Genetic screening in breast cancer

Recommendations for hereditary breast cancer

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

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

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