The Benefits and Challenges of Genetic Counseling: A Surgical Oncologist Perspective Hank C. Hill, MD Surgical Oncologist St. Vincent’s Surgical Associates Florida Cancer Registrars Association 37 th Annual Conference, Tampa, FL July 27-28, 2015

Disclosures  Speakers Bureau of Myriad Genetics.

Objectives  Understanding the cancer patient and inheritable risks  Recognition of cancer syndromes  Role of primary care provider  Role of oncologist  Genetic testing and challenges  Interpretation of genetic tests and management options (risk-reduction options)

Cancers Associated with Known Genetic Mutations

Inherited Risk for Disease  ACOG Committee Opinion ACOG Committee Opinion No 442, October 2009 Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent (replaces no 298 August 2004)

Inherited Cancer Risk  Here are a few known facts about hereditary cancers.  Hereditary cancers are caused by a change (mutation) in certain genes.  Gene changes may be passed down from either parent to their children.  Increase a person’s risk for developing one or more types of cancer (not everyone who inherits the changed gene will necessarily develop cancer, however).

Inherited Cancer Risk  Most cancers are sporadic and occur in patients without a family history  Spontaneous mutation  Not inherited  Most cancer patients have no clear hereditary component to their cancers.  Approximately 5-10% of all cancers are “inherited” or “hereditary.”

Autosomal Dominance for HBOC Syndrome  Ashkenazi Jewish ancestry  High-grade breast cancer  Aneuploid with basal/ myoepithelial phenotype  P-cadherin positive  EGFR positive  ER negative, PR negative, HER2/ neu negative  Medullary carcinoma of breast (better prognosis)  Serous cystadenocarcinoma  Ovary and fallopian tube  Younger woman  3x risk for prostate

BRCA mutation and cancer risk

Criteria for Genetic Testing  Two or more people, on the same side of the family, have the same type of cancer.  Cancer diagnosed at age 50 or younger.  Cancer in paired organs (e.g. both breasts, both eyes, etc.)  Ethnic risks  Ashkenazi Jewish ancestry

Benefits of Knowing Cancer Risk  Understand the risk of cancer for themselves or their children  Discover if inheritance played a role in the development of their cancer or a family member’s cancer  Review cancer screening tests:  Mammography or colonoscopy, etc.  Make decisions about the use of medical or surgical options to manage their higher cancer risks

Inherited Risk  An inherited risk  Does not mean you have received a diagnosis of cancer.  Born with alterations to your DNA.  Increases your chance of developing certain cancers.

Genetic Counselor  Review personal and family cancer history:  type(s) of cancer  age(s) of diagnosis.  Risks and benefits  Limitation of testing  Emotional implications  Benefits and limitations of testing:  insurance coverage  confidentiality  Genetic testing ???  Personal opinion  Fears  Create an individual plan for screening and management  Modified screening  Review options for risk reduction  Importance for family members

Do patients really want to know if they have a familial hereditary cancer?

Huntsman Cancer Institute Survey Sandra Bugs, MD Medical Director Huntsman Cancer Institute High Risk Cancer Research Program October 2013: 1,202 men and women Age 25-70

Tumor infiltrating lymphocytes MSI-H Tumor infiltrating lymphocytes MSI-H

Breast Cancer Risk Myriad genetics

HNPCC (Lynch) Syndrome Myriad genetics

Familial Melanoma Cancer Myriad genetics

Familial Pancreatic Cancer Schrader K, Offit K, Stadler Zk. Genetic testing for gastrointestinal cancers: A case-based approach. May 15, 2012; Cancer Network

Familial Gastric Cancer Schrader K, Offit K, Stadler Zk. Genetic testing for gastrointestinal cancers: A case-based approach. May 15, 2012; Cancer Network

How Genetic Testing Changes Management for the Healthy Patient with a Positive Family History  Psychological relief if do not have mutation  Lifestyle decisions (childbearing)  Prenatal testing???  When to test children?  Increased surveillance and screening for cancer  Preventive chemotherapy  Biologic therapy.  Holistic therapy for cancer prevention  Consideration of risk reductive surgery  Future:  Dietary  Lifestyle modifications

Impact of Genetic Screening Saving lives with education and appropriate testing Challenges: Infrastructure support Cost Trust in system Legal challenges

Challenges of Genetic Testing and Management of Inheritable Cancer Syndromes

Challenges and Processes  Make tumor screening standard through pathology labs  Use of IHC with mutational analysis (e.g. BRAF) with > 50% reduction in false positive  Increase sensitivity compared with family history criteria  Creation of molecular testing that is equivalent to genetic testing of the tumor to confirm molecular  Creation of tumor screening protocol that may be equivalent to identifying syndrome

Challenges and Processes  Navigation to genetic counseling  Screening positive patients at triage  Screening at postoperative appointment  Dedicated personnel as advocates  Primary care providers, internists  Gynecologists  Gastroenterologists  Oncologists (medical, radiation, surgical)  Geneticists and counselor

Challenges and Processes  IT support for EMR triage to screen family history provided  Decision support  Tracking of family and compliance to screening  Reminder system  Clinician education  Grand rounds and tumor boards  Administration support for “personalized medicine initiatives”  Legal issues over the industry management  “Patent of genes”

Genetic testing is only as good as the counseling that accompanies it BRCA Risk Calculator

Challenges to accept testing from patient’s perspective  Low self esteem  Feeling of guilt  Feels “abnormal”  Feels less than perfect  Lead to non-indicated medical interventions  Potential stigmatization  Discrimination and insurance issues  Employment discrimination

Klimberg VS, Galandiuk S, Singletary ES, et al. Society of Surgical Oncology: Statement on Genetic Testing for Cancer Susceptibility Annals of Surgical Oncology, 6(5): , 1999

Surgical Oncologist  Trust and responsibility  Time  “Adoption” of entire family  Establishing cooperative team  Gastroenterologist, gynecologist, urologist  Dermatologist, medical oncologist  Oncology nurse navigator, primary care provider  Administration and corporate support  Leadership

Surgical Oncologist  Counseling  Medical management  Cancer screening: radiographic, biochemical, endoscopic, clinical criteria.  Prevention, screening, surveillance methods  Prospective clinical research trials  Medical education  Guidelines for testing  CME  Residency education  Patient education  Website, brochures, face-to-face events  Support groups

Surgical Oncologist  Research  Long-term outcome studies  National Advisory Council for Human Genome Research  American Society of Human Genetics  American Society of Clinical Oncology  National Cooperative Registry  Patient-oriented research

Surgical Oncologist  Patient Advocacy  Medical, legal, social, psychological, and ethical issues  Detrimental outcomes of genetic testing:  Genetic discrimination  Differential treatment  Eugenics

Surgical Oncologist  Regulative Legislation:  Strengthen regulatory authority over laboratories  Update laboratories to meet the standard for laboratory genetic services established by American College of Medical Genetics  Prohibit discrimination based on genetic information by insurance companies and employers  Coverage of services  Confidentiality – Genetic privacy  Funding for supportive service

Questions and Discussion  Hank C. Hill, MD  Surgical Oncologist  St. Vincent’s Surgical Associates 