Table Of ContentPharmacogenetics
of Breast Cancer
TRANSLATIONAL MEDICINE SERIES
1. Prostate Cancer: Translational and Emerging Therapies, edited by
NancyA. Dawson and W. Kevin Kelly
2. Breast Cancer: Translational Therapeutic Strategies, editedbyGary
Lyman and Harold Burstein
3. Lung Cancer: Translational and Emerging Therapies, edited by
Kishan J. Pandya, Julie R. Brahmer, and Manuel Hidalgo
4. Multiple Myeloma: Translational and Emerging Therapies, editedby
Kenneth C. Anderson and Irene Ghobrial
5. Cancer Supportive Care: Advances in Therapeutic Strategies,
editedby Gary H. Lyman andJeffrey Crawford
6. Cancer Vaccines: Challenges and Opportunities in Translation,
edited byAdrian Bot and Mihail Obrocea
7. Pharmacogenetics of Breast Cancer: Towards the Individualization
of Therapy, editedby Brian Leyland-Jones
Pharmacogenetics
of Breast Cancer
Towards the
Individualization of Therapy
Edited by
Brian Leyland-Jones
Winship Cancer Institute
Emory University School of Medicine
Atlanta, Georgia, USA
Boca Raton London New York
CRC Press is an imprint of the
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First published 2008 by Infonna Healthcare
Published 2018 by CRC Press
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ISBN 13: 978-1-4200-5293-0 (hbk)
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Library of Congress Cataloging-in-Publication Data
Pharmacogenetics of breast cancer : towards the individualization of therapy/ edited by
Brian Leyland-Jones.
p. ; cm. - (Translational medicine series ; 7)
Includes bibliographical references and index.
ISBN-13: 978-1-4200-5293-0 (hardcover: alk. paper)
ISBN-JO: 1-4200-5293-4 (hardcover: alk. paper)
I. Breast-Cancer-Genetic aspects. 2. Breast-Cancer-Chemotherapy.
3. Pharmacogenetics. I. Leyland-Jones, Brian. II. Series.
[DNLM: I. Breast Neoplasms-genetics. 2. Breast Neoplasms-drug therapy.
WP 870 P536 2008]
RC280.B8P43 2008
616.99'449--<lc22
2008001013
VJSit the Tuylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
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Preface
Iwritethisprefaceon Christmas Day, 2007, in CostaRica. Christmas is always a
special time for me, since my parents were married on Christmas Day sixty
nine years ago. It is almost unimaginable to think how far we have progressed
since 1938. My parents were married in the year before the Second World
War. The nitrogen mustards, from which arose the first chemotherapies, were
developed during the war. Iwas fortunate during my training at Sloan-Kettering
to work in the laboratories of Fred Phillips, Joe Burchenal, and Jack Fox, which
conducted some of the pivotal work on these compounds. Indeed, the first task
force for childhood leukemia was set up in Washington in the year of my birth.
However, we all have to remember how slowly treatments are disseminated to
the community; I can remember, as a child, my next-door neighborhaving aleg
amputated for metastatic lung cancer since no other treatments were accessible
locally!
The rest is history, but again it is difficult to believe that the Nobel Prize
for the discovery of the cellular origin of retroviral oncogenes was awarded to
Bishop and Varmus only in 1989.
Now we face the challenge of too few patients eligible forclinical trials to
adequately test the myriad of targeted therapies available as well as the avail
ability of high-quality starting material with associated clinical and phenotypic
data. Various platforms are available for the identification of biomarkers: early
technologies have focused on reverse transcriptase polymerase chain reaction
and expression arrays. Now single nucleotidepolymorphisms, array comparative
genomic hybridization, methylation signatures, microRNAs, and proteomics are
increasingly included in biomarker profiling; nanotechnology, molecular imag
ing, and the use of circulating tumor cells are advancing at a tremendous pace.
By the time this book is released, the specimen collection guidelines for breast
cancer, representing a joint effort between the North American cooperative
11/
Preface
IV
groups and those comprising the Breast International Group (BIG), will have
been published and be available for open Web access. We have attempted to
cover the breadth of these diverse areas in this book.
I amespeciallyproudofthree aspectsofthe book. Thefirstisthe timeliness,
as so many new approaches to individualization of therapy have emerged, and
when two very large randomized trials are aggressively accruing on the basis of
Oncotype and mammoprint. Second, the diversity ofthe topics covered, ranging
from pathology, tissue handling, DNA-, expression-, and epigenetic-based
approaches, nanotechnology, stem cells, circulating tumor cells, endocrine, and
chemotherapeutic through to pharmacologic aspects and the key pivotal trials.
Third, I am proud that so many of my most distinguished friends and colleagues
from around the world have been so generous with their time and devotion to
make this book outstanding.
Finally, in writing this preface from one of the most beautiful places on
earth, Iam deeply reminded ofthe disparities in access to healthcare. We are all
immensely grateful that my friends and colleagues John Seffrin and Otis
Brawley at the American Cancer Society have been leaders in bringing this
critical issue to the forefront of public consciousness, but we must never fail to
rememberthat severe disparities in access to care remain, not only in the United
States but globally. Individualized therapy is not only meant to direct therapy to
those who will benefit most but also intended to reduce waste and improve cure
rates dramatically, so that this therapy is available to all who suffer. Let us, the
privileged, never move our focus from the most disadvantaged in our world and
aim at using individualized therapy as a means to make our most sophisticated
treatment available and affordable to all.
Brian Leyland-Jones, M.D., Ph.D.
Acknowledgments
Many thanks are owed on a personal level, especially to all my friends and
coauthors who have been immensely generous in dedicating their nonexistent
spare moments to contributing the various chapters. I am deeply grateful to the
publisher, Informa Healthcare, who not only had the insight to partner with
me on this book but also had the patience to wait for the “nonexistent spare
moments” of the contributing authors to materialize. I must also profoundly
apologize to several colleagues who were approached early on to contribute
chaptersbutwho were unabletobecause ofthe originaltime lines andnow must
be frustrated because the time lines were forced to be extended considerably.
Most especially, I must thank my dear, dearcolleague, Dr. Brian R. Smith, who
was relentless in organization, follow-up, and advice, a man whose wisdom I
rely upon atso manycriticalmoments andto whose structuredapproachIaspire.
Iam deeply, deeply grateful to Charles Bronfman, whose chairin the memory of
his dear sister, Minda, sustained me over the past 17 years and who now has
inspirationally established his own Institute of Personalized Cancer Therapy in
New York. I amgrateful also totheFlanders family whohave shown me a depth
of kindness, support, and friendship that is without equal. Finally, I am humbled
by my research and clinical colleagues who instruct and guide me constantly,
and especiallybyeach andeverypatientwhoinspiresus andteaches, ineach and
every encounter, just how personalized breast cancer therapy really is.
v
Contents
Preface ..................... iii
Acknowledgments .... v
Contributors ................ xi
1. Pharmacogenetics ofBreast Cancer: Toward the Individualization
of Therapy ........................................................................................... 1
Jenny C. Chang, Susan G. Hilsenbeck, and Suzanne A. W. Fuqua
2. Pharmacology, Pharmacogenetics, and Pharmacoepidemiology:
Three P’s of Individualized Therapy ............................................ 11
Shaheenah Dawood
3. Role of Genetic Variability in Breast Cancer Treatment
Outcomes ........................................................................................... 25
Kandace L. Amend, Ji-Yeob Choi, and Christine B. Ambrosone
4. The Role ofEpigenetics in Breast Cancer: Implications for
Diagnosis, Prognosis, and Treatment ............................................ 45
Amy M. Dworkin, Tim H.-M. Huang, and Amanda E. Toland
5. Comparative Genomic Hybridization and Copy Number
Abnormalities in Breast Cancer ...................................................... 61
Nicholas Wang and Joe Gray
vii
