BRCA – Flashcard
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chance of developing breast cancer at some point how many diagnosed in year? die? where is the highest rate how many survivors
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1 in 8 230,000/40,000 North America 2.8 million
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biggest risk factors
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age and gender
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when are mammograms recommended to begin now?
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50, not 40
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what percentage of women with breast cancer have hereditary disease?
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5-10%
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what's the difference between somatic genetic mutations and germline genetic mutations?
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somatic is a change, after birth in a gene in one or more non-reproductive cells -; can't be passed to offspring germline is a change that was inherited and occurs in every cell in the body -> increased risk for multiple cancers
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what's changing about genetic testing of tumors?
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now they're really looking at what makes a tumor metastatic
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what percentage of cancers are hereditary, familial, sporadic?
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hereditary: 5-10% familial: 15-20% sporadic: 80%
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what does familial mean?
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it's probably hereditary be we don't understand it completely. probably means there is some environmental component
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what risk do highly penetrant genes confer?
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45-85% lifetime risk of breast cancer
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what types of genes are associated with cancer?
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tumor suppressor and oncogenes
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tell me about the oncogenes
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gain of function is hereditary Hirschprungs -> stomach doesn't work properly
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each cell has how many copies of BRCA1 and BRCA2
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2
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what is the most important cancer risk?
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hereditary mutations
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what is the male consequence of BRCA1?
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increased breast cancer risk ; pancreatic cancer not as high a factor as BRCA2
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what is the male consequence of BRCA2?
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5-10% will have breast cancer by age 70 (bigger rise than in women) + higher risk for prostate, pancreatic, bladder, bile duct, melanoma
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what could be the relation between a rare pediatric syndrome and BRCA?
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Fanconi Anemia
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which gene is a Fanconi Anemia gene?
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BRCA2 is key in the Fanconi complex for DNA repair
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what is Fanconi Anemia?
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rare AR disease -increased risk of hematological malignancies, skeletal and developmental abnormalities
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how do children get Fanconi Anemia?
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both parents are carriers for BRCA2 -; child has mutations on both alleles on chromosome 13 there is a 25% chance of inheriting 2 copies if both parents are carriers
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what will a BRCA family pedigree look like? who should you test?
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the closest person with the disease
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what is the overall incidence among all ethnic groups?
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1/500-1/800
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what is the incidence in Ashkenazi Jews?
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1/40 - 2.3% have altered BRCA1 or BRCA2
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what should happen to African-Americans at high risk for breast cancer?
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should be tested for BRCA there's not a lot known about the spectrum of mutations and modifiers of risk in this population
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which patient should you test
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individual in the family who is most informative - the person w/ cancer at the youngest age
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what if the patient has a direct family member with a known familial mutation?
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test that first
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what if the patient is Ashkenazi Jewish?
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test the three founder mutations first. If negative, full sequence or multi gene panel
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what if the patient isn't Ashkenazi Jewish?
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full sequencing/deletion ; duplication testing of BRCA1 and BRCA2 (all patients)
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what is a multi-gene panel and when should you do it?
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includes BRCA and other breast cancer related genes do it depending on clinical history (pt and family)
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why should you test the individual in a family with the disease?
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This is because if a mutation is identified then you can test other family members for that mutation. Hereditary breast cancer is an autosomal dominant condition. Once the mutation is identified in the person affected, then if a family member tests positive, they have the genetic predisposition. However, if that family member tests negative, it is a true negative
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what does a positive result mean?
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deleterious mutation identified or a change in an exon [deletion/duplication testing]
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variant of uncertain significance?
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;5% of the time -many are missense mutations -variant tracking can help -check to see if reported with a deleterious mutation
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negative?
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interpretation differs if mutation is known or not if mutation is known in family = real negative = average risks apply if mutation is unknown in family = uninformative result
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what are the 3 treatments for hereditary breast cancer?
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screening chemoprevention surgery
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what do significantly mutated genes of breast tumors correlate with?
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genomic and clinical features
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is there an antibody against HER-2 protein?
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Yeah!
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what % of cancers are estrogen receptor positive? progesterone receptor positive? what are the chances of responding to chemo if both estrogen and progesterone receptors are present?
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75% 65% 70%
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what does Tamoxifen do?
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inhibits estrogen gene transcription used in estrogen receptor positive cancers
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what risk is associated with moderate penetrance breast cancer genes?
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CHEK2, ATM, NBS1, RAD50, BRIP1, and PALB2 doubling
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DO THE PRACTICE QUESTIONS AT THE END
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