Genetic Implications of Breast Cancer Flashcards Preview

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Flashcards in Genetic Implications of Breast Cancer Deck (21)
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1
Q
What's the lifetime risk for breast cancer for a woman in the US?
A
13%
2
Q
5 causes of hereditary breast cancer?
A
BRCA1
BRCA2
TP53
PTEN
Undiscovered genes
3
Q
What process to BRCA1 and BRCA2 gene products play a role in?
A
Homologous DNA repair.
4
Q
What makes a DNA test for breast cancer related genes useful?
A
Defined response to positive result.
Defined response to negative result.
5
Q
What is absolute risk of breast cancer in carriers of BRCA1/BRCA2 mutations?
A
60-80% risk (vs. 13% in general population)
6
Q
Does BRCA1 mutation increase the risk of breast cancer in men?
A
Yes - but it's going from 0.1% incidence to 1-2% incidence. (look into it if you see breast cancer in a man)
7
Q
Outside of reproductive cancers, what specific cancers to BRCA1 and/or BRCA2 mutations increase the risk of?
A
BRCA1: pancreas
BRCA2: pancreas and melonoma
8
Q
Which BRCA gene increases the risk of prostate cancer in men?
A
BRCA2
9
Q
Diagnosis of breast cancer before what age would make you suspicious of BRCA1/2 mutation?
A
- Before age 40
- At least 2 women in same lineage with breast cancer under 50
- Ashkenazi Jewish woman
- Triple negative breast cancer under 50 (neg ER/PR/HER2-neu)
10
Q
Ethnic group noted as having higher rates of carrying BRCA1/2?
A
Ashkenazi Jews
11
Q
Who is it most informative to test for deleterious mutations?
A
AFFECTED FAMILY MEMBER (person who actually has the disease)
A negative result in an unaffected individual doesn't tell you much about their risk.
12
Q
What are "variants of unknown significance"?
What's one way to figure out their significance?
A
- Mutations in the tested gene, but unclear whether they cause loss of function.
- Test many family members to see if the specific mutation tracks with cancer incidence
- MUCH more common in African American population
13
Q
5 things you do in response to positive BRCA1/2 test?
A
Test adult relatives.
Increase surveillance.
Lifestyle changes.
Chemo-prevention.
Prophylactic surgery.
14
Q
What's the penetrance like in BRCA1/2 mutations?
A
Not 100%.--> there is significant variability in penetrance
May be modified by other genes and environment.
15
Q
Does Risk Reducing Salpingo-Oophrectomy work to prevent cancer and all-cause mortality?
A
Yes.
It has the greatest effect when used as secondary prevention - but this isn't surprising, as these women are higher risk.
16
Q
Do BRCA1/2 related tumors have worse prognoses than sporadic tumors?
A
Nope. There is no difference in prognosis. Some ovarian tumors in BRCA1/2 carriers may actually respond better to chemo/ have better prognosis (with use of platinum chemo agents)
17
Q
Might the specific kind of chemotherapy that is used be more effective when the patient is a BRCA1/2 carrier?
A
Yes.
At least in BRCA1-deficient tumors, cisplatin works better because it's a kind of damage these cells can't repair.
(taxanes don't seem to work as well)
18
Q
What is synthetic lethality? What does it take advantage of?
A
BRCA1/2 normally repairs double-stranded DNA breaks. PARP works in an alternative dsDNA break repair mechanism.
If you inhibit PARP in a BRCA-deficient cell, the repair pathway is knocked out entirely and results in CELL DEATH
19
Q
What nefarious phenomenon has been seen in tumors that become resistant to "synthetic lethality"?
A
Second mutations that restore BRCA proteins function (normally is knocked out in people who carry the BRCA1/2 mutations), allowing them to overcome PARP inhibitors and platinum agents.
20
Q
What have GWAS revealed about heritability of breast cancer?
A
- Dominant alleles have been ID'd
- FGFR2 (SNP gene)
- Any1 SNP will raise risk only minimally
- SNP panels may have future application to give overall risk level
21
Q
How are BRCA1 tumors different from BRCA2 tumors? What may this mean for TX?
A
BRCA1= Triple negative (ER/ PR/ HER2-neu)

BRCA2= ER +

May not have the same sensitivity to the same drugs