Sept14 M2-Hereditary Breast and Ovarian Cancer

Question 1

real risk of developping breast cancer in a pt with a BRCA1 mutation

Answer 1

+- 65%. depends on RFs (age, FMHx, etc.)

Question 2

function of BRCA1 and BRCA2 genes that THEY BOTH SHARE

Answer 2

DNA repair

Question 3

2 cancers with top incidence in men

Answer 3

1. prostate

2. colorectal

Question 4

2 cancers with top mortality in men

Answer 4

1. lung

2. colorectal

Question 5

2 cancers with top incidence in women

Answer 5

1. breast

2. lung

Question 6

2 cancers with top mortality in women

Answer 6

1. lung

2. breast

Question 7

% of women who get breast cancer in their lifetime

Answer 7

10% (bc of cumulative chance as you get very old)

Question 8

how many women get cancer at age 40

Answer 8

4 out of 1000

Question 9

most important RFs for breast cancer

Answer 9

• FHx

- age

Question 10

% of breast cancer due to highly penetrant autosomal dominant genes

Answer 10

3-5%

Question 11

most common breast cancer gene mutations

Answer 11

BRCA1

BRCA2

Question 12

genetic testing (BRCA1 and 2 testing) in breast vs ovarian cancer

Answer 12

• breast = only very specific people with a significant risk and FHx
• ovarian: EVERYONE should get genetic testing bc is a more genetic ca

Question 13

most certain rule as to who should get testing for BRCA1 and BRCA2

Answer 13

all women <80 with HGSC of the ovary, fallopian tube and peritoneum (all pathologies)

Question 14

most common way of genetic testing done today

Answer 14

testing for big gene panels (screening)

single gene testing is less used now, is more for diagnosis

Question 15

functions of BRCA1 gene

Answer 15

• DNA repair via homologous recombination
• chromatin remodelling
• transcriptional regulation
• G2-M cell cycle checkpoint control
• ubiquitylation reactions

Question 16

fcts of BRCA2 gene

Answer 16

• DNA repair via homologous recombination

- cell cleavage and separation at cytokinesis?)

Question 17

imp concept about BRCA1 mutation

Answer 17

BRCA1 is found in supercomplexes with many proteins.

mutations in any of these prots can cause breast ca

Question 18

BRCA1 OR BRCA2 mutation: lifetime risk for breast ca

Answer 18

50-80%

Question 19

BRCA1 mutation: lifetime risk for ovarian ca

Answer 19

42%

Question 20

BRCA2 mutation: lifetime risk for ovarian ca

Answer 20

18%

Question 21

period where a person with BRCA1 mutation has the highest risk of getting breast ca

Answer 21

age 35-55

Question 22

BRCA1 mutation + already had breast cancer: lifetime risk for a 2nd breast ca

Answer 22

80%

Question 23

BRCA2 mutation + already had breast ca: lifetime risk for a 2nd breast ca

Answer 23

60%

Question 24

best way to reduce the risk of ovarian ca in a BRCA1 mut carrier (has 42% chance of getting ovarian ca)

Answer 24

remove the fallopian tube and ovaries (lowers risk of HGSC of the pelvis)

Question 25

main cancer we’re worried about in BRCA1 or 2 mut carriers other than breast and ovarian

Answer 25

peritoneal ca

and others after that would be pancreas, prostate, melanoma

Question 26

PALB2 mutation: lifetime risk for breast ca

Answer 26

40% (rather than 50-80 with BRCA1 or 2 mut)

Question 27

primary prevention of breast ca is done how

Answer 27

note done. no medications (tamoxifen not used. only used for secondary prevention, reduces risk of a 2nd one if already had one)

Question 28

worst to best screening tests for early dx of breast ca

Answer 28

• breast self exam
• ultrasound
• mammography
• MRI (but expensive so used in 25+ with PALB2 mut or in old women with RFs)

Question 29

surgical options for tx of breast ca

Answer 29

• contralateral preventive mastectomy at time of definitive surgery
• avoids the need for radiotherapy

Question 30

why is DNA repair in interesting feature of the mutated genes in breast ca

Answer 30

BRCA1 or 2 are mutated so the tumor can’t repair DNA damage

Question 31

example of breast ca drug using the DNA repair defect of breast tumors with BRCA1 or 2 mut

Answer 31

PARP inhibitors (olaparib)

Question 32

PARP inhibitors: how do they help as breast ca drugs

Answer 32

• delay progression of the disease
• don’t cure people
• overall survival is the same as with standard regimens