Cancer Genetic Counseling Services: What? For Who? How?You can’t help those who are at risk for cancer unless you find them!IT MATTERS FOR THOSE WITH and WITHOUT CANCER

Purpose:• Educate patients about their chance of developing cancers• Help patients obtain personal meaning from cancer genetic

information• Empower patients to make educated, informed decisions about

genetic testing, cancer screening, and cancer prevention

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BE AWARE…..

Familial cancer risk assessment

DOES NOT ALWAYS EQUAL GENE TESTING**

The Goal of Testing is not to test as many people as

possible it is to test the right people

**you can be high risk with a normal gene test

What filled your glass?• Cancer: filled with risk factors

• Density(4-6 vs 1 for HRT) 14/15-BRCA

• Actors

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Why is it Important to Identify Families with Hereditary Cancer Syndromes?( ONLY ~10% of All Cancers)

• High risk for cancer• Multiple organ systems may be involved• Increased risk for second primary cancer• Increased risk of cancer to relatives• Possible treatment(targeted therapy-PARPinhibitors for BRCA;

need for CT, surgery; avoid RT withTP53; ?mTor inhibitors for PTEN,STK11 & immune therapies for Lynch)

• The ultimate goal is treatment or prevention or early detection of cancer- for patient and FAMILY

Not only RX but who to screen & when:

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USPSTF

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HBOC Family History

Breast ca

dx 38

57 60

36 30 32 28 39

Ovarian dx 60d. age 66

Breast ca dx 47

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32 27 3737 36

Cancer

Other “At-Risk” Relatives

Breast ca

dx 38

Cancer

At risk?

57 60

36 30 32 28 39 36

59

32 27 37

Ovarian ca dx 60d. age 66

Breast ca dx 47

Other “At-Risk” Relatives (impacted by genetic testing)

Cancer

At risk

neg+

negneg

57 60

neg

36 30 32 28 39 36+

Breast ca

dx 38

+59

32 27 37

Breast ca dx 47

Ovarian dx 60d. age 66

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NGS Panels - Ovary

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Test w/epithelial ovarian cancer for BRCA! BUTis this enough? AND it’s often FT cancer!!

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Marked Genotypic and Phenotypic Heterogeneity in Hereditary Colorectal Syndromes

Lynch Syndrome Genes

MLH1

PMS2

MSH2 MSH6

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We can help prevent cancer!

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…

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Lynch and Treatment• Neoproteins in LS prompt immune response

• Peds tumors/heme cancers have very few somatic mutations• 50-100/tumor cell with BC/CRC• 100-300 with lung and melanoma- e.g. cancers assoc. with mutagens• BUT 1000s in LS-do mutations encode proteins that are immunogenic?—avg..

1700 mutations per tumor.; tumors are rich in CD8+Tcells; neoproteins may also be source of screen or vaccine

• PD-1 blockage: block inhibition of Tcell response→unleash immune system; • 62% w/LS responded vs 0% controls; 92% had stable disease i.e. control of dis vs 16% in

controls• MSI –H nonCRC 60% responded ; 70% had control; some had primary resistance--? What

if you got loss of function in MCH gene, tumor would be invisible to CD8 cells

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JAMA. 2016;316(1):38-39. doi:10.1001/jama.2016.8291

•Lynch Syndrome Testing:A Missed Opportunity in the Era of Precision Medicine • Boris Pasche, MD, PhD1,2,4; Michael J. Pennison, PhD1,2; Barry DeYoung, MD2,3

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EGAPPmay save more lives than newborn screening

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CANCER There are more than 50 well described cancer susceptibility syndromes,

many of which can result from mutations in more than one gene.(Lindor NM et al., 2008, JNCI)

Many common cancers (e.g. breast, colon, uterine, etc) are tumors related to 10 or more cancer susceptibility genes, making genetic risk assessment essential for cost-effective genetic testing strategies.

(Lindor NM et al., 2008, JNCI)

Surveillance and prophylactic surgery have been shown to reduce cancer-related morbidity and mortality for several cancer susceptibility syndromes.

(Kurian AW et al., 2010, JCO; de Jong AE et al., 2006, Gastroenterology)

Clinical Specialty Area

CANCER Genetic counseling and testing shortly after cancer

diagnosis can help guide patients’ surgical and treatment decisions.

(Weitzel JN et al., 2003, Arch Surg; Schwartz MD et al., 2004, JCO) (Ashworth A, 2008, JCO; Ribic CM et al., 2003, NEJM; Sargent DJ et al., 2010, JCO)

Genetic counselors can help clarify whether a patient who tests negative for breast cancer susceptibility genes (such as BRCA1 and BRCA2) qualifies for breast MRI screening, using risk assessment models and ACS and NCCN breast MRI guidelines.

(Saslow D et al., 2007, CA Cancer J Clin)

Clinical Specialty Area

(continued…)

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Every other lab now says…

The era of hypothesis driven testing may be ending!

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Result Interpretation

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ASCO UPDATES POLICY ON GENETIC & GENOMIC TESTING: JCO2015.63.0996

1. Multi-gene panels:- Providers with expertise in risk assessment should be involved in ordering

and interpreting multi-gene panels that include genes of uncertain clinical utility and genes NOT suggested by the pts personal and/or family hx

- ASCO encourages research to delineate the optimal use of panel –based testing, development of evidence based practice guidelines and educ. of providers on the challenges of using these panels

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1.cont• With new next-gen: greater complexity in pre-test conversation

- Goals? Expectation? Prepare them for numerous possible results:• Positive/helpful results-target for therapy or explanation for hx• Positive surprise results inconsistent with phenotype-does this mean the same-CDH1? LS?• Ambiguous results(VUS)-NOT ACTIONABLE-whether in well described or newly ID’s genes

• NEG=UNINFORMATIVE• disappointing results? Eg MRE11—not much literature on risk• Risk for AR conditions e.g. ATM

- All principles of GC for BRCA1/2 apply BUT amt of info per gene-abbreviated

- “Increasingly we will be the recipients of data that we did not anticipate, or perhaps, even seek to know. Accordingly we will be in the uncomfortable position of reacting to that data on the basis of an immature & incomplete understanding of what that data mean.” D.Hayes, MD FASCO pres.elect

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Assessment• History tool are not uniformly or reliably evaluated according to NCCN or USPSTF guidelines for high risk

identification or referral for genetic counseling/testing. As a consequence, patients who would benefit from earlier-onset screening, additional screening modalities and/or chemoprevention do not have access to this care. If patients are not first identified as high-risk for breast, colon or other cancers, they are never given the opportunity to make informed decisions about their options for early detection or prevention (i.e.,we can’t help the high risk patients unless we find them first) (Bellcross, et al., 2009).

• In addition, when family history questions are asked and nothing is done with the information, patients may falsely feel their reported history, by default,was not a concern. This is also the source of liability as information that could significantly impact patient risk and management is elicited and documented by the clinic/provider but not addressed.

• The added cost in lives, unnecessary advanced stage cancer treatment, unnecessary screening and subsequently unnecessary health care dollars could be mitigated with an automated identification system (stewardship, putting the patient first).

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Pilot project @PBC• 3000 surveyed• 23% answered “yes”-PCP& pt notified• ~8% followed up with recommended GC w/in 1yr• Many cited lack of support of PCP or ‘PCP did NOT bring this up’

as reason

Practical Implicataions:Enhance collaboration with PCP + implementation of simple EMR based tool for pt ID

Family History Screening Tool + Referral Letter

Primary Care Providers

Patients

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Who?Screening Question:Do any of the following apply to you or a close family member-blood relative (parent, sibling, child, aunt, uncle, niece, nephew, OR grandparent)?* Three or more relatives on the same side of family (either your mother’s side or your father’s side) with breast cancer (Y/N)* Breast cancer at 50 or younger and at least one other relative on same side of family with breast cancer(Y/N)* Ovarian cancer at any age (Y/N)* Male breast cancer (Y/N)* Breast cancer at age 45 or younger (Y/N)* Breast cancer and Jewish ancestry (Y/N)

If any of the responses = yes, patient is eligible for consult to genetic screeningAn alert/flag will appear if the patient meets eligibility criteria indicating that it is recommended that the patient be referred to genetic counselingRemove flag for that particular screening criteria if screening done within the past 365 daysScreening questions will be done every 3 years for updatesIf all responses = no, screening questions should be asked/documented annually

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Who cont?Screening Questions:1. Do you have a first-degree relative (mother, father, brother, sister or child) with any of the following conditions diagnosed before age 50?* Colon or rectal cancer (Y/N)* Cancer of the uterus, ovary, stomach, small intestine, urinary tract (kidney, ureter, bladder), bile ducts, pancreas or brain (Y/N)

2. Have you had any of the following conditions diagnosed before age 50?* Colon or rectal cancer (Y/N)* Colon or rectal polyps (Y/N)

3. Do you have three or more relatives with a history of colon or rectal cancer (This includes parents, brothers, sisters, children, grandparents, aunts, uncles and cousins) (Y/N)If any of the questions above = Yes, then patient qualifies to be referred for genetic assessment

An alert/flag will appear if the patient meets eligibility criteria indicating that it is recommended that the patient be referred to genetic counselingRemove flag for that particular screening criteria if screening done within the past 365 daysScreening questions will be done every 3 years for updatesIf all responses = no, screening questions should be asked/documented annuallyInclude link to the reference sources of the screening tool. See tab called References

FUTURESNPs; epigenetics; microbiome

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Over half of familial/heritable breast cancer NOT addressed by panels

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Precision Medicine in Prevention:

“ He is a better physician that keeps diseases off us, than he that cures them being on us; prevention is so much better than healing because it saves the labour of being sick.”

Thomas Adams, 1618

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