Cancer principles & practice of oncology: handbook of clinical cancer genetics

240 Pages·2013·14.686 MB·English

by  Matloff, Ellen T

CANCER
Principles & Practice
of Oncology:
Handbook of
Clinical Cancer
Genetics
Ellen T. Matloff, MS
Research Scientist, Department of Genetics
Director, Cancer Genetic Counseling
Yale Cancer Center
New Haven, Connecticut
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Chapters 2–15 of this book were originally published in The Cancer Journal: The Journal of Principles and Practice
of Oncology Volume 18, Number 4, July/August 2012, edited by Vincent T. DeVita, Jr., Theodore S. Lawrence, and
Steven A. Rosenberg, and published by Lippincott Williams & Wilkins.
Chapter 1 was originally published in DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of
Oncology, 9th edition, edited by Vincent T. DeVita, Jr., Theodore S. Lawrence, and Steven A. Rosenberg, and
published by Lippincott Williams & Wilkins, copyright 2011.
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ISBN 978-1-4511-9098-4
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Contents
Preface v
Contributors vii
Section I Introduction
1 Cancer Genetic Counseling 1
Ellen T. Matloff • Danielle C. Bonadies
Section II Current Topics in Cancer Genetic Counseling
2 Whole-genome and Whole-exome Sequencing in Hereditary
Cancer: Impact on Genetic Testing and Counseling 23
Julianne M. O’Daniel • Kristy Lee
3 Direct-to-consumer Personal Genome Testing and
Cancer Risk Prediction 35
Cecelia A. Bellcross • Patricia Z. Page • Dana Meaney-Delman
4 Adverse Events in Cancer Genetic Testing: Medical, Ethical,
Legal, and Financial Implications 57
Karina L. Brierley • Erica Blouch • Whitney Cogswell • Jeanne P. Homer •
Debbie Pencarinha • Christine L. Stanislaw • Ellen T. Matloff
Section III Genetic Testing by Disease Site
5 Genetic Testing by Cancer Site: Breast 71
Kristen M. Shannon • Anu Chittenden
6 Genetic Testing by Cancer Site: Ovary 93
Scott M. Weissman • Shelly M. Weiss • Anna C. Newlin
7 Genetic Testing by Cancer Site: Colon (Polyposis Syndromes) 111
Kory W. Jasperson
8 Genetic Testing by Cancer Site: Colon (Nonpolyposis
Syndromes) 125
Leigha Senter
9 Genetic Testing by Cancer Site: Uterus 133
Molly S. Daniels
10 Genetic Testing by Cancer Site: Urinary Tract 143
Gayun Chan-Smutko
iii
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iv Contents
11 Genetic Testing by Cancer Site: Pancreas 157
Jennifer E. Axilbund • Elizabeth A. Wiley
12 Genetic Testing by Cancer Site: Stomach 167
Nicki Chun • James M. Ford
13 Genetic Testing by Cancer Site: Endocrine System 187
Robert Pilarski • Rebecca Nagy
14 Genetic Testing by Cancer Site: Skin 203
Michele Gabree • Meredith Seidel
Gene Index 225
Syndrome Index 227
Term Index 229
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Preface
e stand at an interesting crossroads in the field of cancer genetic counseling
W
and testing. Less than two decades ago, clinical testing for hereditary cancer
syndromes was a rare event reserved for infrequently observed syndromes
that a clinician might see once or twice in a lifetime. A small handful of specialized
laboratories performed such testing and it was not unusual to send a sample to an-
other country for processing as the options were limited and expertise sparse.
All of that changed early in 1996 when clinical testing became available for
mutations within BRCA1 and BRCA2. Those of us on the front lines were be-
sieged with phone calls from patients wanting the test, reporters enquiring what
we would do with the information, and medical colleagues questioning if and
how these data would be useful. I remember lecturing to a small group of re-
search clinicians at my institution soon after BRCA testing became available and
discussing the option of prophylactic mastectomy and oophorectomy for women
who tested BRCA positive. I found myself dodging angry accusations of “mutilat-
ing” women’s bodies based on “genetic fortune telling,” and opening Pandora’s
box, psychologically and emotionally ruining women who would then be unin-
surable and societal castaways. Let’s just say that cancer genetic testing was not
welcomed with open arms by everyone.
The truth is that we didn’t know how testing would unfold. Those of us providing
counseling and testing had no information on how real-life patients outside of care-
fully proctored research protocols would handle this information. Would they be for-
ever depressed? Would their anxiety levels make it impossible for them to function?
Could this possibly make patients suicidal? We didn’t know and we were worried. But,
once testing hit the marketplace, there was no holding back the surge.
We were also concerned about insurability. Would patients who tested positive
lose their health insurance coverage and, therefore, the ability to have the careful sur-
veillance and expensive risk reduction surgeries we were recommending? If employ-
ers learned this information, would patients be passed up for promotions or even lose
their jobs for fear that they would cost their companies too much money?
And, speaking of the surveillance and risk reduction surgeries we were offering,
would they even work? I had multiple “academic conversations” with physicians at
my institution who questioned whether prophylactic oophorectomy would ade-
quately reduce the risk of ovarian cancer in BRCA carriers. Perhaps mutation carriers
would then be at high risk to develop primary cancers in other locations? Although
we thought that unlikely (and luckily, we were right), we had no long-term data to
support this, or any, of our hypotheses.
Much has changed since 1996. We now have data demonstrating that there are
no serious long-term psychological and emotional sequelae associated with genetic
testing. Our fears regarding health insurance discrimination have not played out, per-
haps in part to aggressive and supportive legislation via HIPAA and GINA protecting
v
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vi Preface
patients from genetic discrimination. Also, the employment and social repercussions
have not been reported as major issues.
The surveillance and risk reduction surgeries we recommended, albeit far from
perfect, have proven to be extremely effective in reducing cancer risk in carriers.
While we have fewer data regarding chemoprevention in these populations, we are
optimistic that these drugs may also reduce risk in these high risk families.
Interestingly, the issues that have generated the greatest dangers in the field of
genetic counseling and testing are those we did not anticipate. Namely, how gene
patents would create corporate monopolies and thwart competition, research and
data-sharing in the field, and how this would impact pricing, access, and market-
ing of genetic testing. As you will read in Brierley et al.’s chapter, in part because of
aggressive marketing of patented testing to clinicians without expertise in genetic
counseling, there have been serious, adverse clinical outcomes for patients and their
well-meaning physicians who ordered genetic testing in lieu of adequate counseling
by a certified provider. And, as you will read in the thorough “Disease site” chapters,
genetic testing encompasses many more genes than simply BRCA and Lynch syn-
drome genes. Risk assessment for these syndromes is not as simple as punching a few
details into a risk calculator or taking just a family history of cancer; there are varied
cancerous and noncancerous findings that impact the chance that a syndrome is pres-
ent and influence what test should be ordered.
At this critical crossroads in our field, we see that targeted testing for one or two
disease genes at a time may soon be coming to an end. Panels of disease genes and
whole-exome sequencing, as you will read in O’Daniel and Lee’s chapter, may soon
become less expensive and much more informative than single-gene testing. The
amount and complexity of data these new tests will yield is staggering. The amount
of ambiguity in test results may increase by hundred-fold, making genetic counseling
and result interpretation substantially more challenging—even for those of us who
are experts in this field. And yet, ironically, complex genetic testing is now being mar-
keted directly to consumers. (See Bellcross’s chapter).
And so, the journey picks up speed and continues. Many thanks to my colleagues,
some of the brightest minds in this field, who have donated their time and expertise
to write the elegant and thorough chapters you will now have the opportunity to read.
Ellen T. Matloff, MS
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Contributors
Jennifer E. Axilbund, MS, CGC James M. Ford, MD
Cancer Risk Assessment Program Associate Professor of Medicine and
The Johns Hopkins Hospital Genetics
Baltimore, Maryland Stanford University School of Medicine
Division of Oncology
Cecelia A. Bellcross, PhD, MS, CGC
Stanford University School of Medicine
Assistant Professor
Stanford, California
Director, Genetic Counseling Training
Program Michele J. Gabree, MS
Department of Human Genetics Certified Genetic Counselor
Emory University School of Medicine Center for Cancer Risk Assessment
Atlanta, Georgia Massachusetts General Hospital
Boston, Massachusetts
Erica Blouch, MS, CGC
Center for Cancer Risk Assessment Jeanne P. Homer, MS, CGC
Massachusetts General Hospital Hoag Hospital
Boston, Massachusetts Newport Beach, California
Karina L. Brierley, MS, CGC
Kory W. Jasperson, MS, CGC
Senior Genetic Counselor
Huntsman Cancer Institute
Yale Cancer Center
Salt Lake City, Utah
New Haven, Connecticut
Kristy Lee, MS
Gayun Chan-Smutko, MS, CGC
Certified Genetic Counselor
Massachusetts General Hospital Cancer Center
University of North Carolina Cancer &
Boston, Massachusetts
Adult Program
Anu Chittenden, CGC Chapel Hill, North Carolina
Genetic Counselor
Ellen T. Matloff, MS
Dana-Farber Cancer Institute
Research Scientist, Department of
Boston, Massachusetts
Genetics
Nicolette M. Chun, MS, LCGC Director, Cancer Genetic Counseling
Clinical Assistant Professor of Pediatrics/ Yale Cancer Center
Genetics New Haven, Connecticut
Stanford Cancer Genetics Clinic
Dana Meaney-Delman, MS, CGC
Stanford, California
Department of Obstetrics and
Whitney Cogswell, MS, CGC Gynecology
Medical Center of Central Georgia Emory University School of Medicine
Macon, Georgia Atlanta, Georgia
Molly S. Daniels, MS, CGC Rebecca Nagy, MS, CGC
University of Texas, MD Anderson Cancer Clinical Cancer Genetics Program
Center The Ohio State University
Houston, Texas Columbus, Ohio
vviiii
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viii Contributors
Anna Newlin, MS, CGC Kristen Mahoney Shannon, MS, CGC
Center for Medical Genetics Program Manager/Senior Genetic
NorthShore University HealthSystem Counselor
Evanston, Illinois Center for Cancer Risk Assessment
Massachusetts General Hospital Cancer
Julianne M. O’Daniel, MS
Center
Illumina, Inc.
Boston, Massachusetts
San Diego, California
Christine L. Stanislaw, MS, CGC
Tricia Z. Page, MS, CGC
Division of Medical Genetics
Director, Genetic Counseling Services
Emory University
Instructor
Decatur, Georgia
Emory University
Decatur, Georgia Shelly Weiss, MS, CGC
Certified Genetic Counselor
Debbie Pencarinha
Evanston, Illinois
Kingsport Hematology and Oncology
Wellmont Cancer Center Scott M. Weissman, MS, LGC
Kingsport, Tennessee Licensed Genetic Counselor
Center for Medical Genetics
Robert Pilarski, MS, CGC, MSW, LSW
Evanston, Illinois
Clinical Cancer Genetics Program
The Ohio State University Elizabeth A. Wiley, MS
Columbus, Ohio Department of Oncology
The Johns Hopkins University School of
Meredith Seidel, MS, CGC
Medicine
Center for Cancer Risk Assessment
Baltimore, Maryland
Massachusetts General Hospital
Boston, Massachusetts
Leigha Senter, MS, CGC
Assistant Professor
Human Genetics
The Ohio State University
Columbus, Ohio
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Cancer Genetic
1
Counseling
Ellen T. Matloff and Danielle C. Bonadies
n the past 15 years, clinically based genetic testing has evolved from an
I
uncommon analysis ordered for the rare hereditary cancer family to a widely
available tool ordered on a routine basis to assist in surgical decision mak-
ing, chemoprevention, and surveillance of the patient with cancer, as well as manage-
ment of the entire family. The evolution of this field has created a need for accurate
cancer genetic counseling and risk assessment. Extensive coverage of this topic by the
media and widespread advertising by commercial testing laboratories have further
fueled the demand for counseling and testing.
Cancer genetic counseling is a communication process between a health care
professional and an individual concerning cancer occurrence and risk in his or her
family.1 The process, which may include the entire family through a blend of genetic,
medical, and psychosocial assessment and intervention, has been described as a
bridge between the fields of traditional oncology and genetic counseling.1
The goals of this process include providing the client with an assessment of indi-
vidual cancer risk, while offering the emotional support needed to understand and
cope with this information. It also involves deciphering whether the cancers in a fam-
ily are likely to be caused by a mutation in a cancer gene and, if so, which one. There
are >30 hereditary cancer syndromes, many of which can be caused by mutations in
different genes. Therefore, testing for these syndromes can be complicated. Advertise-
ments by genetic testing companies bill genetic testing as a simple process that can
be carried out by health care professionals with no training in this area; however,
there are many genes involved in cancer, the interpretation of the test results is often
complicated, the risk of result misinterpretation is great and associated with poten-
tial liability, and the emotional and psychological ramifications for the patient and
family can be powerful. A few hours of training by a company generating a profit
from the sale of these tests does not adequately prepare providers to offer their own
genetic counseling and testing services.2 Furthermore, the delegation of genetic test-
ing responsibilities to office staff is alarming3 and likely presents a huge liability for
these ordering physicians, their practices, and their institutions. Providers should pro-
ceed with caution before taking on the role of primary genetic counselor for their patients.
1
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2 Principles and Practice of Oncology: Handbook of Clinical Cancer Genetics
Counseling about hereditary cancers differs from “traditional” genetic counseling in
several ways. Clients seeking cancer genetic counseling are rarely concerned with repro-
ductive decisions that are often the primary focus in traditional genetic counseling, but
are instead seeking information about their own and other relatives’ chances of devel-
oping cancer.1 In addition, the risks given are not absolute but change over time as the
family and personal history changes and the patient ages. The risk reduction options
available are often radical (e.g., chemoprevention or prophylactic surgery), and are not
appropriate for every patient at every age. The surveillance and management plan must
be tailored to the patient’s age, childbearing status, menopausal status, risk category,
ease of screening, and personal preferences, and will likely change over time with the
patient. The ultimate goal of cancer genetic counseling is to help the patient reach the
decision best suited to her personal situation, needs, and circumstances.
There are now a significant number of referral centers across the country spe-
cializing in cancer genetic counseling and the numbers are growing. However, some
experts insist that the only way to keep up with the overwhelming demand for coun-
seling will be to educate more physicians and nurses in cancer genetics. The feasibility
of adding another specialized and time-consuming task to the clinical burden of these
professionals is questionable, particularly with average patient encounters of 19.5 and
21.6 minutes for general practitioners and gynecologists, respectively.4,5 A more prac-
tical goal may be to better educate primary care providers in the area of generalized
risk assessment so that they can screen their patient populations for individuals at
TABLE
How to Find a Genetic Counselor for your Patient
1.1
Gene tests
www.ncbi.nlm.nih.gov/sites/GeneTests/clinic—(206) 616–4089
[email protected]
A listing of US and international genetics clinics providing evaluation and genetic
counseling
Informed medical decisions
www.informeddna.com–(800) 975–4819
Nationwide network of independent genetic counselors that use telephone and
internet technology to bring genetic counseling to patients and providers. Covered by
many insurance companies.
National society of genetic counselors
www.nsgc.org—click “Find a Counselor” button—(312) 321–6834
For a listing of genetic counselors in your area who specialize in cancer.
NCI cancer genetics services directory
www.cancer.gov/cancertopics/genetics/directory—(800) 4-CANCER
A free service designed to locate providers of cancer risk counseling and testing services.
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