Cancer - the Beginning: Biology, Pathology and Genetic Predisposition
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1 Cancer - the Beginning: Biology, Pathology and Genetic Predisposition Disclosure I have no conflicts of interest in relation to this program or presentation. Ashley V Daley, MS, CGC Genetic Counselor Virginia Piper Cancer Institute Allina Health October 11, 2018 Objectives Define cancer and identify general terminology Summarize cancer causes and review how cancer occurs Recognize hereditary cancer syndromes and patients who should consider hereditary cancer genetic testing Cancer: A History B.C.: Edwin Smith Papyrus - "do thou nothing there against ~420 B.C.: Hippocrates is credited with naming cancer (carcinoma) karkinoma is Greek for crab Cancer: A Definition According to the American Cancer Society A group of diseases characterized by uncontrolled growth and spread of abnormal cells. If the spread is not controlled, it can result in death. Similarities: Abnormal, Uncontrollable, Invasive Differences: Cell of origin Not a single condition, but actually 100s of different diseases Cancer types (NCI) Lifetime Risk of Developing Cancer: Approximately 38.4 percent of men and women will be diagnosed with cancer of any site at some point during their lifetime, based on data (SEER data) Cancer: Terms Carcinoma: Cancer that begins in the skin or tissues that line/cover internal organs. Neoplasia: (neo = new, plasia = tissue) Abnormal and uncontrolled cell growth. Tumor: An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Benign (not cancer): cells will not invade, but may continue to grow Malignant (cancer): cells will invade or spread to other parts of the body. Invade the basement membrane. In Situ: In its original place (do invade the basement membrane). Example: DCIS in breast NCI AllinaHealthSystems 1
2 Cancer: A Lesson in Cell Biology Cancer: A Lesson in Cell Biology yourgenome.org Cancer: A Lesson in Cell Biology Cancer: A Genetic Disease Cancer: A Genetic Disease AllinaHealthSystems 2
3 Cancer: Risk Factors Cancer: Pathology bioninja Germline Mutations Occur initially in eggs and sperm Are inherited Familial Cancer, Genetic cancer Once inherited, mutation is in all cells of the body ~3-10% of cancer cases Somatic Mutations Occur in non-germline cells (breast, colon, lung, blood cells, etc.) NOT inherited Sporadic cancer ~90-97% of cancer cases Medscape Cancer: Somatic Genetic Testing MGL-counseling aids AllinaHealthSystems 3
4 Sporadic Cancers Hereditary Cancers Cancerous Cell Medscape Cancerous Cell Cancer: When is it Inherited? Cancer: Genetic Counseling Red Flags for Hereditary Cancer Risk YOUNG Breast cancer < age 45; colon cancer < age 50 RARE Examples include Ovarian, Male Breast, Pancreatic MULTIPLE Two or more different cancers in the same person FAMILY Two or more family members with the same or related types of cancer. Breast/Ovarian/Prostate/Pancreatic Colon/Uterine/Ovarian Cancer: Genetic Counseling Educate Basic genetics and inheritance Cancer genetics and risk Discuss Risks, benefits, and limitations of testing Possible genetic test results Management options Psychosocial issues testing other relatives, timing of testing, etc. Cancer: Family History Evaluation Breast 75 Test Logistics AVERAGE GENETIC CONSULT: 1 HOUR 31 Gene Scene AllinaHealthSystems 4
5 Cancer: Family History Evaluation Cancer: Family History Evaluation Breast 70 Breast 40 Skin 59 Bladder 65 Ovarian 55 Pancreatic Breast Breast 30 Suspicious Verify Family History Verbally reported family history Revised family history based on pathology reports Stomach Ca Ovarian Ca, 43 d. 49 Bone Ca d. 59 Prostate Ca Breast Ca, 45 d. 59 BPH dx 54 We know a family is appropriate for testing What are our testing options? Where? Ambry, GeneDx, Invitae, Myriad, Color, etc. What? DNA sequencing and del/dup analysis of specific genes related to inherited cancer syndromes Why? Guide screening and risk management Limitations & Risks Unable to look at every risk gene Possibility of unclear results Unable to screen/prevent all cancer risks Anxiety/distress Insurance discrimination BRCA1 AllinaHealthSystems 5
6 Multi-Gene Panels Genetic tests to look at dozens of genes related to cancer Similar cost and turn around time as gene specific testing Higher risk of uncertain results Potential for surprises Cancer: Genetic Test Results Positive results with limited information Some genes cancer risks not (yet) well known Results that don t fit Worry/anxiety Mutations in unexpected genes Negative results unaffected person mean nothing if there is a significant family history Inconclusive results 50% BRCA1 50% Cancer: Genetic Test Results BRCA1 Associated Cancer Risks 40% to 87% No Mutation (Negative) VUS- Likely Benign Uncertain Significance (VUS) VUS- Likely Pathogenic Pathogenic (Positive) 15% to 40% 30% Medical management based on personal and family history. Uncertain results do not influence recommendations for care. Medical management based on cancer risks linked with gene where mutation found. 12.5% 10% Increased unknown 1.5% 5% 2% <1% unknown unknown <1% Cancer: Breast Cancer Genes Genetic Information Nondiscrimination Act (GINA) MGL-counseling aids GINAhelp.org AllinaHealthSystems 6
7 Genetics and our understanding of mutations is evolving so today s genetic result must always be re-assessed and interpreted based on current information and studies of modifiers, prophylaxis options, and prevention. - Dr. Michael Hall Fox Chase Cancer Center Oncologist Next-Generation Sequencing 38 Genetics in Oncology Nursing Direct to Consumer Tests Who? 23andMe, AncestryDNA, FamilyTreeDNA, etc. What? Tests for a selection of SNPs, including those related to inherited conditions, health risks, drug responses, and inherited traits Why? Can provide information in disease risk and drug responses Limitations Most risks are multifactorial MD not required to be involved Unexpected results (APOE-4, 3-site Jewish BRCA1/2) Overly reassured by results (3-site Jewish BRCA1/2) Ambry Genetics Important Points Genetic testing for hereditary causes for cancer is a quickly changing and complex field Genetic counselors are here to help! Identifying a hereditary cause for cancer aids with prevention/screening for the patient and family. Be careful to clarify when asking a patient have you had genetic testing? To Contact Me Ashley.Daley@allina.com Allina Cancer Genetics: AllinaHealthSystems 7
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