Cancer, 1st Edition

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This book is dedicated to the next generation of scientists and doctors whose
work will provide hope for the future of all those touched by cancer.
It’s the little pebbles that make a path.
—Mary Claire King
 Contents

Series Foreword ix
Preface xi
Acknowledgments xiii
Introduction xv
Chapter 1. Know the Enemy: Understanding Cancer 1
Chapter 2. Detective Work: Making the Diagnosis of Cancer 65
Chapter 3. Plan of Attack: Cancer Treatments 77
Chapter 4. Maintaining Quality of Life after a Cancer Diagnosis 101
Chapter 5. When Cancer Treatments Don’t Work 111
Chapter 6. Hope for the Future 117
Appendix A. How You Can Pursue a Career in Science or Medicine 127
Appendix B. Cancer Timeline 135
Appendix C. Internet Resources 143
viii Contents

Glossary 145
References 155
Index 171
 Series Foreword

E
very disease has a story to tell: about how it started long ago and began to
disable or even take the lives of its innocent victims, about the way it
hurts us, and about how we are trying to stop it. In this Biographies of Dis-
ease series, the authors tell the stories of the diseases that we have come to know
and dread.
The stories of these diseases have all of the components that make for great
literature. There is incredible drama played out in real-life scenes from the past,
present, and future. You’ll read about how men and women of science stumbled
trying to save the lives of those they aimed to protect. Turn the pages and you’ll
also learn about the amazing success of those who fought for health and won,
often saving thousands of lives in the process.
If you don’t want to be a health professional or research scientist now, when
you finish this book you may think differently. The men and women in this book
are heroes who often risked their own lives to save or improve ours. This is the
biography of a disease, but it is also the story of real people who made incredible
sacrifices to stop it in its tracks.
Julie K. Silver, M.D.
Assistant Professor, Harvard Medical School
Department of Physical Medicine and Rehabilitation
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 Preface

A
s a young girl, I was introduced to cancer in a very personal way. My mother
and her best friend both developed breast cancer in their forties. My mother
survived her battle with cancer and is still thriving in her eighties, but her
friend, Violet, died shortly after being diagnosed. At the same time, I started accompa-
nying my father on his rounds as a surgeon at the hospital and have a searing memory of
seeing a man whose face was covered with skin cancers, a consequence of radiation
treatment for acne when he was a teenager. These experiences have formed the basis
for my lifelong interest in cancer research.
Susan E. Pories, M.D.

Cancer is a diagnosis that causes fear and confusion. However, as evidenced

by the examples above, cancer is really a family of diseases and the disease pro-
cess, causes, and prognosis can vary widely. This book introduces you to this vast
topic by starting with the history of cancer as well as seminal figures and discov-
eries on the path to today’s understanding of cancer. Chapter 1 will teach you
about the various causes of cancer and the principles of genetics. The impor-
tance of angiogenesis—the development of new capillaries—in the growth and
progression of cancer is discussed, and the various factors contributing to the
occurrence of cancer are explored. Chapter 2 explains the process of diagnosis,
xii Preface

and Chapter 3 introduces cancer treatments, including surgery, radiation,

chemotherapy, and targeted treatments such as hormonal therapy, immuno-
therapy, and antiangiogenesis agents. The dangers of unproven or alternative
treatments are also discussed. In Chapter 4, the growing field of psycho-
oncology and the importance of support from family and community are intro-
duced. Role models from the sports world show the inspiration of courage and
hope in the face of disease. In Chapter 5, the limits of cancer treatments are
explained with a discussion of drug resistance and an introduction to end of life
care. Finally, Chapter 6 discusses new frontiers in cancer research and preven-
tion and gives students an idea of how they can enter careers in medicine and
science. A comprehensive glossary of terms and a timeline of advances in cancer
research and treatment are provided.
As it is not possible to cover all of cancer in a volume of this size, we have
chosen to focus on illustrative examples and interesting stories that we hope will
intrigue and interest you. We hope to encourage and inspire you to learn more
and perhaps join us in medicine and science.
 Acknowledgments

W
e thank Dr. Julie Silver for the opportunity to work on this exciting
educational project. We are grateful to Kristin Johnson for her excel-
lent illustrations, Caitlin Welsh and Megan Lafferty for editing and
administrative support, and are most appreciative of the beautiful images pro-
vided by Dr. Pierre Sasson, Dr. Athos Bousvaros, Benny Lassen, and Dr. Brian
Organ.
Most of all, we thank our families Christopher, Louis, Gerard, Alexander, Athos,
and George with love and appreciation.
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 Introduction

I ignore all the doomsaying nonsense. I’m in a business where the odds of ever
earning a living are a zillion to one, so I know it can be done. I know the impos-
sible can become possible.
—Marcia Wallace

Wallace, an Emmy Award-winning actress, commenting on her husband’s

diagnosis of pancreatic cancer. People Magazine (March 2, 1992).

T
he word ‘‘malignant’’ comes from the Latin combination of ‘‘mal’’ mean-
ing ‘‘bad’’ and ‘‘nascor’’ meaning ‘‘to be born.’’ Malignant then literally
means ‘‘born to be bad.’’ This implies that cancer is inevitably pro-
grammed into cells and prevention is doomed to fail. Today we know that many
cancers are preventable and treatable with early diagnosis and proper care.
There are many common cancer myths that persist into modern times, such
as these: cancer is contagious, cancer is a death sentence, biopsy can make a
cancer spread, curses can cause cancer, cancer is God’s will, dying is preferable
to surgery, and air can cause cancer to grow (Pories, et al., 2006). Although we
have not yet won the ‘‘war against cancer’’ we have made immense progress
xvi Introduction

against this disease and move ever closer to the day when cancer is better under-
stood and can be managed as a chronic disease, much like infection or diabetes.
This book provides an introduction to the topic of cancer. We have not
attempted an encyclopedic approach but rather have chosen to focus on the
most common cancers in adults and some of the most interesting and seminal
advances in cancer research and treatment. Human interest stories are included
to help bring the study of scientific research to life. We have also tried to make
complicated scientific knowledge understandable. Even if you are not yet fully
interested and engaged in science, we hope that you might be inspired to enter
this important field. We also hope to empower you to educate your friends and
families about cancer prevention and treatment.
Understanding cancer is more important than ever because, according to the
World Health Report, cancer is predicted to become the leading cause of death
worldwide in the year 2010 (Boyle and Levin, 2008). The global burden of
cancer doubled between 1975 and 2000 and is expected to continue at an
unprecedented rate, redoubling by 2020 and tripling by 2030. Scientific research
along with educational and preventive strategies such as tobacco and alcohol
control, widespread screening, and improved access to care, has the exciting
potential to change this trajectory.
1
Know the Enemy:
Understanding Cancer

Science and everyday life cannot and should not be separated. Science, for me,
gives a partial explanation of life. In so far as it goes, it is based on fact, experi-
ence, and experiment . . .I agree that faith is essential to success in life. . .In my
view, all that is necessary for faith is the belief that by doing our best we shall
come nearer to success and that success in our aims (the improvement of the
lot of mankind, present and future) is worth attaining.
—Dr. Rosalind Franklin in a letter to Ellis Franklin, ca. summer 1940

WHAT DO CRABS HAVE TO DO WITH CANCER?

O
ne of the earliest written records of cancer is found in the Edwin Smith
surgical papyrus, an Egyptian textbook of medicine, thought to be writ-
ten in 1600 BCE (Breasted, 1930). Named for an American antiquities
dealer who bought the document, the Edwin Smith surgical papyrus is a collection
of writing about surgery and trauma. The papyrus contains one of the earliest
descriptions of breast cancer and states that there is no treatment for the disease.
In general, the Egyptians blamed cancers on the Gods (Hajdu, 2006). The pres-
ervation of mummies by the Egyptians allows modern scholars to study cancer in
antiquity (Weiss, 2000a).
2 Cancer

Hippocrates (460–370 BCE), the Greek physician who is considered the

father of medicine, believed that the body contained four humors or body fluids:
blood, phlegm, yellow bile, and black bile (Hajdu, 2004; Hajdu, 2006). He felt
that a balance of these fluids resulted in a state of health, while cancer was due
to an imbalance of the fluids with an excess of black bile. Hippocrates believed
that cancer was an imbalance between the black bile and the three bodily
humors—namely, blood, phlegm and yellow bile—and he attributed the origin
of cancer to natural causes. The black bile was not confined to the cancer but
was considered to flow throughout the body and carried the cancer throughout
the body. Hippocrates also noted the resemblance of a spreading cancer to a crab
with its claws extended and named it ‘‘karkinos,’’ the Greek work for crab
(Weiss, 2000b)
The Romans followed the teaching of Hippocrates. One of the most promi-
nent early Roman physicians was Galen (130–201 AC), whose books were pre-
served for centuries and who was the highest medical authority for more than a
thousand years (Todman, 2007). Galen viewed cancer much as Hippocrates
had, and his views set the pattern for cancer management for centuries.
At that time, doctors had little to offer in terms of treatment, and all cancer
was considered incurable. These doctors observed that cancer would usually
return after it was removed by surgery. Another well-known Roman physician
Aulus Cornelius Celsus (25 BCE–50 AC) described the progression or stages of
cancer and did not think it was curable: ‘‘After excision, even when a scar has
formed, none the less the disease has returned.’’ (Hajdu, 2006)
Little progress was made in the understanding of cancer or cancer treatment
during the Middle Ages. However, in the 1500s, Andreas Vesalius began to per-
form human dissections and document anatomy. Vesalius challenged the theory
of black bile as a cause of cancer, as his anatomic dissections did not find evi-
dence of black bile (Weiss, 2000b).

THE POWER OF OBSERVATION

The modern understanding of cancer began in the 1600s with the increasing
ability to study biology and how disease develops. William Harvey, in 1628, used
autopsy findings to help explain the circulation of blood through the heart and
body. He also experimented with transfusions from animals to humans (Graham,
1953).
Later in the 1600s, microscopes were introduced, allowing study of the body at
a much closer level. In 1665, Robert Hooke devised the first compound micro-
scope and published his book Micrographia, describing his observations (Gest,
2004). In 1673, Antony van Leeuwenhoek improved the microscope lens and
 Know the Enemy 3

was the first to observe single-celled creatures and blood cells. The earliest
microscopes were essentially composed of a magnifying glass that focused on a
specimen mounted on a sharp point that stuck up in front of the lens. The
microscope was tiny, about 3–4 inches in all and was held up to the examiner’s
eye. Tiny thumb screws were used to adjust the position of the specimen (Gest,
2004).
One of the most important advances was the recognition of the relationship
between disease and autopsy findings. In the 1700s, Giovanni Battista Morgagni,
professor of anatomy in University of Padua, Italy performed autopsies to better
understand the patient’s illness and published De Sedibus et Causis Morborum—
on the Seats and Causes of Disease, based on 700 case studies (Hill and Anderson,
1989).

IT’S ALL ABOUT CELLS

Another important step in understanding cancer was the demonstration in
the 1800s by Johannes Muller, a German pathologist, that cancer is made up of
cells. However, Muller thought that cancer cells arose from undifferentiated
cells, which he termed the ‘‘blastema,’’ and not from normal cells, a notion that
was later disproved (Hajdu, 2006; Shimkin, 1976).
A student of Muller’s, Rudolf Virchow, became known as the ‘‘Founder of
Cellular Pathology.’’ He studied cells through the microscope and noted: ‘‘Omnis
cellula e cellula,’’ meaning that all cells come from other cells and that disease
cells originate from normal body cells. He also recognized that lymph glands
near tumors were filled with cells similar in appearance to the cells of the tumor,
showing that the cancer cells were carried by the lymph system throughout the
body, causing spread of the cancer (Androutsos, 2004).
The knowledge about the cellular origin of cancer was soon applied clinically,
and in 1851, W. H. Walshe, an Englishman, was the first to describe the appear-
ance of malignant lung cancer cells in the sputum, seen through the microscope.
He realized that this could provide an important method of early diagnosis and
wrote, ‘‘if the cancer had softened, the microscopic characters of that product
may be found sometimes in sputa’’ (Beale, 1854, p. 234).

WE CAN DO BETTER THAN THE KITCHEN TABLE

The 19th century was a time of advances in many fields. New devices such as
bronchoscopes, gastroscopes, and cystoscopes allowed physicians to look directly
inside the body to view and detect cancers. The discovery of x-rays contributed
not only to the diagnosis but also to the treatment of cancers.
4 Cancer

Advances in anesthesiaallowed more extensive and delicate surgery. Surgeons

hoped that some cancers might be cured by surgery. John Hunter, the famous
Scottish surgeon, suggested that if a tumor had not invaded nearby tissue and
was ‘‘moveable,’’ then ‘‘There is no impropriety in removing it’’ (Dobson,
1959). In 1846, Dr. John C. Warren, a surgeon in Boston, performed what is
thought to be the first major cancer operation under general anesthesia, the
removal of a patient’s parotid tumor (Toledo, 2006). Surgery became safer as
principles of infection prevention and sterility were understood. In 1865 Joseph
Lister, an English surgeon, began using carbolic acid to sterilize surgical instru-
ments and clean surgical wounds to kill bacteria (Newsom, 2003). Once per-
formed in patients’ homes on the kitchen table, surgery moved into the
hospital setting. Surgery was also helped tremendously by the ability to transfuse
blood safely. Dr. James Blundell, a physician in London in the early 1800s, began
to study transfusion and was the first to realize that blood must be transfused
within the same species (Dzik, 2007; Blundell, 1818). The field of transfusion
was further advanced by the work of Dr. Karl Landsteiner, an Austrian physician
who discovered blood groups in the early 1900s, classifying blood into A, B, AB,
and O groups (Landsteiner, 1931). He showed that giving individuals blood from
the same group was tolerated, but that transfusion of blood from a person belong-
ing to another blood type would result in catastrophe. He was awarded the
Nobel Prize in Physiology and Medicine for this work in 1930. In the 1940s,
Dr. Charles Drew, a pioneering African American physician, was responsible
for developing improved techniques for storing blood and the development of
blood banks, which brought blood transfusions into the modern era (Scudder,
et al., 1941; Organ and Kosiba, 1987).

Seeds and Soil

As surgical advances allowed more effective resection of tumors, there
was growing recognition that removing the cancer was only part of the
treatment that was needed to control cancer. Dr. Stephen Paget observed the
tendency of breast cancers to metastasize (spread) to the liver and began to study
the mechanisms of cancer metastasis (Paget, 1889). Paget compared the cancer
cells to seeds and the sites of metastasis as the soil where a new cancer could take
root and grow. Ultimately, Paget’s work led to the understanding that systemic
treatments were as important as local control in the treatment of cancer.
At the same time, scientists began to study the causes of cancer and to under-
stand the genetic changes in cancer cells, leading to the modern era of sophisti-
cated cancer research. Most notably, in 1890, David von Hansemann, a German
pathologist, observed abnormal cell division in cancer samples and speculated