA1/2 and age 20 for Li-Fraumeni (TP53) mutations.
- Screening for ovarian cancer in women at increased risk is currently being assessed in a research study, UKFOCCS, which includes pelvic trans-vaginal USS and CA-125 measurements.
Risk factors for breast cancer
- Early menarche & late menopause
- Nulliparity and lack of breastfeeding
- Oral Contraceptive Pill & Hormone Replacement Therapy
- Family history of breast/ ovarian cancer
- Family history of other cancer syndromes eg Peutz-Jeghers syndrome, Li-Fraumeni syndrome, Cowden syndrome, Het-erozygous carriers for ataxia telangiectasia.
Factors suggesting inherited breast cancer
- Autosomal dominant inheritance pattern
- Young age of onset
- Multiple primary tumours in an individual
- Breast, ovarian and prostate cancer occurring on same side of family
- Breast cancer in a male relative
- Oestrogen receptor (ER) negative breast tumour
- Ethnic origin: Ashkenazi Jewish, Icelandic