TELEMEDECINE

Genetic testing for breast cancer

Chirag Jani MD. ABHPM. FACP

Medical Director

Chairman, COC and NAP BC

Phoebe Cancer Center

Agenda

• Defining Telemedicine • History • Successful Uses

• Our Project and outcomes • Regulatory Information • Requirements for Telegenetics • Current and Future state

Telemedicine

• Means "distance healing“.

• Derived from a Greek word "Tele" meaning "distance" and a Latin word "mederi" meaning "to heal“.

• Use a specific technology to provide healthcare services

Telemedicine is the future of global healthcare.

Telehealth vs Telemedicine?

Per WHO:

Telehealth-uses computer-assisted

telecommunications to support management,

surveillance, literature and access to medical

knowledge

Telemedicine-solely to diagnose and treat

patients

Used interchangeably by most

“TELEGENETICS PROVIDES HEALTHCARE WHERE THERE IS NONE AND IMPROVES THE HEALTH CARE WHERE THERE IS SOME”

History of Telemedicine

1905

William Einthoven transfers

electrocardiograms electronically

1960s

First used by NASA to monitor health of astronauts in space

1990s

Telemedicine matures; wide-

spread acceptance of teleradiology

practices

Now

Telemedicine seen as a viable means

for improving access, decreasing

costs.

Telemedicine Application

Home Care and Ambulatory

Remote Consultation and Critical Care Monitoring

Medical Education and Public Awareness

Second Opinion/TELEGENETICS

Telementored Procedure/ Robotic Surgery

Disaster Management

Types of Telegenetics

Real-time (synchronous)

Store and Forward (asynchronous)

Specialties in Telemedicine

10

Internal Medicine Neurology Oncology/Hematology Genetics Ophthalmology OB/GYN Pediatrics Psychiatry Pulmonology Rheumatology Surgery Urology

Allergy/Immunology Anesthesia Cardiology Critical Care Dermatology Otolaryngology (ENT) Emergency Medicine Endocrinology Family Practice Gastroenterology Infectious Diseases

“60-80 % of ER, urgent care, and doctors visits can be handled safely and effectively over the phone. -American Medical Association

? 11

“To date, no studies have identified any patient subgroup that does not benefit from, or is harmed by mental healthcare provided through remote video conferencing.”

12

Growth of Telemedicine Globally

$13.8 billion

2012 Market Size

$9.8 billion

2010 Market Size

278% Growth Rate Expected Between 2010-2019 Research

Advantages of Telegenetics

• Resource utilization

• Early intervention

• Avoids unnecessary transportation

• Community based care

• Medical education and research

• Cost saving

• Improved patient documentation

• Increased range of care and education.

Resource Utilization

• In underdeveloped countries doctor population ratio is 1:20000 in comparison to 1:500 in developed nations, and these doctors are not distributed equally.

• 80% of population lives in rural and semi urban areas.

• Telemedicine can help in cost effective utilization of meager resources and of the same time can decrease patient work load on few referral centers.

We look more like this

….than that

OUR PROJECT

4 Year Snapshot

Telemedicine System

• ACTUALLY WHAT HAPPENS DURING A TELEMEDICINE PROGRAM?

Clinical Process in our Clinic

CLINIC

Gene Breakdown

Evaluation: Financial Impact

• Utilization patterns

• Missed work/school days

• Direct and indirect cost savings

• ROI

Early Intervention

• There are factors that inhibit the continuity of care. Issues such as geographic location, inclement weather, socioeconomic barriers.

• Patient apathy are significant factors that delay and even prevent the specialty care.

• By providing these sites with the ability to quickly access specialty consultation services.

• Patients are able to reap the benefits of early intervention while the health care system maintains quality service and clinical efficiency.

Avoids Unnecessary transportation

• Patient can discuss the issues on Video Conferencing with the consultant.

• Even the vital parameters and be captured with the help of devices and sent to doctor.

• Unnecessary referral and patient transport can be definitely avoided.

Community base Care

• People like to receive high quality care in their local community.

• This reduces travel time and related stresses associate with many referrals.

Barriers of Telecommunication

• Low or small bandwidth. • Neither telephone lines nor electricity in rural and

remote areas. • Satellite transmission can help but it is very costly. • Unstable electricity supply. • Patient’s fear and unfamiliarity. • Financial unavailability. • Lack of basic amenities. • Literacy rate and diversity in languages. • Quality aspect. • Government support.

Sporadic vs. Genetic

• Germline – the genes you are born with

– Can be passed on to relatives

– Does not mean that disease will happen

– Increased risk of disease

– There is no one “breast cancer gene”

• Somatic – changes in tumors that are acquired over time

– Can not pass on to relatives

– Can be tested as part of decision making for therapy for cancer

Germline vs Somatic Genetics

• Breast cancer <45

• Ovarian cancer cases (particularly high grade serous)

• Male Breast Cancer

• Breast and ovarian cancer in a single lineage

• 2 or more women with breast cancer <50

• Ashkenazi Jewish with breast or ovarian cancer

• Breast cancer < 60 and triple negative

• Bilateral breast cancer <60

• Pay attention to pancreatic cancer and high grade

prostate cancer

• Ashkenazi Jewish individuals?

Who should be considered for testing?

• Risk Assessment

• Disease Prevention

• Therapeutics

Germline genetic testing as a paradigm

for individualized care

BRCA1/2 as the prototype

Increased risk of other cancers:

Male breast cancer BRCA2>BRCA1

Pancreatic cancer BRCA2

Prostate cancer BRCA2

Melanoma BRCA2

Breast cancer: 50%-70%

Second primary breast cancer: 40%-50%

Ovarian cancer: 15-55% BRCA1>BRCA2

BRCA1/2-associated cancers: lifetime risk

Genetic testing has become complicated….

Single nucleotide polymorphism panels

• Not comprehensive sequencing of genes – such as BRCA1/2

• Not a stand alone for those with a strong family history

• Some change in reclassification (change in how you

consider someone from a risk perspective)

• Calibration: How closely the predicted probabilities agree

with the actual outcome

• Clinical utility (or actionability?) – Will more women take tamoxifen?

– How should this impact screening in the era of changing screening

recommendations?

• Ongoing studies

Key Points

In the US - this has become very complicated….

Gene Myriad MyRisk

Ambry Cancer Next

Invitae GeneDx Uwash BROCA

Fulgent*

# of genes 25 28 28 30 50 110

APC x x x x x x

ATM x x x x x x

BMPR1A x x x x x x

BRCA1 x x x x x x

BRCA2 x x x x x x

BRIP1 x x x x x x

CDH1 x x x x x x

CDK4 x x x x x x

CDKN2A x x x x x x

CHEK2 x x x x x x

EPCAM x x x x x x

MLH1 x x x x x x

MSH2 x x x x x x

MSH6 x x x x x x

MUTYH x x x x x x

NBN x x x x x x

PALB2 x x x x x x

PMS2 x x x x x x

PTEN x x x x x x

RAD51C x x x x x x

SMAD4 x x x x x x

STK11 x x x x x x

TP53 x x x x x x

Gene Myriad MyRisk

Ambry Cancer Next

Invitae GeneDx Uwash BROCA

Fulgent*

BARD1 x x x x x RAD51D x x x x x MRE11A x x x RAD50 x x x

NF1 x x VHL Renal/PGL x x x x

MEN1 x x x RET PGL x x x

PTCH1 x x PALLD x XRCC2 x x x CHEK1 x x AXIN2 x x FANCC x x

ATR x x BAP1 x x

GALNT12 x x HOXB13 x x POLD1 x x PRSS1 x x

RAD51A x x SDHB Renal/PGL x x SDHC Renal/PGL x x SDHD Renal/PGL x x AKT1 x

CTNNA1 x FAM175A x

GEN1 x GREM1 x PIK3CA x POLE x

PPM1D x TP53BP1 x

*Rest of genes on Fulgent: BLM, BUB1B, CTNNB1, CYLD, DDB2, DICER1, EGFR, EGLN1, ERCC2, ERCC3, ERCC4, ERCC5, EXO1, EXT1, EXT2, FANCA, FANCB, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, GPC3, HRAS, KIF1B, KIT, MC1R, MPL, MSH3, NF2, PDGFRA, PICALM, PMS1, PRKAR1A, PRKDC, PTPN11, RB1, RBBP8, RBM15, RECQL4, ROBO2, SBDS, SLX4, SMARCB1, SUFU, TERT, TSHR, TYR, WRN ,WT1, XPA, XPC, XRCC3

Gene Ambry

Renal or PGL

Fulgent*

FH x x FLCN x x MAX x x MET x x MITF x x SDHA x x

SDHAF2 x x TMEM127 x x

TSC1 x x TSC2 x x

Assess patient

Test for most likely

gene(s)

Disclose result and reassess

Test for most likely

gene(s)

Revolution of genetic testing

Assess patient

Send multigene

panel

Disclose result and reassess

New approach?

INTERVENTIONS

What is actionable?

• Something that potentially could be acted upon

• It does not mean that it is acted upon

• It does not mean that such action benefits a patient

• Actionability = clinical utility

• Critically important that all this be studied

• More cost effective (for the testing) to do multigene

rather than serial testing

• Patients (and providers!) can get testing fatigue

• The same cancer can be seen with different genes

mutations

– Ovarian cancer in both BRCA1/2 and Lynch

– Uterine cancer in Lynch and Cowden

– Breast in Li-Fraumeni and BRCA1/2

• Isn’t more better?

Why do this?

• High penetrance and moderate penetrance genes

are on one panel

– Implications for counseling

– Keeping track of it all

– Don’t we recognize clinical syndromes?

• (And if we don’t – what does it mean?)

• Variants of uncertain significance

• Clinical utility: order tests you will act on

– At least actionability

Domchek et al, JCO 2013

Potential Issues

• Screening and prevention

– Need to understand risks and benefits

– What age to start screening?

– What screening?

– What age to have preventative surgery?

– What to do with “unexpected” high penetrance mutation

• When we find things we don’t expect, what should we do?

Clinical utility

• Therapeutics

– Prognosis: may impact administration of adjuvant

therapy

– Drug development/selection

– Will tumors with mutations in these other genes be

sensitive to specific types of drugs?

Clinical utility

Case 1- Medical Oncology

Relationship Diagnosis Age Cancer Site TNBC Histology

Mother 80 Colon

Patient 59 Ovarian

Sister 54 Breast, Invasive No

Uncle Maternal #1

Lung

Uncle Maternal #2

Lung

PALB2 Cancer Risk

PALB2 Management

PALB2 Management

©2019 Myriad Genetics, Inc. All rights reserved.

Case 2 Medical Oncology

Relationship Diagnosis Age Cancer Site TNBC Histology

Great Aunt Maternal

65 Invasive Breast Cancer

No

Mother 70 Leukemia

Mother 80 Non-Hodgkins Lymphoma

Patient 60 Invasive Breast Ca

Yes

©2019 Myriad Genetics, Inc. All rights reserved.

BRCA1 Cancer Risk

©2019 Myriad Genetics, Inc. All rights reserved.

BRCA1 Management

©2019 Myriad Genetics, Inc. All rights reserved.

BRCA1 Management

©2019 Myriad Genetics, Inc. All rights reserved.

BRCA1 Management

• Genetic testing can be very useful to patients and their family members – Both the prevent and to treat cancer

• Genetic testing is continuously evolving

• BRCA1 and BRCA2 mutations are the most commonly found and we have reasonable data on how to manage

• New genetics tests are often less clear in terms of how to change patients care – and improve patient outcome

• Variants of unknown significance should NOT be managed as mutations

• In the face of rising prophylactic mastectomies, we need to emphasize to patients how mutations in these genes are different from those in BRCA1/2

Conclusions

Robotics

Remote Surgery

Live Monitoring

via Cell Phones

Wi-Fi Smart Scale

Otoscope Blood Pressure Monitor

Bluetooth Stethoscope

Blood Glucose Meter

Digital Thermometer

Increased Access

to health care

for all

At Home, at the Office, on the Go, at a Kiosk