College of American Pathologists Welcome to the PHC Webinar Series © 2010 College of American Pathologists. All rights reserved. 1 This lecture on “The

College of American Pathologists

Welcome to the PHC Webinar Series

© 2010 College of American Pathologists. All rights reserved. 1

This lecture on “The Why, What and How of Identifying Patients at Risk” is given by

Alexis B. Carter MD, FCAP

Your host is Jill Kaufman, PhD.For comments about this webinar

or suggestions for upcoming webinars, please contact

Jill Kaufman at [email protected]

THE WEBINAR WILL BEGIN MOMENTARILY. ENJOY!

www.cap.org

Identifying and Communicating Risk for Hereditary Cancer SyndromesAlexis B. Carter, MD, FCAP

September 8, 2010

CAP Personalized Healthcare Webinar Series


Alexis B. Carter, MD, FCAP

• Director of Pathology Informatics, Department of Pathology and Laboratory Medicine, Emory University School of Medicine

• Assistant Professor, Department of Biomedical Informatics, Emory University School of Medicine

• Board certified in Anatomic, Clinical and Molecular Genetic pathology

• Test Directory Editor, Association for Molecular Pathology



Alexis B. Carter, MD, FCAP

• Member, CAP Personalized Healthcare Committee

• CAP Liaison to the World Association of Societies of Pathology and Laboratory Medicine

• Training and Education Committee Chair, Association for Pathology Informatics



Disclaimer

The College does not permit reproduction of any substantial portion of the material in this Webinar without its written authorization. The College hereby authorizes attendees of the CAP Webinar to use the pdf presentation solely for educational purposes within their own institutions. The College prohibits use of the material in the Webinar – and any unauthorized use of the College’s name or logo – in connection with promotional efforts by marketers of laboratory equipment, reagents, materials, or services.

Opinions expressed by the speaker are the speaker’s own and do not necessarily reflect an endorsement by CAP of any organizations, equipment, reagents, materials or services used by participating laboratories.



Disclosure

• I have no financial interests in any entity or organization, other than the one by which I am employed (Emory)

6© 2011 College of American Pathologists. All rights reserved.


By the end of this webinar, you should…

• Understand importance recognizing and communicating risk for hereditary cancer syndromes (HCS)

• Recognize warning signals for HCS in generalo Specific warning signals for common HCS

• Have a suggested plan for o Communicating risk to physicianso Documenting that communicationo Handling pathology reports



This webinar will not cover:

• How to diagnose tumors associated with HCS

• The individual genetic tests used to confirm diagnosis of HCS



Disclaimer

• Suggested plans of action should be taken as suggestions onlyo Use only if appropriate to your practice

environment and patient population

• This is not and should not be used as legal advice



Definitions

• Hereditary Cancer Syndrome (HCS)o Hereditary condition in which genetic change(s)

increases an individual’s likelihood to develop cancer in his/her lifetime over that of individuals without the genetic change(s)

o Suspected when cancer occurs−At a younger-than-expected age−As multiple primary tumors in a single patient−As multiple types in a single patient−In more than one blood relative (same type)−Over several generations (same type)



Definitions

• Familial Cancero Clustering of relatively common cancers within

a biological familyo Most likely due to genetic change(s) which

have low penetrance (have a lower likelihood of causing cancer over an individual’s lifetime)

• Sporadic Cancero Cancer that occurs in an individual with no

associated genetic predisposition for ito Cancer that occurs in the general population



What do I know about community practice?

• Molecular Genetic Pathology fellowship

• Private Practice for 14 Monthso Large metropolitan hospital systemo General surgical pathology, cytopathology,

hematopathologyo Lots and lots of cancer, common and

uncommon

• Different perspective based on experience



Why should a generalist pathologist know something about genetics?

• Pathologists in community / general practice are holding the front lines of care

• Pathologists review previous case historieso May be first to recognize multiple tumor types in

a single patient

• Clinicians may lack access to all pathology reports

• Patients may be unaware ofo Their tumor history (exact names)o Significance of reporting family cancer history




• Patientso Earlier diagnosis of an HCS can lead to

−Earlier preventive measures for – The patient– The patient’s affected family members

−Justification for more screening outside of general recommendations

−Earlier family planning




• Bottom lineo Value-added service to physicians and patients


College of American Pathologists© 2011 College of American Pathologists. All rights reserved. 16

Aren’t hereditary cancer syndromes rare?


• 1.6 Million new cancers will be diagnosed in the US in 2011

• For a population of 500,000 people, this translates to o 2750 new cancer cases overall

−275 cancers from patients with HCS−550 cancers from patients with familial

cancer


Putting this in perspective


• I saw 3 – 5 cases per year that were suspicious for HCSo 8 person practice 24 – 40 cases per yearo Effective population base of 600,000

• HCS cancers are far more prevalent than we think

• There are a lot of patients with HCS who are going undetected


Putting it in perspective


• Recognition of a potential HCS

• Communication of risk for HCS


What are the barriers to HCS diagnosis?


What are the barriers to recognizing an HCS?

• Most pathologists (regardless of practice type)o Have not received a lot of education in

geneticso Are not familiar with genetic issueso Uncomfortable providing information on

genetic conditions or risk −To other physicians−To patients



What are the barriers to recognizing an HCS?

• Compounding the issue…

• Most community / private practices o Do not have molecular / genetic labso Have little exposure to genetics o No molecular genetic pathologist on staffo Are not familiar with local genetics resources



What are the barriers to communicating risk for HCS?

• Assumption that the provider already…o Has confirmation about patient’s HCS statuso Is working the patient up for an HCS

• Risk not confirmationo Pathologists like being definitive

−Especially if it is going into the reporto Potentially unnecessary stress on patient who

already has cancero Uncertainty as to how patient’s insurance

provider will handle this information



What are the barriers to communicating risk for HCS?

• Physicians in general are also not well educated on genetic issues o May not know what to do with the information

you give them without help


College of American Pathologists© 2011 College of American Pathologists. All rights reserved. 24

Let’s tackle some barriers…


Recognizing a potential HCS

• You get a caseo Check demographics (age, gender, etc.)o Check pathology history for anything unusual

(benign or malignant)




• General Red flags


Question Red Flag Answer

Is the patient younger than you would expect for this type of tumor?

Yes

Does the patient have a history of multiple primary tumors of the same type?

Yes

Does the patient have a history of multiple tumors of different types?

Yes



• If there are red flags, what do you do with this information?o There are hundreds of different types of HCSo No one can know them allo Many extremely rareo Some, however, are not…

−We will hit the high points−All are autosomal dominant

– 50% chance of offspring to have mutation




• Hereditary Non-Polyposis Colon Cancer (HNPCC)o mismatch repair genes (MLH1, MSH2, MSH6, PMS2)

o 1 in 400 people, 90% penetranto You should be concerned when…

−Modestly early-onset malignancies −Colorectal carcinoma (5% of all colon

cancers)−Combined with endometrial, urothelial and

other cancerso Primary Prevention increased surveillance




• Hereditary Breast and Ovarian Cancero BRCA1 and BRCA2o 1 in 500 to 1000 people, up to 85%

penetranto You should be concerned when…

−Early onset breast cancer (< 50 yo)−Any breast cancer with an ovarian cancer−Multiple primary breast malignancies−Any male breast cancer

o Primary prevention early surgical intervention, increased surveillance




• Neurofibromatosis Type 1o NF1o 1 in 3000 people, 100% penetranto You should be concerned when…

−Multiple cutaneous neuromas−Plexiform neurofibromas−Lisch nodules (iris hamartomas)

o Primary prevention surveillance for other lesions, particularly malignant peripheral nerve sheath tumors




• Familial Adenomatous Polyposis (FAP)o APCo 1 in 5000 to 10,000 people, 100% penetranto You should be concerned when…

−Abnormally high number of colon polyps– Attenuated FAP, Gardner syndrome

−Early onset colon polyps and cancero Primary prevention colectomy

recommended when > 20-30 polyps detected




• Multiple Endocrine Neoplasia (MEN) Type 2o RET proto-oncogeneo 1 in 30,000 people, eventually 100% penetranto You should be concerned when…

−Any patient has medullary thyroid carcinoma (MTC) regardless of family history

– 25% will have MEN2A or MEN2B– Children get very early onset MTC

o Primary prevention early thyroidectomy when diagnosis confirmed for all affected family members




• Von Hippel-Lindau (VHL)o VHL o 1 in 36,000 people, 90-95% penetranto You should be concerned when…

−Hemangioblastomas of eye/brain with renal cell carcinoma, pheochromocytoma, etc.

−(Any pheochromocytoma – 25% associated with a genetic disorder)

o Primary prevention Increased screening (eyes, blood pressure, urine catecholamines, abdominal ultrasound beginning at age 16)



Communicating an HCS

• I think this patient has an HCS. Now what do I do?

• Understanding genetic discriminationo http://www.genome.gov/10002328o Genetic Information Nondiscrimination Act

(GINA) – May 21, 2008−Prevents insurers and employers from

discriminating based on genetic information−Still a lot of bad behavior out there−Need for caution




• Suggested plan - Being proactive saves timeo See my previous CAP webinar on Clinical

Requests for Molecular Tests (http://www.cap.org/apps/docs/membership/transformation/new/mole_test.pdf)−Assign someone in your group to get extra

training in molecular genetics−Find your local genetic counseling services

and have them on file




• Before you call…o Determine which HCS(s) are possible for caseo Check previous history to see if provider on

previous tumors is the same or in same practice




• Call the patient’s providero Do they already know patient has an HCS?o Are they aware of previous tumor history?o If the answer to the above questions is “no”

−Discuss why you think the patient may have an HCS

−Does the provider know where to send the patient to get genetic counseling? If not, tell them.



Importance of genetic counseling

• Patient should see genetic counselor PRIOR to testingo Non-paternityo Possibility of passing to biological offspringo Resources for supporto Testing childreno Pre-symptomatic testing

• Patients may decide not to get testedo That is their choice




• Do you put your suspicions into the pathology report?

• Depends on who you talk to




• Here’s what I do (conservative):o In the report’s comment

−“Discussed concerns about this patient and his/her age and/or history of <list other tumors here> with …”

−I do not mention anything about an HCS




• Here’s what I do (conservative):o In my laboratory information system or other

laboratory-only communication record accessible by other members of my practice−Document the details of the discussion with

provider −Specifics on possible HCS and what was

recommended for this patient



By the end of this webinar, you should…

• Understand importance recognizing and communicating risk for hereditary cancer syndromes (HCS)

• Recognize warning signals for HCS in generalo Specific warning signals for common HCS

• Have a suggested plan for o Communicating risk to physicianso Documenting that communicationo Handling pathology reports



References

• Nice review on HCS (freely available)o Oncogene (2004) 23, 6445–6470

• Searchable database for more information - GeneReviewso http://www.ncbi.nlm.nih.gov/sites/GeneTests/review?db=genetests

• MD Anderson websiteo http://www.mdanderson.org/patient-and-cancer-information/cancer-

information/cancer-topics/prevention-and-screening/hereditary-cancer-syndromes/index.html

• General information on cancer statistics in USo http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/

documents/document/acspc-029771.pdf

o http://www.cancer.gov



Next in the Series of Free PHC Webinars

• Validating Whole Slide Imaging Systems for Diagnostic Use in Pathology, Thursday, October 12th, 11:00-12 pm CTo Liron Pantanowitz MD, FCAP

• Go to www.cap.org/institute For All Upcoming Webinars!

• Past Webinars Available Now Online at www.cap.org/instituteo Next-Generation Sequencing for the Clinical Laboratoryo Accountable Care Organizationso Whole Genome Analysis as a Universal Diagnostic

o How to Build and Fund a Financially Viable Molecular Lab

o Cancer: The Critical Role of Pathology

o Molecular Markers in Breast Cancer

o Bethesda System: Integrating Cytology and HPV Molecular Testing



CAP Learning – New Molecular Pathology CME Activities • Two, new online courses, both offer .5 CME

o Molecular Testing for AML Cases- Recognize molecular oncology knowledge and skills required of pathologists that can

mitigate problems and enhance patient care with respect to specimen handling- Realize the effects that appropriate specimen handling and communication throughout all

stages of diagnosis have in enhancing patient care- Reflect on your own knowledge and skills in specimen handling and patient care, and

identify what can help you and your practice be more effective in these areas of molecular oncology

o BRAF Mutation Testing in Melanoma- Follow quality assurance policies and procedures to ensure adequate sample collection

and proper handling techniques for molecular oncology tests- Use appropriate result reporting principles for incorporating molecular test results into

surgical pathology reports

• Unique Course Design o Models critical molecular oncology competencies – knowledge, skills and behaviors – and

reinforces key messages through knowledge checks, discussions and self-reflection. o Desired performance behaviors are modeled by characters in the story, which demonstrate a

highly diversified view of patient/pathologist interactions with respect to molecular oncology.

• Developed by members of the CAP Molecular Oncology committee

• Pricing: $25.00 member / $50.00 non-member

45

© 2011 College of American Pathologists. All rights reserved. This document is confidential and may not to be reproduced or distributed without permission from CAP Learning.

NewNew


CAP Learning – Other Molecular Pathology CME Activities

46

© 2011 College of American Pathologists. All rights reserved. This document is confidential and may not to be reproduced or distributed without permission from CAP Learning.

Course Learning ObjectivesMolecular Pathology: An Introduction to DNA Technology and Diagnostic Applications (SAM eligible)CME/SAM – 2.0

Identify potential application of molecular pathologyDescribe the chemical structure and properties of DNA and RNAExplain the different types of genetic variationsIdentify diagnostic techniques in molecular pathology

Archives Applied: KRAS (SAM eligible)CME/SAM – 1.0

Identify whether anti-EGFR therapy is an appropriate treatment method for a patient caseDescribe advantages and limitations of specific KRAS mutation testing methodsIdentify the appropriate elements to include in the report for a patient caseDescribe the current role of KRAS mutation testing for management of patients with metastatic colorectal cancer

Archives Applied: Molecular Test Validation (SAM eligible)CME/SAM = 1.0

Identify the appropriate:-test parameters for an analytic quantitative or qualitative test-clinical performance characteristics for test validation-performance characteristics for a quantitative or qualitative test-elements to include in test validation documentationIdentify pre-validation considerations for a proposed molecular pathology test

Archives Applied: Molecular Diagnostics of Soft Tissue Tumors (SAM eligible)CME/SAM = 1.0

Recognize which genetic alterations seen in soft tissue tumors are amenable to molecular diagnostics using routine clinical genetic approachesDescribe characteristics of chromosomal translocations in soft tissue sarcomasIdentify the advantages and limitations of conventional cytogenetic analysis for soft tissue tumorsIdentify approaches for assessing inactivation of a tumor suppressor gene, for example the SMARCB (INI1) in soft tissue tumorsIdentify the advantages and limitations of molecular cytogenetic analysis for soft tissue tumors


To learn more…

47

© 2011 College of American Pathologists. All rights reserved. This document is confidential and may not to be reproduced or distributed without written permission from CAP Learning.

• For more details and to register for Molecular Pathology educational offerings, see the Anatomic Pathology, Archives Applied and Self Assessment Modules (SAM) sections of the Education web page


CAP Events of Interest

• Don’t Forget to Register for CAP’11 – THE Pathologists’ Meeting – September 11 – 14, 2011 held at the Gaylord Texan in Grapevine, Texas!

–Go to www.cap.org/CAP11 or call 1-800-967-4548. International attendees please call 1-847-996-5891.


For more information go to www.cap.org/CAP11


Tuesday, Sept 13th:

TP120 Breakfast Workshop – Hot Topics in Pathology: What Every Community Pathologist Should Know About Clinical Requests for Molecular Tests (6:30-7:45 am)Faculty--Samuel K. Caughron, MD, FCAP

Frederick L. Kiechle, MD, PhD, FCAP Michael S. Brown, MD, FCAP

ST109 Companion Diagnostics for Targeted Therapy in Cancer (2:00-5:30 pm)Faculty--Sanja Dacic, MD, PhD, FCAP David Hicks, MD, FCAP Jeffrey Kant, MD, PhD, FCAP

Wednesday, Sept 14th:

ST110 Direct-to-Consumer Genetic Testing: Staying Ahead of Patients in This Current Trend (8:00-9:00 am)Faculty--Nazneen Aziz, PhD

Elizabeth A. Mansfield, PhD

ST111 What’s in It for Me? Using Technology to Become a Diagnostic Hero (8:00-11:30 am)Faculty--Kenneth J. Bloom, MD, FCAP

John W. Turner, MD, FCAP


For more information go to www.cap.org/CAP11

Tuesday, Sept 13th:

FP100 The Best of Futurescape (9:00-11:30 am) Faculty—Wayne W. Grody, MD, PhD, FCAP Michael Laposata, MD, PhD, FCAP Cindy L. Vnencak-Jones, PhD

Wednesday, Sept 14th:

ST112 CAP Foundation Keitges Program on Medical Ethics: Genetic Testing in Late Onset Autosomal Dominant Disorders (1:00-3:00 pm)Faculty—Kimberly A. Quaid, PhD

Gail H. Vance, MD, FCAP


Documents

College of American Pathologists Welcome to the PHC Webinar Series © 2010 College of American Pathologists. All rights reserved. 1 This lecture on “The