Sept14 M2-Hereditary Breast and Ovarian Cancer Flashcards
real risk of developping breast cancer in a pt with a BRCA1 mutation
+- 65%. depends on RFs (age, FMHx, etc.)
function of BRCA1 and BRCA2 genes that THEY BOTH SHARE
DNA repair
2 cancers with top incidence in men
- prostate
2. colorectal
2 cancers with top mortality in men
- lung
2. colorectal
2 cancers with top incidence in women
- breast
2. lung
2 cancers with top mortality in women
- lung
2. breast
% of women who get breast cancer in their lifetime
10% (bc of cumulative chance as you get very old)
how many women get cancer at age 40
4 out of 1000
most important RFs for breast cancer
- FHx
- age
% of breast cancer due to highly penetrant autosomal dominant genes
3-5%
most common breast cancer gene mutations
BRCA1
BRCA2
genetic testing (BRCA1 and 2 testing) in breast vs ovarian cancer
- breast = only very specific people with a significant risk and FHx
- ovarian: EVERYONE should get genetic testing bc is a more genetic ca
most certain rule as to who should get testing for BRCA1 and BRCA2
all women <80 with HGSC of the ovary, fallopian tube and peritoneum (all pathologies)
most common way of genetic testing done today
testing for big gene panels (screening)
single gene testing is less used now, is more for diagnosis
functions of BRCA1 gene
- DNA repair via homologous recombination
- chromatin remodelling
- transcriptional regulation
- G2-M cell cycle checkpoint control
- ubiquitylation reactions
fcts of BRCA2 gene
- DNA repair via homologous recombination
- cell cleavage and separation at cytokinesis?)
imp concept about BRCA1 mutation
BRCA1 is found in supercomplexes with many proteins.
mutations in any of these prots can cause breast ca
BRCA1 OR BRCA2 mutation: lifetime risk for breast ca
50-80%
BRCA1 mutation: lifetime risk for ovarian ca
42%
BRCA2 mutation: lifetime risk for ovarian ca
18%
period where a person with BRCA1 mutation has the highest risk of getting breast ca
age 35-55
BRCA1 mutation + already had breast cancer: lifetime risk for a 2nd breast ca
80%
BRCA2 mutation + already had breast ca: lifetime risk for a 2nd breast ca
60%
best way to reduce the risk of ovarian ca in a BRCA1 mut carrier (has 42% chance of getting ovarian ca)
remove the fallopian tube and ovaries (lowers risk of HGSC of the pelvis)
main cancer we’re worried about in BRCA1 or 2 mut carriers other than breast and ovarian
peritoneal ca
and others after that would be pancreas, prostate, melanoma
PALB2 mutation: lifetime risk for breast ca
40% (rather than 50-80 with BRCA1 or 2 mut)
primary prevention of breast ca is done how
note done. no medications (tamoxifen not used. only used for secondary prevention, reduces risk of a 2nd one if already had one)
worst to best screening tests for early dx of breast ca
- breast self exam
- ultrasound
- mammography
- MRI (but expensive so used in 25+ with PALB2 mut or in old women with RFs)
surgical options for tx of breast ca
- contralateral preventive mastectomy at time of definitive surgery
- avoids the need for radiotherapy
why is DNA repair in interesting feature of the mutated genes in breast ca
BRCA1 or 2 are mutated so the tumor can’t repair DNA damage
example of breast ca drug using the DNA repair defect of breast tumors with BRCA1 or 2 mut
PARP inhibitors (olaparib)
PARP inhibitors: how do they help as breast ca drugs
- delay progression of the disease
- don’t cure people
- overall survival is the same as with standard regimens
