Family Assessment. Objectives. Comprehensive Family History Important Inexpensive Underutilized genetic tool

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1 Besides the BRCA genes, what else to consider in hereditary breast and ovarian cancer? Laurie M. Connors DNP, APNG, FNP-BC, AGN-BC Objectives Evaluate personal & family history to assess risk for hereditary breast and ovarian cancer syndromes (HBOC) Explore current methods of clinical genetic testing for HBOC Consider the ethical, legal and social implications of clinical cancer genetics & personalized healthcare Family Assessment Comprehensive Family History Important Inexpensive Underutilized genetic tool Maradiegue, A., Edwards, O.T., Seibert, D., Macri, C., & Sitzer, L. (2005). Knowledge, perceptions, and attitudes of advanced practice nursing students regarding medical genetics. Journal of the American Academy of Nurse Practitioners.17(11):

2 Family Health History: The Case for Better Tools Brandon M. Welch, MS, PhD; Willard Dere, MD; & Joshua D. Schiffman, MD Medical University of South Carolina University of Utah JAMA. 2015;313(17): doi: /jama May 5, 2015 HBOC Breast Cancer Most common cancer among U.S. women 2 nd leading cause of ca-related deaths among women Lifetime risk doubles if one 1 st degree relative Ovarian Cancer 3% of cancers among women, but it causes more deaths than any other cancer of the female reproductive system. 5 th leading cause of cancer-related deaths among women ( Breast-ovarian cancer susceptibility genes BRCA1: chromosome 17, cloned in 1994 : chromosome 13, cloned in 1995 Lifetime risk of breast cancer is 45-87% Lifetime risk of ovarian cancer: BRCA1: 40% : 20% 2

3 Testing Criteria for BRCA1/ Decision Making -Right-time Personal history of breast cancer and diagnosed <45 years Diagnosed <50 years with an additional breast primary > 1 close blood relative with breast cancer at any age 1 close blood relative with pancreatic cancer > 1 close blood relative with prostate cancer (Gleason >7) unknown or limited family history Personal history of ovarian cancer Personal history of male breast cancer Describe how women construct the right time to consider risk-reduction surgery. Elapsed time between test disclosure and receipt of surgery ranged from 3 months to 9 years. Need to provide short-term and long-term follow-up contact and information to guide decision making. NCCN Guidelines in Oncology Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version Howard, A.F., Bottorff, J.L., Balneaves, L.G., & Kim-Sing, C. (2010). Women s construction of the right time to consider decisions about risk-reducing mastectomy and risk-reducing oophorectomy. BMC Women s Health, 10 (24), Decisional Conflict Occurs when there is discordance with the presented options and the women s values causing additional stress during a period of transition. Competing alternative options. Multi-Gene Testing Options Patients who are eligible for genetic testing can have all cancer related genes tested for initially Now this can be done upfront along with BRCA testing, with less cost, less time and more answers Next Generation Sequencing sequence multiple genes simultaneously Pierce, P.F. (1993). Deciding on breast cancer treatment: A description of decision behavior. Nursing Research, 42(1), doi: /

4 Li Fraumeni Syndrome Cowden syndrome High risk breast screening Thyroid and colon screening HNPCC/Lynch Syndrome HNPCC/Lynch Syndrome rule 3 relatives with CRC in family 2 or more generations 1 is a first-degree relative of the other 2 1 < 50 years 4

5 Solo provider data from each site with review of the following testing: Syndrome Type of genetic testing BRCA1/2 Community n=195 Results Percent of Positive Negative VUS/ tests other 34% 18% 82% 0% Academic n=57 Results Percent of tests Positive Negative VUS/ other 8% 92% 0% 63% Specific TP53 (6%) (28%) (58%) Syndrome specific genes Next generation sequencing panels : - Breast and ovarian cancer specific High-penetrant genes (cancer-specific panel, with established clinical guidelines) Moderate and high- penetrant genes (cancer-specific panel, some genes lacking established clinical guidelines Comprehensive cancer risk panel (multiple types of cancer syndromes) Next Generation Sequencing Panels Cancer-specific High-Penetrant genes Cancer-specific High & moderatepenetrant genes Comprehensive BRCA1 16% 10% (1.5%) BRCA1 43% 11% BRCA1 CHEK2 MLH1 MUTYH PTEN 7% 8% 87% (14%) 70% (30%) 61% 3% (0.5%) TP53 19% (8%) ATM BRIP1 CDH1 CHEK2 MSH6 MUTYH NBN PTEN RAD50 RAD51C 31% NF1 16 % 0% 5% 0% 16% 33%* 78% (12%) 100% 55% 22% (3.5%) 0% 44%* Cancer (0.5%) (4%) (2%) (9%) (7%) Risk Panels PALB2 MUTYH SMAD4 MUTYH SDHB *+ & VUS NF1 RAD51C SMAD4 TMEM127 *+ & VUS Ethical, Legal and Social Issues Benefits of Genetic Testing Identifies high-risk individuals Identifies noncarriers in families with known mutation Allows early detection and risk reduction strategies May relieve anxiety Precision Oncology Emerging Model of Cancer Treatment Tumor tissue routinely acquired for molecular diagnostics All actionable mutations assessed Therapy selected based on molecular characteristics Privacy: Disclosure of genetic testing to at-risk family members GINA 5

6 Validated Markers Personalized care Cancer Lung (non-small cell) Colon Melanoma Breast Acute Myeloid Leukemia Molecular Tests Commonly Used EGFR, KRAS, ALK, ROS1 KRAS, BRAF, MSI BRAF, KIT, NRAS ERBB2, BRCA1, FLT3, NPM1, CEBPA If we can understand cancer genetics, we can: Identify who will benefit from high-risk intervention Individualize screening based on mutation status and family history Target therapy specifically to the genetic type of cancer PARP inhibitors in BRCA carriers Avoid radiation in TP53 carriers New Era Era of genetic medicine has begun Will challenge long held models of medical practice Clinical care binary Diagnosis Treatment Lack of prevention Precision Cancer Care in the Genomic Era -Requires genetic information for the most complete risk assessment and identification of best therapies/treatment. 6