Genetics in Palliative Care (PC)
Joann Bodurtha MD MPH
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine

Thanks to my colleagues, patients, and the Sapporo community

I have no financial relationships todisclose, nor will I discuss offlabel or investigational usage ofdrugs.

My 1o career goal is to help makegenetics work to help people andimprove health.

Terms• Family History (FH): A record of medical information and stories/ecological family
information about an individual and their biological family• Genetic counseling (GC): The process of helping people understand and adapt to the
medical, psychological and familiar implications of genetic contributions to disease• Predictive genetic testing (GT): The use of a genetic test in an asymptomatic person topredict future risk of disease. This is best done after a relative with cancer has been
diagnostically tested to identify the predisposing gene within the family• DNA Banking: The collection and long term storage of genetic material• Genetic testing can involve complex and emotional decision making• Banking gives relatives time to seek counseling and carefully consider their options,
without feeling pressured to pursue testing prior to a loved one dying• According to previous studies, many physicians (oncologists/palliative care providers)
do not offer DNA banking and many are not aware of its availability

What do you think? What would you do?
The patient is a 32-year old woman dying withbreast cancer in palliative care. Her mother diedof some “female” cancer in her 30s when thepatient was a young child. You overhear her ask
her husband, “Do you think our 5-year olddaughter will get cancer?”How do you like to get genetic information?

Where in the cancer care continuum does themother’s question get addressed?
• Optimally upstream as part of active cancer careor preventive primary care with FH review• But, if it comes up in palliative care,
how do you handle it?

Alternatives• Ignore?
• Encourage the patient to talk with her oncologist, primary care doctor, nurse,
social worker, caregiver, child’s pediatrician etc. about any genetic concerns?
• Ask?
• What are your concerns for your daughter?
• Are you worried about cancer risk in your family?
• Have you ever talked with someone about your family history of cancer?
• Do you want to talk with someone about your cancer and family history?
• When would be a good time to talk about this? Learn about resources? Consider areferral to a genetics professional, genetic testing, and/or DNA banking?

Cultural humility is vital.

Key points• Patients have• different languages• religious and scientific beliefs• ways of understanding their illness experience• Culture fundamentally shapes how patients andfamilies make meaning out of illness, diagnosis,
suffering, and dying.

Key points• Many dying individuals voice concern for thehealth of their surviving relatives.
• Genetic testing is frequently more useful wheninterpreted in the family context.
• Reality is under-recognition of family history
implications prior to death.
• Genetic testing will continue to improve.

Key points• Good communication practices can help inunderstanding patient & family preferences/needs.
• CA genetic counseling & testing are becoming
important services in progressive cancer care – withdiagnosis, in survivorship, at end of life, and withincorporation of family history throughout journey.
• Ethical frameworks influence what and how wecommunicate, e.g. what tests & treatments we offer.

Key points• DNA banking (consideration of genetic testing)can be legacy act for the dying patient and costs~150 US$.
• DNA banking may give relatives time to seek
counseling and consider testing decisions.
• Performing testing earlier in life likely preferable,
but it often has not happened.

We learn from each other across families, miles, and years.

40 years ago @ Kawatana Byoin• 3 teen-age brothers dying with
Duchenne muscular dystrophy• What thoughts and feelings doyou bring to the table?
• Genetic counseling with mother atdiagnosis in first son• Hoping for best without discussion

Mental model
Family Health History(FH) matters.
FH discussion is a central family
communication tool to improve publichealth prevention, family health, andwell-being, voila

More healthy
birthdays!

http://www.cdc.gov/genomics/resources/diseases/family.htm

What have you done lately about FH in your own family
and oncology work?

•Talking it up?
•Writing it down?
•Passing it on?

What We Know about Family Health History• Accuracy is OK for close relatives (95% for breast CA, 90% for colon CA) (Ziogas et al., 2003)• Has potential to motivate positive behaviors• Generally does not increase anxiety• Clinicians vary with respect to FH collection:• Residency training and length in practice• Time with patient• Available FH collection tools• More likely to report FH to your doctor if you are:• Female• Have insurance• Moderate to high SES

NIH Consensus Conference, 2009

Challenges with FH- Small family size
- Small number of people of the susceptible sex in sex-specific CAs.
- Inaccurate/incomplete/missing information about the FH (e.g.
adoption, non-paternity).
- Parents and other 1st or 2nd degree relatives of pediatric patients areoften young, and CA may not have developed yet.
- Family communication issues- Emotional/social/cultural (shame, guilt) issues

Goal: Tier risk
Who needs what?
Assessment

Family Hx

Risk Classification

Intervention

AverageStandard prevention
recommendations

Moderate(“Familial”)

Personalized prevention
recommendations

High/Genetic

Referral for genetic evaluation
with personalized prevention
recommendations

SIDE questions• Mother’s side

Father’s side

Any Similar problems?
Any Inherited conditions in family?
Any unexplained Deaths < 50 yoa?

Any Extraordinary lab results, health events, genetic
testing?

Electronic Tools

Image courtesy of https://familyhistory.hhs.gov/fhh-web/home.action

Where does it fit in palliative care?
High Risk
for Cancer

Cancer Diagnosis

Genetic Counseling

Tailored Treatment and Prevention

Discussion with Family Members

Improved Public HealthFamilial Disease• ~5-10% of cancers & heart disease have a major genetic component• ~8% of children with CA have a germline mutation• National guidelines re high-risk families• In Japan• HBOC• Lynch syndromeSome Japanese reports (in English!)• In 2012 Asian ARCA survey, Japan reported not offering
chemoprevention, contralateral mastectomy, prophylactic
mastectomy and did offer annual MRI, RRSO with self-pay for
genetic testing offered at 80 centers offering full services
Nakamura et al 2015

• 2010 survey of breast cancer specialists – ¼ of facilities
providing CA genetic services, 36% aware of potential risk of
HBOC, 14% recommended young BC patients to visit genetic
specialists Bando 2014

Some Japanese reports (in English)• Patient-completed questionnaires for assessment of hereditary
gynecologic CAs have clinical utility Masuda et al 2017
• In 2015 survey, 8% of CA departments conducted universal screeningfor Lynch syndrome Yamano et al 2017
• 40 individuals from 33 families with Lynch syndrome – 75% advised
their relatives to seek medical assessment, tended to speak withspouses 1st, “to avoid feeling the same sorrow” was most common
reason for encouraging relatives Ishii et al 2011

PTEN hamartoma syndrome
Cowden and Bannayan-Riley Ruvalcaba syndrome
PTEN, SDHB, SDHD, and KLLN mutations
Autosomal dominant with increased breast, endometrial, thyroid and other CAs
Some patients with large heads, intellectual disability, penile freckling

trichilemmomma

oral mucosal papillomatous growthExample of a common CA & criteria that warrant
assessment for cancer risk
CancerWhen to refer to genetic counselling

Syndromes to consider

Breastcancer• Dx at age ≤50•Triple-negative dx at age ≤60• ≥2 primary breast cancers in the same person• Ashkenazi Jewish ancestry and breast cancer at any age• ≥3 cases of breast, ovarian, pancreatic, and/or aggressive prostate cancer
in close relatives, including the patient• Breast cancer and one additional LFS tumor in the same person or in two
relatives, one dx at age ≤45• Breast cancer and ≥1 PJ polyp in the same person• Lobular breast cancer and diffuse gastric cancer in the same person• Lobular breast cancer in 1 relative and diffuse gastric cancer in another,
one dx at age <50• Breast cancer & 2 additional Cowden syndrome criteria in the same person•HBOC, OMIM: 604370, 612555;
LFS, OMIM 151623• PJS, OMIM 175200• HDGC, OMIM 137215• Cowden, OMIM 158350

Who decides in family-centered care?
Cancer patient’s top 3 questions*

1. Am I going to die?
2. What will my treatment be and how long will it
take? (because I can't afford to miss time from work)
3. What will happen to my children? Will they getcancer?

*Lillie Shockney, JH CA survivorship leader

The PC setting dynamics• Many people with advanced CA will have contact with PC healthprofessionals for holistic care at the end of their lives.
• Discussions and assessment of cancer FH do not always take place inthis phase of the patient’s illness and the reasons include:- Low levels of confidence of staff in dealing with genetic issues- Perceived inappropriateness of the topic at this time
- Potential distress for patient and family- Decisions regarding genetic testing/DNA banking are complex and canhave profound emotional, familial and financial implications on thoseaffected (like cancer itself)Why Should We Pursue It?
- Many dying patients voice concern for the health & well-being ofsurviving relatives- It may serve as a “teachable moment” about familial risk andmotivate healthy behaviors for family members- It may be the last opportunity for an:- elderly relative to document the family history of CA for future generations- affected family member to give blood to enable other family members toundergo predictive genetic testing- It has also been suggested that disease progression, especially being
told that CA is incurable, can provoke fears about genetic disease thatare not given a voice.

Listening and providing the evidence• What are genetic realities in PC setting?
• What do patients want?
• What do PC providers know?
• How do we enhance family history communication, risk perception,and prevention behaviors with individuals and families?

Our own work in PC inpt. settings
Structured interviews with chart reviews
VCU – 43 patients in 2008

Johns Hopkins – 75 patients in 2016-17• 74% enrollment, ½ AfricanAmerican, mean age – 55y• Of the 15 most frequent PC
admission diagnoses ~1/3 had asignificant genetic component• 9/43 (21%) dying patients had astrong genetic risk. None of thepatients had prior GC, testing or
DNA banking• 75% enrollment; 27% black,mean age – 64y , 55% male
• At least 27/75 (36%) with highCA risk for 1st, 2nd degree
relatives (Hampel et al criteria)• 14/75 (19%) had no FH chart
documentation

Key findings – 75 participants with cancer, PC
consultation, interview and chart review• Minimal referrals/visits for genetic counseling (2/75; one in distantpast and one related to pregnancy) from chart review• Minimal germline genetic testing (1 for BRCA, 1 forhemochromatosis); 2/75 (3%)from chart review• Patients did not make clear distinction between germline vs. somatic
testing when answering that they had had genetic testing – 11/75(15%); per chart review, 27/75 (36%) with somatic testing, 2/75(3%)
with germline testingPatient preferences re resources
For genetic testing

For sharing test results with family• Conversation with MD/nurse(83%)• Written materials (71%)• Appointment with genetic
specialist (69%)• Not interested (3%)• My health professional talk withthem (51%)• A letter from my healthprofessional (39%)• Written material (29%)• Would not share (1%)

Genetic testing – awareness and attitudes
about Angelina Jolie’s HBOC
• 54% men and 76% womenaware of story• 72% thought she did the rightthing in sharing her story

Palliative care physician perspectives• 2008 US survey of palliative care oncologists (n=133) in AAHPM• 37% response, 1/3 female and mean age – 53.8 yrs• ~80% assessed genetic risk for at least one patient• None had banked DNA in preceding 12 mos.
• ~2/5 said they were “not qualified at all” to recommend DNA banking• ~1/5 responded correctly to all the content questions• ~3/5 wanted Web-based risk assessment tool & genetic counselor on
staffTalking about Cancer in the Family
Could Save Your LifeDo I know my Kin Facts?
A guide for Jada Doe and my family

Why do you need to talk with your family?

Basic Principles of Communication• You cannot not communicate• Communication is a two-way activity• Words & actions are interpreted by the receiver• Much communication is nonverbal• Listening is the mostimportant part ofcommunication

What is the health and cancer story in your family?
Did men and women both
talk openly about healthproblems?
Did your grandparents talkabout their healthproblems?

Were they afraid to say theword “cancer”?

Does your family take on
healthy habits together?

Did anyone in your family
have cancer? What wasthat experience like?

Be a good communicator• Show them you arelistening & focus on
the moment• Affirm• Say, “Uh, huh”
• Say, “I see”

• Probe• Say, “Tell me more”• Rephrase what you hear
• Say, “What I hear you saying is…”
• Say, “It sounds like…”• Be a mirrorAsk• What do they already know?
• “What do you know about our family
history of cancer”• “What do you know about cancer risk
in our family?”• “What do you know about how toprevent cancer in our family?”

Can we talk about what I
learned from the Kin Fact
program about family cancer
risk?

How can I be a good communicator?
• Listen– Affirm• “Uh, huh”
• “I see”– Probe• “Tell me more”– Rephrase what your hear• “What I hear you saying is…”
• “It sounds like…”• Be a mirror

Make a Plan with your Family Member• “Who else do we need totalk to?”• “What else do we need toknow?”• “When should we talkabout this again?”• “What are we going to do
to lower cancer risk?”

Remember Your Kin Facts• Families share genes, behaviors and environmentsthat can lead to breast and colon cancers• Your family can reduce their risks• Talk with your relatives about the family cancer story
and how to stay healthy

Results and Next Steps• Results• intervention effect +• OR =2.73 (95% CI 2.01,3.71) for gather• OR =1.85 (95% CI 1.37,2.48) for share• Communication frequency increased (1.67 vs. 1.54)• Differences not modified by age, race, education, family history• Women with low genetic literacy did not show differences for gathering
information• Learn about the process and refine the intervention

Findings from the literature• Some groups may trust health information from family +/or internet
more than MD• Family communication may be more understandable (accurate?)because not medical jargon• Stories may have stronger effects on patient decision-making• “Communicomics” occurs within micro (clinical) and macro (media)
environments as individuals bond and bridge within and acrossfamilies and networks

The legacy of cancer: why a health promoting
approach is so important in PC – Baker et al 2015
• 27 interviews in UK with advanced CA patients-patients had more + attitude to CA than relatives-legacy work that their situation would positively impact othersin the future-supported a health promotion approach in which PC extends topeople that matter to the patient-extend concept of making every contact countMoving Forward• Genetic counselors, medical geneticists, and genetic nurses facilitate
comprehensive genetics evaluations, assist in test selection, provide informed
consent, and education patients & family members about indications for andcosts of testing and banking.
• No consensus on who should be approached or any specific communication
strategies• “I’d like to talk with you about your family health history. Some healthconditions tend to run in families and knowing your health history and seeing
if it is connected to your illness could help others in your family to stayhealthy. Most diseases are not strongly genetic, but sometimes it is helpful tohave a genetic test or store a blood sample for testing later.”

Story 1: hereditary cancer••

The patient was a 75-year-old man diagnosed at age 58 withprostate cancer who presented with pancreatic cancer at age 74.
His family history included a son diagnosed with an ampullarycarcinoma at the age of 43, a mother and maternal aunt who diedof ovarian cancer in their 50s, and a maternal grandmother withbreast cancer at age 55.

Better ending?
•••

The patient underwent a 29-gene hereditary cancer panel that
included the APC, ATM, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1,
CDK4, CDKN2A, CHEK2, EPCAM, MEN1, MET, MLH1, MSH2, MSH6,
MUTYH, NBN, PALB2, PALLD, PMS2, PTCH1, PTEN, RAD51C, RET,
SMAD4, STK11, TP53, VHL genes.
Within days of the genetic testing being ordered, the patient
rapidly declined and expired before the results were available. The
patient was found to have a pathogenic PALB2
c.1671_1676delinsGC (Phe557Leufs*3) mutation.
This result was disclosed to the patient’s wife and daughter.

More Challenges in End-of-Life Genomic Testing• Improved genetics training for all health-care professionals• Avoiding “one-size-fits-all” policies• Promotion of individual and family choices

Reasons for DNA Banking• Simple and inexpensive step to preserve genetic legacy to benefit the patient’s family and future
generations by providing access to information in the future that can help them better
understand their own risk for disease.
• Patient may have a specific health condition and is concerned that other family members might
be at risk for the same problem.

• Current technology has failed to find a genetic cause for what appears to be an inherited diseasein the patient’s family.
• Correct interpretation of DNA test results in a family member may only be possible throughtesting of one’s DNA.

• Patient has a terminal illness and there is no time for standard genetic evaluation or testing.
• Genetic testing is not feasible, affordable, and/or not available to one as an affected individual
right now, but may be available in the future.

Our JH PC study and DNA banking~40% could give some definition~85% had heard almost nothing, very little about it~5% had banked their own DNA~5% believed a relative had~72% would consider banking their DNA~45% willing to pay something to bank their DNA

Voluntariness of Consent• Dying patients vulnerable• Consent should be voluntary• Some degree of guilt, feeling of obligation probably unavoidable• Careful discussion can help prevent coercion

Your Cancer Genetics Plan
• Know your Family History – talk it up, write it down, pass it on• If Ashkenazi Jewish, young age, 2 or more relatives with BC/OC (esp.
premenopausal) multiple CAs, talk with your PCP• If multiple CCs, polyps in FH – talk with your PCP• If you have CA, discuss with your oncologist/surgeon• It is getting more complex – additional tests, need informed consent andunderstanding of test limitations• High risk screening recommendations - different and evolving• 1-800-4CANCER, FORCE www.facingourrisk.org, AACR
• Take care of yourself• Consider genetic counseling (NSGC.org)

Key points• Family history involves social and genetic determinants• Precision medicine needs matching with precision communication• Technologies will advance &need trusted systems so disparities do
not increase• Communication is central to well-being, healthcare, and healthbehaviors• Knowing your risk can provide prevention opportunities, focus
screening, and tier strategies

When to refer to genetics?
• Positive 3, 2, 1 criteria:- Three affected relatives with the same/associated CAs- Across two generations- With at least one person affected age <50 years.

The Present/Future• Screening tailored to risk (e.g. MRIs with mammograms)• Prevention tailored to risk (e.g. Tamoxifen/Raloxifene/aromataseinhibitors, preventive surgery)• Therapies tailored to gene tests (e.g. choice of chemotherapy drugs,
dosing of radiation)• Just like we have moved forward with open discussions of cancer,
smoking harms, palliative care and death, we may one day better
integrate family history and genetic concerns in palliative care

Continuing support, survivorship, and lifelong
issues• Ask-tell-ask• Listen• Negotiate• Give hope
• Consider developing systems
that give options so families
have choices

Thanks for listening
and being patientand family-centered.
• Thanks to my patients,
colleagues, and Japanese
friends.

6/27/201765

Resources• 1. Fast Facts: Genetic Screening and DNA Banking at the End of Life #206. Quillin J, Bodurtha J,
Smith T• 2. Genetics Assessment at the End of Life: Suggestions for Implementation in Clinic and future
research. Quillin J, Bodurtha J, Smith T• 3. Exploring Hereditary Cancer Among Dying Cancer Patients – A Cross-Sectional Study ofHereditary Risk and Perceived Awareness of DNA testing and banking. Quillin J, Bodurtha J,
Siminoff LA• 4. A practice guideline from the American College of Medical Genetics and Genomics and the
National Society of Genetic Counselors: referral indications for cancer predisposition assessment.
Hampel H, Bennett R• 5. Hereditary Cancer, March 2015: A presentation by J Quillin, H Creswick• 6. Prevention Genetics https://www.preventiongenetics.com/DNABanking/reasons.php• 7. Germline Mutations in Predisposition Genes in Pediatric Cancer. Zhang J et al. NEJ Med 2015;
373:2336-2346 December 10,2015.
http://www.nejm.org/doi/full/10.1056/NEJMoa1508054#t=articleDiscussion

Resources• Genetests.org; Genetic Testing Registry; ASCO; ACMG; NSGC
• Lakhani NS1, Weir J, Allford A, Kai J, Barwell JG. Co triaging family history of cancer during palliative
care enable earlier genetic counseling intervention? J Palliat Med. 2013 Nov;16(11):1350-5.
• Qullin J et al. Genetics assessment at the end of life: Suggestions for implementation in clinic andfuture research. Jnl Pall Med 2008; 11:451-458• Quillin J et al. Exploring hereditary cancer among dying cancer patients – A cross-sectional study ofhereditary risk and perceived awareness of DNA testing and banking. J Gen Counsel 2010; 19:497-525• Quillin J, Bodurtha J, Siminoff LA, Smith TJ. Physicians’ current practices and opportunities for DNA
banking of dying patients with cancer. Jnl Onc Pract 2011; 7:183-187• Quillin J, Bodurtha J, Smith T. Genetic screening and DNA banking at the end of life #206. Fast Facts andConcepts• Skirton H et al. A legacy for the children – attitudes of older adults in the United Kingdom to genetic
testing. J Clin Nurs 2006; 15:565-573• Stephen H et al. End-of-life care discussions with nonmalignant respiratory disease patients: asystematic review. Palliat Med 2013; 16:555-65.

Genetics Resources• Genetics Home Reference http://www.ghr.nlm.nih.gov• GeneReviews, GeneTests• The Alliance (1-800-336-GENE)• OMIM®(On-line Mendelian Inheritance in Man)
• Smith’s Recognizable Patterns of Human Malformation (Jones K, Saunders pub)
• U.S. Surgeon General’s Family History Initiative www.hhs.gov/familyhistory/• CDC www.cdc.gov/genomics/public/fam-hist.htm• Massey Cancer Center http://www.massey.vcu.edu/pdf/FamilyHealthHistory.pdf• CancerNET• HuGE NET – www.cdc.gov/genetics/hugenet/default.htm• National Guidelines Clearinghouse – www.guideline.gov• National Society of Genetic Counselors – www.nsgc.org• Genetic counselor directory National Society of Genetic Counselors http://www.nsgc.org• Laboratories offering DNA banking http://www.genetests.org