Genetics of Breast Disease
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Genetics of Breast Disease
What are the 4 major molecular subtypes of breast cancer?
: (ER+, PR+, HER2-) mostly post menopausal AA women and all non AA woman
: (ER+, PR+, HER2+)
HER2 (ERBB2) amplified
: ER-, PR-, HER2+
Basal or triple negative
: ER-, PR-, HER2- (pre-menopausal AA women)
If a patient is ER+ what med should we give her/him?
tamoxifen or aromatase inhibitor
If a patient is positive for HER2 positive?
Molecular portraits of the molecular subtypes of cancer?
Expression of 21 genes in tumor tissue
Predicts benefit of chemotherapy via prediction of risk of recurrence
Changes plans in 44-57% of those tested (avoidance of chemo)
When a patient is on tamoxifen, why is it so important to get a good medication history?
prozac and paxil can inhibit tamoxifen
What is tamoxifen?
it is a pro drug that is converted to endoxifen by CYP2D6.
What can you keep into account when a patient is on tamoxifen?
asians and AA can have reduced functions while epthiopians can be ultra-rapid tamoxifen
What is the function of the BRCA genes?
part of the ds-DNA homologous repair system
works with damage recognition component and ionizing radiation repair
If there is something wrong with ATM/ATR then
we have ataxia-telangiectasia (auto-recessive)
If there is something wrong with FANCA then
we can have falconi anemia (auto-recessive)
What are the features that indicates BRCA mutations?
multiple cases of early onset breast cancer
breast and ovarian cancer in the same woman
bilateral breast cancer
ashkenazi jewish heritage
male breast cancer
Which is the most common type of BRCA in breast cancer?
BRCA1 it has a higher rate of bc, oc, and 2nd breast cancer. but BRCA2 has an increased risk of prostate cancer
What are the most common type of cancer in BRCA 1 breast tumor?
80% triple negative/basal subtype
What are the common types of ovarian type cancers?
Predominantly papillary serous adenocarcinoma (epithelial)
Primary source is distal fallopian tube
Fallopian tube, ovarian, primary peritoneal
breast, bone, brain blood
Herediatry diffuse gastric cancer
What are other genetic conditions other than BRCA 1 and 2 that are linked with increased breast cancer risk?
Li-Fraumeni syndrome (TP53) – 65-75%
Peutz-Jeghers (STK11) – 50%
Hereditary diffuse gastric cancer (CDH1) – 50%
PALB2-associated cancers – 40%
PTEN hamartoma syndrome (Cowden) – 25-35%
Ataxia-telangiectasia heterozygotes (ATM) – 30-40%
Other homologous repair genes – BARD1, BRIP1, RAD51C, NBN (all 20-30%)
pre-menopausal breast cancer
What is the function of genetic counseling?
Attempts to assist patient in understanding
: Medical facts, Mode of inheritance, Risk of getting breast and/or ovarian cancer (again), Implications for daily life
Options for dealing with the risk
: Breast surveillance, DNA testing, Prophylactic mastectomy and/or oophorectomy, Chemoprevention (tamoxifen, aromatase inhibitor, OCP).
What is the Gail model not good for?
it is not useful for the determination of hereditary cancer risk
What is the clause tables good for?
statistical model to calculate cumulative beast cancer risk based in family history
Tyrer Cusik model
computer based model that are for unaffected women to underdetermine risk if breast cancer and likelihood of hereditary risk
combines gail model, family history, and bayesian analysis
Who do we do genetic testing on?
person affected with cancer that re before 45 or older than 60 if triple negative
person w/o cancer but with family history meeting criteria
any ashkenazi or iscelandic persons
person with a known mutation