Genetics

Question 1

Genes responsible for breast-ovarian cancer syndrome

and indicated in what percentage of ovarian cancer

Answer 1

BRCA 1 and BRCA 2

15% of ovarian cancer

Question 2

Genes responsible for Lynch syndrome

and indicated in what percentage of ovarian cancer

Answer 2

MLH1
MSH2
PMS2
MSH6

2% of ovarian cancer

Question 3

What are risk reducing strategies

Answer 3

oral contraceptives (protective against ovarian cancer but additional breast cancer risk - reserved for those not wanting RRSO)

risk-reducing surgery

Question 4

What is your life time risk of ovarian cancer with BRCA 1

Answer 4

30-40%

Question 5

What is your life time risk of ovarian cancer with BRCA 2

Answer 5

15-25%

Question 6

What is your annual risk of ovarian cancer if BRCA1 positive and over the age of 40?

Answer 6

Around 1%

Question 7

Requirements for a RRSO (risk reducing salpingo-oophorectomy)

risk of occult malignancy

Answer 7

At least 2/3 of the tube removed and serial sectioning performed at histology

2-10%

Question 8

What should all women with ovarian cancer be tested for?

to guide use of what therapies?

Answer 8

BRCA mutations
Homologous recombination deficiency testing

PARP inhibitors

Question 9

When is bilateral RRSO most effective on risk of ovarian cancer and for how long?

Also useful for risk reduction for breast cancer with which mutation?

Answer 9

Before the age of 40 and for up to 15 years

Breast cancer risk reduction with RRSO for BRCA2

Question 10

Can you use HRT after RRSO?

Answer 10

HRT is likely to be safe in mutation carriers and does not seem to reduce the breast cancer protection offered by pre-menopausal oophorectomy

Question 11

Risk reduction for BRCA1/2

Answer 11

check if same in UK!

Breast -
Annual breast MRI 25-29
Annual mammogram and MRI 30-75 and onwards individualised
RRSO best for BRCA2
Consider Tamoxifen, Raloxifene or aromatase inhibitor (esp for BRCA 2)
Consider RRM

Ovary -
RRSO (BRCA1 35-40, BRCA 2 40-45)
Consider chemoprevention with oral contraceptive

Question 12

Ovarian cancer genes

Answer 12

BRCA 1
BRCA 2

MLH 1
MSH 2

RAD 5 1 C/D
BRIP 1

Question 13

Endometrial cancer genes

Answer 13

EPCAM
PMS2

MLH 1
MSH 2
MSH 6

PTEN (usually somatic mutations)

Question 14

What is Cowden syndrome

Answer 14

Rare autosomal dominant disease with inherited mutation of PTEN

Hamartomas of the skin, also associated with increased risk of breast, thyroid and endometrial cancer

Question 15

Lynch Syndrome - risks

inheritance

Answer 15

Autosomal dominant

General lifetime cancer risks:

Colorectal cancer 20% - 80%
Endometrial cancer 15% - 60%
Ovarian cancer 1% - 38%

Stomach cancer 1% - 13%
Hepatobiliary tract cancer  1% - 4%
Urinary tract cancer 1% - 18%
Small bowel cancer  1% - 6%
Pancreatic cancer 1% - 6%
Brain/CNS tumor 1% - 3%

Question 16

Most common presentation of endometrial cancer with Lynch syndrome

Answer 16

Usually stage 1, frequently have lower uterine segment involvement and TILs.

Question 17

Most common presentation of colon cancer with Lynch syndrome

Answer 17

Usually right sided

Question 18

Risk reduction with Lynch syndrome

Answer 18

Check this is the same in the UK!

GI
Colonoscopy every 1-2 years from 20-25 years (or 2-5 years prior to first colorectal cancer FH diagnosis if earlier)
Consider OGD every 3-5 years from 40 if Asian or GH of gastric or duodenal cancer
Aspirin chemoprevention

Gynae
1-2 yearly pipelle biopsy from 30-35 years
urgent review for irregular bleeding
progesterone chemoprevention
risk reducing TLH/BSO after family complete 40+

Urology
Annual urine dip from 30-35