Genetic screening in breast cancer

Recommendations for hereditary breast cancer

  • 1 in 8 to 1 in 12 women develop breast cancer in their lifetime

National Comprehensive Cancer Network guidelines for genetic counseling referral 

  • Patient with personal history of breast cancer
  • Diagnosis < 50 years of age 
  • Triple negative breast cancer diagnosed at <60 years of age
  • Personal history of two breast cancer diagnoses, regardless of age of onset
  • Known mutation in a cancer susceptibility gene within the family
  • Multiple close family members with related cancers (breast, ovarian, colon, endometrial, prostate or pancreatic)
  • Diagnosis of ovarian cancer
  • Diagnosis of breast cancer in men 
  • Ashkenazi Jewish descent with personal history of breast, ovarian or pancreatic cancer 

High-risk genes

  • BRCA1 and BRCA2
  • TP53
  • PTEN
  • CDH1
  • STK11

Moderate-risk genes

  • ATM
  • CHEK2
  • PALB2


  • 6% of breast cancers
  • BRCA1 on Chr 17
  • BRCA2 on Chr 13
  • Avg. age of presentation 40 years (in normal sporadic – 60 yrs)
  • By 70 years: 60% BRCA1 mutation patients develop cancer. 45% BRCA2 develop cancer
  • Mammogram sensitivity drops to 30% (in normal 83%). Dense breast primary reason
  • BRCA1 – higher grade, hormone receptor negative, larger size, poorer prognosis
  • Majority invasive ductal carcinoma. 8% invasive lobular carcinoma 
  • Subset of BRCA1 cancer – medullary type with benign imaging morphology. 19% of BRCA1 cancers 
  • BRCA2 – presents similar to sporadic cancer. Ductal carcinoma-in-situ common. Estrogen receptor positive. Mammogram positive calcification seen in this type. 
  • Male breast cancer – BRCA2 increased lifetime cancer risk. avg. age 60 years (sporadic 67 years)
  • Associated cancers: ovarian, peritoneum, fallopian, pancreas, prostate, colon
  • Ovarian: more common in BRCA1
  • Prostate: BRCA2, aggressive
  • How to screen
    • 25-29: annual breast MRI (mammogram if MRI not available)
    • 30-75: annual mammogram AND MRI
    • For men: annual screening with clinical exam from 35 years. Prostate cancer screening from 45 years for BRCA2
    • 40-50: screening colonoscopy every 3-5 years in BRCA1
    • 50% reduction in breast cancer: if risk reducing salpingo-oophorectomy is done before menopause. Those who don’t want surgery, annual screen, pelvic ultrasound and CA-125 screening from 30-35 years 


  • Associated with Li-Fraumeni syndrome
  • Tumor suppressor gene on Chr 17
  • Li-Fraumeni syndrome: sarcoma diagnosed < 45 years of age with family history of first or second-degree relative with similar sarcoma < 45 years. Soft tissue sarcomas, leukemia, breast, adrenocortical and brain cancers
  • >45 years: lung, prostate, colorectal cancers
  • Breast cancer mean age 34 years; 85% before 60 years
  • IDC and DCIS, HER2 or ER/PR positive 
  • High risk of contralateral breast involvement
  • How to screen
    • 20-29: annual breast MRI
    • 30-75: annual mammogram and MRI
    • Risk reducing bilateral mastectomy recommended
    • Colonoscopy and endoscopy every 5 years starting from 5 years before the age when the cancer came in a relative 
    • Annual dermatology consultation 
  • Mastectomy preferred over lumpectomy to avoid radiation induced increased cancer risk 


  • Cowden syndrome: mucocutaneous hamartomas o skin, breast, brain, thyroid and GIT. Autosomal dominant. 
  • PTEN gene on Chr 10
  • Criteria for Cowden
    • Major: hamartomas, Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma), breast cancer, follicular or papillary thyroid cancer, endometrial cancer, macrocephaly 
    • Minor: subcutaneous lesions (lipoma, fibroma), mental retardation, fibrocystic breast disease, genitourinary tumors. 
  • Breast cancer at 30 years
  • IDC or DCIS common
  • Rare: atypical ductal hyperplasia, lobular carcinoma in situ, fibroadenoma, fibrocystic changes, nipple malformations 
  • How to screen
    • 30-35 years: annual screen with mammogram and MRI 
    • Thyroid screening with ultrasound
    • Endometrial suction biopsy
    • Screening colonoscopy 


  • Hereditary diffuse gastric cancer
  • CDH1 on Chr 16
  • Avg. age 38 years for gastric cancer, 53 years for breast cancer 
  • Invasive lobular carcinoma 
  • How to screen
    • From 30 years: annual MRI and mammography


  • Peutz-Jeghers syndrome: mucocutaneous perioral pigmentation, GIT hamartomatous polyps
  • Autosomal dominant
  • STK11 on Chr 19 
  • Mean age 37 years
  • IDC most common
  • Men: increased risk of Sertoli cell tumors, present with gynecomastia 
  • How to screen
    • 25-29: annual MRI
    • 30 onwards: annual MRI and mammogram 


  • Breast, pancreatic, prostate cancer
  • Ataxia telangiectasia
  • DCIS
  • How to screen
    • From 40 years: annual mammography and MRI 


  • 25% risk of lifetime cancer
  • ER positive 
  • Colorectal, stomach, prostate, kidney, thyroid and sarcomas
  • How to screen
    • From 40 years: annual mammography and MRI


  • Associated with BRCA2
  • 33% risk of breast cancer
  • Pancreatic cancer – solid pseudo papillary epithelial neoplasm 
  • Fanconi anemia 
  • How to screen
    • 30 years and above: annual mammogram and MRI