Cancer Genetics

Question 1

Characteristics of hereditary cancer families:

Answer 1

• Affected individuals in multiple generations
   Early ages of diagnosis (<50)
   Bilateral cancers (i.e. 2 primary breast cancers, one in each breast)
   Multiple cancers (i.e. 1 individual with 2 different primary cancers [not metastases])

Question 2

Risk for Cancer in BRCA1

Answer 2

Breast 60-85%
Ovarian 44%
Prostate 8-16%

Question 3

Risk for Cancer with BRCA2

Answer 3

Breast 60-85%
Ovarian 27%
Prostate 16%

Question 4

Screening BRCA patients

Answer 4

Breast: 
CBE: every 6 mos. beginning age 25
MRI: annually from age 25
Mammography: annually from age 30
Consider prophylactic mastectomy

Ovarian:
Pelvic exam: annually beginning 18
Transvaginal U/S with color‐Doppler & CA‐125: 2/year
beginning at age 25‐35
Prophylactic BSO w/ or w/o hysterectomy 
1- 35-40
2- 40-45

Question 5

Who should be assessed for BRCA

Answer 5

• Both breast and ovarian cancer
   Ovarian cancer and a close relative with ovarian cancer or premenopausal breast cancer
   Breast cancer at <50 who have a close relative with ovarian cancer or male breast cancer at
  any age
   Ashkenazi Jewish descent with ovarian cancer at any age
   Ashkenazi Jewish descent with breast cancer <40
   A close relative with a BRCA mutation

 Breast cancer <40
 Ovarian, fallopian tube or primary peritoneal cancer of high grade, serous histology at
any age
 Bilateral breast cancer (particularly if the first breast cancer was at <50)
 Breast cancer <50 and a close relative with breast cancer <50
 Ashkenazi Jewish ancestry with breast cancer <50
 Breast cancer at any age and >2 close relatives with breast cancer at any age
 No cancer with a close relative that meets one of the previous criteria

ovarian cancer
Breast <40 
Jewish Breast <50 
3 family members with breast/ovarian/prostate
Early cancer and 1 family member
2 primaries

Question 6

Lynch Syndrome Risk

Answer 6

Colon 18-61%
Endometrial 16-61%
Ovarian 5-10%
Other 
stomach, small bowel, hepatobiliary system, renal pelvis, and ureter

Question 7

Lynch Syndrome Screening

Answer 7

Colonoscopy every 1-2 years at age 20-25 or 2-5 years before the earliest

Endometrial biopsy 1-2 years at age 30-35
ppx TAH/BSO after child bearing

Question 8

When to test for Lynch

Answer 8

Perform tumor testing on all EC or CRC tumor irrespective of age of diagnosis

Pattern of repeated generations of Lynch syndrome‐associated cancers, especially those
diagnosed <60, two or more primaries, and family history

3-cases
2-gen
1 <60