Hereditary Breast Cancer Flashcards
somatic vs germline mutations–> which one can cause “cancer family syndrome”
Somatic Mutations: occur in non germline tissue, are non heritable and are acquired by alterations. Common for all cancers.
Germline Mutations: present in the sperm and egg which are heritable. Cause cancer family syndrome.
Sporadic Cancer– the Knudson Two Hit Model
We require two hits to DNA or to genes to cause cancer within the cell. In a normal sporadic scenario, if you have two copies of tumor suppressor genes, your cell is happy and acting appropriately. By chance, if you acquire a mutation in one of those copies, you only have one tumor suppressor gene. That’s fine, but if you get a second hit over time within the cell to knock out the other tumor suppressor genes , you now have a cell that cannot regulate its cell cycle anymore.
Inherited Cancer: you’re born with that first hit present in all of the cells in your body. You’re essentially one step closer
Hereditary Cancer Syndromes
>100 unique cancer predisposition syndrome
Caused by mutations in _ __ __ or genes involved in DNA __ pathways
Hereditary __ and __ cancer syndromes are most common (HBOC, lynch syndrome)
Others: melanoma, endocrine tumors, kidney cancer, childhood cancer symptoms,
Most are autosomal dominant (with incomplete penetrance)
Hereditary Cancer Syndromes
>100 unique cancer predisposition syndrome
Caused by mutations in tumor suppressor genes or genes involved in DNA repair pathways
Hereditary breast and colon cancer syndromes are most common (HBOC, lynch syndrome)
Others: melanoma, endocrine tumors, kidney cancer, childhood cancer symptoms,
Most are autosomal dominant (with incomplete penetrance)
features of hereditary cancer
- Multiple tumors in the same organ (bilateral breast cancer)
- Multiple primary cancer (breast and ovarian cancer)
- Unusually young age at diagnosis
- Unusual presentation of tumour (breast cancer in a male)
- Rare tumours or uncommon histology
- Family History: three generation pedigree, look at both sides of the family, age at diagnosis, primary cancer diagnosis, ethnicity, remember that cancer is common, limitations of family history (small families, limited/inaccurate information, non-paternity)
risk factors for breast cancer
family history
early menarche
being on HRT during menopause
other cancer
smoking/drinking
NOT breastfeeding
dense breasts
radiation therapy
high fat diet, obestiy.
no children that you birthed
list dome high risk breast cancer genes
BRCA1 and BRCA 2
4-5 x incrase risk for BC
Moderate Risk breast cancer genes: 2-4 fold increased risk for breast cancer. __, __, __
Cancer risks and management guidelines are not as well defined as for high risk genes.
Testing criteria for genetic breast cancer testing
- family history
- strange presentation: bilateral BC, male with BC
- triple negative breast cancer
- any epithelial ovarian cancer
BRCA 1 and 2 cause anomalies in __ ___ genes
tumor suppressor genes.
which BRCA gene is more assocaited with ovarian cancer?
BRCA1 carries an estimated 44% risk of ovarian cancer.
outlien the steps of breast cancer surveillance in a high risk breast cancer screening population
Annual screening MRI starting at the age of 25, higher sensitivity than mammogram alone, higher false positive rate.
Annual mammogram starting age 30
Clinical breast exam
+/- regular breast self-exam
T?f there is a screening test for ovarian cancer
false. screening is generally not recommended
3 key ways of BC and OC prevention
Risk Reducing Salpingo-Oophorectomy: recommended after childbearing (35-40yrs), must include the removal of fallopian tubes, reduces ovarian cancer risk by 90-95%, risks/adverse effects (surgical menopause)
Risk Reducing Mastectomy: reduces breast cancer risk by 95%, various options for reconstructive surgery.
PARP Inhibitors: exploit tumor DNA repair pathways deficiencies in BRCA1/2 mutation carriers to preferentially kill cancer cells
Specific PARP inhibitors have been approved by Health Canada for first line and maintenance therapy for recurrent BRCA ½ associated platinum sensitive ovarian cancer and for metastatic BRCA ½ associated breast cancer
which ethnicities are predisposed to have hgiher rates of BRCA rates in ppopulation?
1/40-1/50 in Ashkenazi Jewish
Founder mutations in other populations (French Canadian, Iceland, Dutch)
