Hereditary Cancer Risk Assessment: Indicators of Hereditary and Familial Risk
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1 Hereditary Cancer Risk Assessment: Indicators of Hereditary and Familial Risk Karen Copeland Certified Genetic Counselor Director International Medical Affairs Myriad Genetics GmbH
2 Impact of Hereditary Cancer
3 Breast and Ovarian Cancer in Switzerland Breast Cancer Incidence: ~5,400 / year 1,300 deaths per year Ovarian Cancer Incidence: ~580 / year 420 deaths per year BRCA1/BRCA2 mutations responsible for 5-10% of breast cancers ~400 breast cancers due to BRCA mutations every year BRCA1/BRCA2 mutations responsible for 12-14% of ovarian cancers ~60 ovarian cancers due to BRCA mutations every year Bundesamt für Statistik Coughlin. AM J Prev Med. 1999;16(2): Narod. Nat Rev Cancer. 2004;4(9): Antoniou. Genet Epidemiol. 2000;18: Anglian. Br J Cancer. 2000;83:
4 Introduction Physicians should view hereditary cancer risk assessment as crucial component of evaluation of new cancer patients Physicians should view the results of genetic testing for hereditary cancer crucial for treatment and managment decisions for appropriate patients 4
5 Key Features of Hereditary Breast / Ovarian Cancer Syndrome Prevalence 1 in in 500 Primarily due to BRCA1/BRCA2 gene mutations Cancer Risks Significant lifetime risks for breast and ovarian cancer Early onset breast cancer Increased risk for other cancers Highly Penetrant Variable expression of age onset, tumor site and number of primary tumors Cancer risk depends on numerous variables, including age and gender Hereditary risk for family members
6 Indicators for Hereditary Breast and Ovarian Cancer Syndrome Age at Diagnosis - Breast Cancer diagnosed < 50y Pathology - Triple negative breast cancer Personal History - Ovarian cancer - Male breast cancer - Two primary breast cancers - Ashkenazi Jewish ancestry with an HBOC-associated cancer*^ - Breast cancer with 2 or more relatives with an HBOC-associated cancer at any age*^ Family History - A previously identified HBOC mutation in the family - Breast Cancer diagnosed < 50y - Ovarian Cancer - Male breast cancer - Two primary breast cancers - Ashkenazi Jewish ancestry with an HBOC-associated cancer*^ - Three or more HBOC-associated cancer at any age*^ *In the same individual and/or on the same side of the family ^HBOC-associated cancers include breast (including DCIS), ovarian, pancreatic, and aggressive prostate cancer (Gleason score of 7) Assessment criteria based on medical society guidelines. For these individual medical society guidelines, go to
7 Case #1 50 year-old woman with Stage 1 ER-negative unilateral invasive breast cancer No family history of breast or ovarian cancer Small maternal family and few female relatives in paternal family history Are there indicators for hereditary cancer? What guidelines does she meet?
8 NCCN Guidelines: Genetic / Familial High-Risk Assessment: Breast and Ovarian Personal history of breast cancer + >1 of following: Dx age <45 Dx any age with >1 close relative with breast cancer <50 or >1 epithelial ovarian cancer at any age 2 breast primaries with 1 st breast cancer dx <50y Dx age <60y with triple negative breast cancer Dx age <50 with a limited family history Dx any age with >2 close relatives with breast cancer at any age Dx any age with >2 close relatives with pancreatic or aggressive prostate cancer at any age Close male relative with breast cancer Ashkenazi Jewish ancestry NCCN.org. Version Published 7 March 2013
9 Guidelines met: Personal diagnosis of breast cancer <50 years with a limited family structure
10
11 Case # 2 58 year-old woman with Stage 2 triple negative unilateral invasive breast cancer diagnosed at age 52 years Lumpectomy with adjuvant chemotherapy Father with prostate cancer (Gleason 8) at age 63 years Paternal grandfather with pancreatic cancer at age 79 Are there indicators for hereditary cancer? What guidelines does she meet?
12 Guidelines met: Triple negative breast cancer <60y Breast cancer diagnosed at any age with >2 close relatives with pancreatic or aggressive prostate cancer at any age
13 NCCN Guidelines: Genetic / Familial High-Risk Assessment: Breast and Ovarian Personal history of breast cancer + >1 of following: Dx age <45 Dx any age with >1 close relative with breast cancer <50 or >1 epithelial ovarian cancer at any age 2 breast primaries with 1 st breast cancer dx <50y Dx age <60y with triple negative breast cancer Dx age <50 with a limited family history Dx any age with >2 close relatives with breast cancer at any age Dx any age with >2 close relatives with pancreatic or aggressive prostate cancer at any age Close male relative with breast cancer Ashkenazi Jewish ancestry NCCN.org. Version Published 7 March 2013
14 Case # 3 55 year-old woman with Stage 2 ER/PR +, HER2 diagnosed with unilateral invasive breast cancer Lumpectomy with adjuvant chemotherapy Paternal aunt with breast cancer at age 49y Are there indicators for hereditary cancer? What guidelines does she meet?
15 Guidelines met: Breast cancer diagnosed at any age with a close relative with breast cancer diagnosed <50 year-old Patient would have been missed if only a first-degree family history was taken
16
17 Case # 4 45-year-old healthy woman Mother diagnosed with ovarian cancer at age 59 years, deceased age 62 Maternal grandmother with breast cancer at age 49 years, deceased age 65 Maternal aunt with breast cancer at 55 years Are there indicators for hereditary cancer? What guidelines does she meet?
18 NCCN Guidelines: Genetic / Familial High-Risk Assessment: Breast and Ovarian Family history only 1 st or 2 nd degree relative meeting any of above criteria 3 rd degree relative with breast or ovarian cancer with >2 relatives with breast cancer (at least 1 <50 y) and/or ovarian cancer Clinical judgment should be used to determine if the patient has a reasonable likelihood of a mutation Testing unaffected individuals considered only when appropriate family member is unavailable for testing Significant limitations of interpreting test results for unaffected individuals should be discussed NCCN.org. Version Published 7 March 2013
19 NCCN Guidelines: Genetic / Familial High-Risk Assessment: Breast and Ovarian Personal history of epithelial ovarian cancer Personal history of male breast cancer Personal history of pancreatic or aggressive prostate cancer at any age with >2 close relatives with breast, ovarian, pancreatic or aggressive prostate cancer at any age NCCN.org. Version Published 7 March 2013
20 NCCN Guidelines: Genetic / Familial High-Risk Assessment: Breast and Ovarian Personal history of breast cancer + >1 of following: Dx age <45 Dx any age with >1 close relative with breast cancer <50 or >1 epithelial ovarian cancer at any age 2 breast primaries with 1 st breast cancer dx <50y Dx age <60y with triple negative breast cancer Dx age <50 with a limited family history Dx any age with >2 close relatives with breast cancer at any age Dx any age with >2 close relatives with pancreatic or aggressive prostate cancer at any age Close male relative with breast cancer Ashkenazi Jewish ancestry NCCN.org. Version Published 7 March 2013
21 Societal Standards and Guidelines ACOG American Congress of Obstetricians and Gynecologists AGA American Gastroenterological Association ASBS American Society of Breast Surgeons ASCO American Society of Clinical Oncologists ASCRS American Society of Colon and rectal Surgeons ESMO - European Society of Medical Oncology NCCN National Comprehensive Cancer Network NICE National Institute of Health Care and Excellence NSGC National Society of Genetic Counselors ONS Oncology Nursing Society SGO Society of Gynecologic Oncologists SSO Society of Surgical Oncology USPSTF U.S. Preventive Services Task Force
22 Genetische Prädisposition Für Brust/Eierstockkrebs Schweizerische Zuweisungsrichtlinien Zur Genetischen Beratung Und Evaluation Eines BRCA1/BRCA2 Gen Tests Diese Richtlinien wurden genehmigt von: Der Schweizerischen Gesellschaft für Medizinische Onkologie Der Schweizerischen Gesellschaft für Medizinische Genetik Der Schweizerischen Gesellschaft für Senologie Der Schweizerischen Gesellschaft für Gynäkologie und Geburtshilfe Dieses erhöhte Risiko basiert auf bestimmten familiengeschichtlichen Mustern einschliesslich: Brustkrebs im jungen Alter Anzahl Brustkrebserkrankungen Eierstockkrebs Beidseitiger Brustkrebs Ethnischer Ursprung: Zurzeit limitiert auf Personen mit Ashkenazi jüdischer Herkunft... ist es sinnvoll Individuen mit der folgenden persönlichen oder familiären Geschichte an Krebserkrankungen für eine genetische Beratung und zur Evaluation einer BRCA1/BRCA2 Gen Testung zuzuweisen:
23 Genetische Prädisposition Für Brust/Eierstockkrebs
24 Identifikationskriterien USZ für ein hereditäres Krebssyndrom
25 Guideline Recommendation for Taking Family History ACOG Committee Opinion, 478 (2011) recommended that all women receive a family history evaluation as a screening tool for inherited risk. Family history information should be reviewed and updated regularly, especially when there are significant changes to family history ASCO Expert Statement, 2014 New guidelines set forth by ASCO recommend clinical oncologists document a detailed cancer family history of first- and second-degree relatives at a new patient s visit including the age of diagnosis Lu K, et al. J Clin Oncol. 2014;10;32(8):
26 Patients in Your Care Appropriate for Hereditary Cancer Testing Breast Cancer Ovarian Cancer Colorectal Cancer Screening Mammography 37% Eisenbraun 100% NCCN 24% Kerber 6% Bellcross Eisenbraun et al. Comm Oncol. 2010;7: NCCNv Genetic/Familial High-Risk Assessment: Breast and Ovarian. Accessed at Kerber RA, et al. Familial Cancer 2005;4: Bellcross CA et al. Genetics in Medicine. 2009;11:
27 Standardization Practice Theory What are the goals? Screen / Evaluate - Accurate personal/family history every patient, annually - Consistent identification - Encompasses both Routine and Survivor Patients Diagnose - Informed Consent - Order test and personalize risk based on the result Treat - Result Disclosure - Surveillance, Surgical, and Chemoprevention options Manage - Customized medicl management plan - Family member impact
28 Moving Forward with Your Hereditary Cancer Protocol Cancer Family History Capture 2 generation minimum with age of diagnosis Increasing Knowledge Training Opportunities: ASCO, ASBS, ESMO Test with a comprehensive genetic panel Utilize test result, guidelines and published data to build short term and long term management plan
29 Differential Diagnosis Other cancers Syndromes Breast Cancer Breast Cancer <35 Li Fraumeni (TP53) Breast Cancer Breast Cancer Breast Cancer Breast Cancer Soft tissue or osteo sarcomas, adrenocorticol, colorectal, brain, leukemia Macrocephaly, endometrial cancer, follicular thyroid cancer, GI hamartomas, mucocutaneous lesions Lobular breast cancer Diffuse gastric cancer Mucocutaneous lesions, GI hamartomas, sex cord tumors, Li Fraumeni (TP53) Cowden syndrome (PTEN) Hereditary Diffuse Gastric Cancer (CDH1) Peutz Jeghers syndrome (STK11) Breast Cancer Ovarian Cancer Breast Cancer Pancreatic Cancer Colorectal cancer Endometrial cancer PALB2 Lynch syndrome (MMR genes)
30 Evaluating Cancer Family History Based on Single Syndromes is Too Narrow
31 Evaluating Cancer Family History Based on Single Syndromes Can Lead to Uncertainty
32 A Negative Result Can Lead to Uncertainty
33 Clinical Rationale for Panel Approach Family history presentations are often complex Phenotype does not always reflect genotype Emerging data demonstrates that the current approach may miss pathogenic mutations
34 Many Genes Contribute to Hereditary Cancer Multiple Genes Can Increase the Risk of a Single Cancer Multiple Cancers Can be Associated with a Single Gene
35 Significant Syndromic Overlap Many patients have personal and family history associated with multiple syndromes 7% of patients appropriate for HBOC testing also meet Lynch criteria 30% of patients appropriate for Lynch testing also meet HBOC criteria Patients that Meet HBOC Syndrome Criteria Patients that Meet Both Criteria Patients that Meet Lynch Syndrome Criteria Saam, J. NCCN Annual Conference poster 2014
36 With Myriad myrisk ~40-50% Relative Increase in Mutation Detection Over Current Approach * BRCA1/2 Lynch Syndrome Tung et al. Presented at ACMG March 2014; Yurgelun et al. Presented at ASCO June 2014; Langer et al. Presented at ASCO June 2014
37 Profile of myrisk Hereditary Cancer Panel A 25-gene panel for the identification of clinically significant mutations impacting inherited risks for eight important cancers.
38 Indicators of Hereditary Cancer An individual with a personal or family history of any one of the following: Abnormal MSI/IHC or histology. Male breast cancer, triple negative breast cancer. **Other Lynch syndrome-associated cancers, 10 or more gastrointestinal adenomatous polyps. HBOC syndrome-associated cancers include breast (including ductal carcinoma in situ [DCIS]), ovarian, pancreatic, and aggressive prostate cancers. ^ Lynch syndrome-associated cancers include colon/rectal, uterine/endometrial, ovarian, stomach/gastric, kidney/urinary tract, biliary tract, small bowel, pancreas, brain, and sebaceous adenoma cancers.
39 Summary Cancer genetics is now a essential element in providing high quality comprehensive care in the gynecologic and oncology practice Every physician and nurse has a role to play in identifying these patients and their families with hereditary cancer risk assessment We can prevent many cancers that were destined to occur
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