• Carlos L. Arteaga, MD

  • Chairperson

  • Director, Breast Cancer Program and Center for Cancer Targeted Therapies

  • Vanderbilt-Ingram Cancer Center

  • Nashville, Tennessee

  • Peter C. Adamson, MD

  • Chief

  • Division of Clinical Pharmacology & Therapeutics

  • Children's Hospital of Philadelphia

  • Philadelphia, Pennsylvania

  • Jeffrey A. Engelman, MD

  • Director of Thoracic Oncology

  • Massachusetts General Hospital

  • Charlestown, Massachusetts

  • Margaret Foti, PhD, MD (hc)

  • Chief Executive Officer

  • American Association for Cancer Research

  • Philadelphia, Pennsylvania

  • Richard B. Gaynor, MD

  • Senior Vice President

  • Global Development and Medical Affairs

  • Eli Lilly and Company

  • Indianapolis, Indiana

  • Susan G. Hilsenbeck, PhD

  • Professor, Breast Center

  • Baylor College of Medicine Cancer Center

  • Houston, Texas

  • Paul J. Limburg, MD

  • Professor of Medicine

  • Mayo Clinic College of Medicine

  • Rochester, Minnesota

  • Scott W. Lowe, PhD

  • Member

  • Cancer Biology & Genetics Program

  • Memorial Sloan-Kettering Cancer Center

  • New York, New York

  • Elaine R. Mardis, PhD

  • Co-Director, The Genome Institute

  • Washington University School of Medicine

  • St. Louis, Missouri

  • Scott Ramsey, MD, PhD

  • Fred Hutchinson Cancer Research Center

  • Seattle, Washington

  • Timothy R. Rebbeck, PhD

  • Professor

  • Dept. of Biostatistics & Epidemiology

  • University of Pennsylvania School of Medicine

  • Philadelphia, Pennsylvania

  • Andrea L. Richardson, MD, PhD

  • Assistant Professor

  • Department of Pathology

  • Brigham & Women's Hospital

  • Boston, Massachusetts

  • Eric H. Rubin, MD

  • Vice President, Oncology Clinical Research

  • Merck Research Laboratories

  • North Wales, Pennsylvania

  • George J. Weiner, MD

  • Director

  • University of Iowa Holden Comprehensive Cancer Center

  • Iowa City, Iowa

  • Shawn M. Sweeney, PhD

  • Project Leader

  • Associate Director, Translational Research

  • Philadelphia, Pennsylvania

  • Karen Honey, PhD

  • Lead Science Writer

  • Senior Managing Editor, Science Communications

  • Philadelphia, Pennsylvania

  • Jenna Bachen

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  • Philadelphia, Pennsylvania

  • Paul Driscoll

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  • Rasika Kalamegham, PhD

  • Director, Regulatory Science and Policy

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  • Nicolle Rager Fuller

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  • Bellingham, Washington

Americans are more likely to survive a cancer diagnosis today than at any other time in history. In fact, thanks to the incredible strides that have been made in biomedical research, the percentage of the U.S. population living with, through, or beyond cancer has more than tripled since the U.S. Congress passed the National Cancer Act in 1971. The AACR Cancer Progress Report 2014 chronicles the progress that has been made against the more than 200 diseases we call cancer and details how federal investment in the National Institutes of Health (NIH) and the National Cancer Institute (NCI) is transforming cancer care and the lives of patients in the United States and around the world.

Between Aug. 1, 2013, and July 31, 2014, the U.S. Food and Drug Administration (FDA) approved six new anticancer therapeutics and new uses for five previously approved anticancer therapeutics, two new cancer imaging agents, and one screening test. These advances add to the growing number of tools that health care providers have to detect, diagnose, treat, and cure some types of cancer. They are also helping patients like James (Rocky) Lagno (see p. 62), one of the individuals whose inspiring personal stories are included in the AACR Cancer Progress Report 2014, to live longer, fuller lives.

Rocky was diagnosed with lung cancer in 2011. When standard treatment with chemotherapy and radiation failed to stop the growth of his cancer, Rocky was advised by his physician to get his affairs in order; patients in his situation typically had about 13 months left to live. Rocky's tumor, however, tested positive for the ALK mutation that fuels 5 percent of non–small cell lung cancers (NSCLC). Armed with this information, Rocky's physicians prescribed him new treatments specifically designed for individuals with ALK-positive lung cancer, including ceritinib (Zykadia), a drug subsequently approved by the FDA in April 2014. Within weeks of receiving ceritinib, Rocky's condition improved dramatically, and he is currently experiencing a quality of life similar to what he had prior to his diagnosis.

Fortunately, Rocky's story is becoming more common. Paradigm-changing advances in biomedical research have made it possible to develop an increasing number of treatments precisely targeted to the unique molecular and genetic characteristics of an individual's cancer. In fact, five of the six anticancer therapeutics approved by the FDA between Aug. 1, 2013, and July 31, 2014, are compounds that actually target unique molecular and genetic characteristics.

Advances in cancer research have led to an expansion in the clinical use of genomic information, which was once reserved solely for research. Improvements in the ability to sequence and analyze large amounts of DNA have made it increasingly possible to identify the most appropriate therapy for a patient and to optimize the design and conduct of clinical trials. Collectively, these advances will spur the development of new and improved anticancer therapeutics.

The American Association for Cancer Research (AACR) is deeply grateful to all of the courageous individuals who have shared their personal experiences with the devastating collection of diseases we call cancer in the AACR Cancer Progress Report 2014. These stories, together with the advances described in this report, inspire hope for a future free of death from cancer. However, our ability to realize this future is in jeopardy because of reductions in federal investments in the NIH and NCI.

Budgets for the NIH and the NCI have failed to keep pace with inflation over the past decade. On top of these inflationary losses, direct budget cuts in 2011 and 2013 slashed NIH funding. With diminished resources, these critical agencies are not able to fund all of the promising research proposals they receive, and some researchers have had to downsize their laboratories or leave the field altogether. This reduction in our nation's research capacity and workforce has grave consequences for future innovation in biomedical research and, most importantly, for the more than 1.6 million people who are projected to receive a cancer diagnosis in the United States in 2014.

The AACR calls upon Congress and the administration to put the NIH and NCI budgets back on a path of predictable growth by providing annual budget increases at least comparable to the biomedical inflation rate. In addition, policymakers must protect the NIH from future funding cuts by taking a balanced approach to long-term deficit reduction that prioritizes the federal investment in biomedical research. We urge all AACR members and, indeed, all Americans to join us in our quest to make cancer research a national priority. Cancer survivors like Rocky Lagno and the other individuals who shared their stories in this report, as well as those who are projected to receive a cancer diagnosis in the future, are depending on it.

  • Carlos L. Arteaga, MD

  • AACR President (2014–2015)

  • Margaret Foti, PhD, MD (hc)

  • Chief Executive Officer

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Cancer Research Catalyst http://blog.aacr.org

ABOUT THE AMERICAN ASSOCIATION FOR CANCER RESEARCH

Founded in 1907, the American Association for Cancer Research (AACR) is the world's oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 35,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in 97 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with over 18,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Research has and will continue to fuel progress against cancer. This progress has been made possible by federal investment in biomedical research, which has expanded our knowledge of the biology of the more than 200 diseases we call cancer and allowed us to translate this knowledge into new and better ways to prevent, detect, diagnose, treat, and increasingly cure some of these diseases. Recent discoveries in the fields of cancer genomics and immunology have been particularly fruitful in this regard and hold great promise for the future.

An increased understanding of the role of genetic alterations in developing cancer is also the foundation on which changes are beginning to be made in the way that clinical trials are conducted and regulated. These changes can eliminate the need for large, long, multiphase trials, and it is hoped they will result in anticancer therapeutics receiving approval by the U.S. Food and Drug Administration (FDA) more rapidly than ever before.

Much of the research that has been particularly instrumental in building our current scientific foundation was funded by the federal government through the National Institutes of Health (NIH) and the National Cancer Institute (NCI).

As the oldest and largest cancer organization in the world that fosters every aspect of high-quality, innovative cancer research, the American Association for Cancer Research (AACR) is committed to increasing public understanding of cancer and the importance of lifesaving cancer research, as well as advocating for increased federal research funding for the benefit of cancer survivors and their loved ones everywhere.

The fourth AACR Cancer Progress Report to Congress and the American public serves as a comprehensive educational tool that chronicles how research is transforming lives, such as the lives of the 12 courageous individuals who have shared their experiences with cancer within the report. The report also illustrates how unwavering bipartisan support from Congress and the administration, in the form of increased funding for the NIH and NCI, is required if we are to continue to transform lives through research in the future.

Cancer in 2014

Cancer research saves lives because it is the foundation of new and better strategies for cancer prevention, detection, diagnosis, and treatment. As a result, the number of people who are living longer, higher-quality lives after a cancer diagnosis continues to rise. In fact, it is estimated that in the United States alone, nearly 14.5 million cancer survivors are alive today; an estimated 379,112 of those individuals received their cancer diagnoses as children or adolescents.

Although extraordinary advances have been and continue to be made against cancer, it is estimated that 585,720 U.S. residents, including 1,960 children and adolescents, will die from some form of cancer in 2014. Moreover, because most cancer diagnoses occur in those age 65 and older, a segment of the U.S. population that is expected to double by 2060, we face a future in which the number of cancer-related deaths will increase dramatically unless new and better ways to prevent, detect, and treat cancer can be developed. These trends are being mirrored globally, and the number of people dying of cancer worldwide is expected to increase from 8.2 million in 2012 to 14.6 million in 2035.

As the number of cancer diagnoses increases, so, too, will the economic toll of the disease. Cancer is already among the most costly diseases to the United States. The most recent NIH estimates indicated that the overall economic costs of cancer to the United States in 2009 were $216.6 billion. When these costs are compared with the NIH and NCI budgets for fiscal year 2014, which are just $30 billion and $4.9 billion, respectively, it underscores the inadequacy in federal funding for cancer research that exists today.

Developing Cancer

Cancer arises when the orderly processes that control the multiplication and life span of normal cells go awry. The resultant changes in cell behavior are predominantly a result of alterations, or mutations, in the genetic material of the cells. The specific mutation, and the order and speed at which mutations accumulate, coupled with a person's genetic makeup and lifestyle factors such as tobacco use, diet, and physical activity, influence the rate at which cancer develops and progresses.

Although genetic mutations that lead to malfunctions in a cell underpin cancer initiation and development in most cases, interactions between cancer cells and their environment—known as the tumor microenvironment—as well as interactions with systemic factors, influence the development and progression of the disease. Thus, if we are to advance our mission to prevent and cure all cancers, we must develop a more comprehensive, whole-patient understanding of cancer.

The dedicated work of researchers throughout the biomedical research enterprise has expanded and continues to expand our knowledge of cancer. As our knowledge has grown so has our ability to exploit it to improve health care. Most of the new approaches to cancer treatment more precisely attack cancers than do traditional therapies, providing patients with not just longer but also higher-quality lives.

Healthy Living Can Prevent Cancer From Developing, Progressing, or Recurring

Many of the greatest reductions in the morbidity and mortality of cancer are a result of advances in cancer prevention that have come about as we have learned more about the factors that increase a person's risk of developing cancer.

Many factors that increase the risk of developing cancer are related to lifestyle, and it is estimated that more than 50 percent of the 585,720 cancer deaths expected to occur in the United States in 2014 will be related to preventable causes. Most notable among these causes are tobacco use, obesity, lack of physical activity, exposure to ultraviolet light from the sun or tanning devices, and failure to use or comply with interventions that treat or prevent infection with cancer-associated pathogens. As a result, adopting a healthy approach to living that eliminates or reduces these risks, where possible, could significantly decrease the number of people diagnosed with certain types of cancer.

Knowing what's right doesn't mean much unless you do what's right.

THEODORE ROOSEVELT

Importantly, healthy approaches to living can also reduce cancer recurrence and improve outcomes following a cancer diagnosis. However, a great deal more research and resources are needed to understand how best to help individuals change their lifestyle.

Cancer screening is another important part of a healthy lifestyle because finding a cancer early, before it has spread to other parts of the body, increases the likelihood that treatment can be curative. Given that each individual has unique risks for developing each type of cancer, everyone should consult with his or her physicians to develop a personalized cancer-screening plan that takes into account evidence-based recommendations; the individual's own cancer risks, including family history; and the individual's tolerance of potential benefits and screening harms.

Transforming Lives Through Research

The dedicated efforts of individuals working throughout the cycle of biomedical research have led to extraordinary advances across the continuum of clinical care that are transforming lives in the United States and worldwide.

As a result of research advances, the FDA approved six new anticancer therapeutics in the 12 months leading up to July 31, 2014. During this time, the FDA also approved new uses for five previously approved anticancer therapeutics, a new use for a previously approved test for detecting the cancer-causing pathogen human papillomavirus (HPV), and new uses for two imaging agents.

Five of the new anticancer therapeutics approved by the FDA target specific molecules involved in the cancer process and are referred to as molecularly targeted therapeutics. They are part of a revolution in cancer treatment that began just over a decade ago. This revolution is changing the standard of cancer care from a one-size-fits-all approach to one in which the molecular makeup of the patient and his or her tumor dictates the best therapeutic strategy. This approach is often called personalized cancer medicine.

One of the new anticancer therapeutics approved by the FDA is also an immunotherapeutic. Cancer immunotherapy is a relatively new approach to cancer treatment that has begun to transform the lives of patients with certain cancers. There are several types of cancer immunotherapy, each of which works in a different way to train a patient's immune system to destroy the cancer. A number of cancer immunotherapeutics are showing immense promise in clinical trials, with some patients having remarkable and long-lasting responses.

As a result of research advances, more people than ever before are surviving longer and leading fuller lives after a cancer diagnosis. Despite this, cancer survivors often face serious and persistent adverse outcomes, including physical, emotional, psychosocial, and financial challenges as a result of their cancer diagnosis and treatment. The issues facing each survivor vary depending on many factors, including gender, age at diagnosis, type of cancer diagnosed, general health at diagnosis, and type of treatment received. Individuals who receive their cancer diagnoses as children, adolescents, young adults, or when elderly, are particularly vulnerable to treatment-related health issues. Research is being performed to help all cancer survivors meet the numerous challenges they face.

What Progress Does the Future Hold?

The genetic information about cancer initiation and development that we have learned through genomics research has been central to the personalized cancer medicine revolution. This new knowledge is now beginning to be used to reform how clinical trials are designed and conducted. As we look to the future, we can expect to see greater deployment of genomics and computational biology, which will spur the development of many more anticancer therapeutics and new uses for our current treatment arsenal.

Great strides have been made toward improved cancer prevention, detection, diagnosis, treatment, and, in certain cases, cure. However, some groups of individuals—in particular, racial and ethnic minorities—experience notably higher incidence of some types of cancer than the general population and/or suffer significantly poorer treatment outcomes. As research increases our understanding of the many complex and interrelated causes of cancer health disparities, we will be able to develop and implement new interventions that will transform lives, regardless of race, ethnicity, age, gender, socioeconomic status, and place of residence.

I am supremely confident that we will continue to make rapid progress in the future.

AACR PRESIDENT, 2014–2105, CARLOS L. ARTEAGA, MD

A Prescription for Increasing the Rate of Progress Against Cancer

Federal support for the NIH and NCI has facilitated extraordinary progress against cancer. It has also catalyzed an explosion in our knowledge of the biology of cancer and understanding of how to apply this knowledge to provide new ways to reduce the burden of this disease. Despite these opportunities, many challenges must be overcome if we are to realize our goal of defeating cancer.

First and foremost, we must continue to pursue a comprehensive understanding of the biology of cancer at all stages and to develop new approaches to translating this knowledge into health care advances that will save lives. To do this, we must make investing in biomedical research a national priority. Only by investing in research talent, tools, and infrastructure and by advancing policies that drive innovation and the translation of new knowledge for the benefit of patients will we be able to capitalize on past federal investments in biomedical research and seize opportunities to forge ahead to the day when cancer is removed as a major health threat to all.

AACR CALL TO ACTION

We are now at a crossroads in our country's long struggle to prevent and cure cancer; we must choose between two paths, but there is only one viable path forward to continue transforming lives.

On the viable path we seize the momentum at this exciting time in biomedical research by committing to budget increases for the NIH and NCI so that the remarkable progress of the past can continue at a rapid pace.

To take the alternative path is simply unacceptable. This particularly dangerous path leads us to a place where federal funding for biomedical research remains stagnant or, even worse, declines, seriously jeopardizing the rate at which we are able to make progress. On this path, breakthroughs and discoveries will be slowed, meaning that delivery of the cures that patients and their loved ones desperately need is delayed. Early-career researchers may be forced to leave science for other fields, further jeopardizing continued future progress.

The AACR respectfully urges Congress to do the right thing for cancer patients and our nation and choose the only viable path forward, which is to:

Prioritize the growth of the NIH and NCI budgets at a predictable, robust pace by providing annual budget increases at least comparable to the biomedical inflation rate.

Rededicating our country to the promise of biomedical research requires strong leadership from the administration and Congress. It also requires a commitment from all Americans to support federal funding for biomedical research and to communicate this view to policymakers.

As a country we must set priorities and make difficult choices at this fiscally challenging time in our history. Our federal government can do no better than invest robustly in the NIH and the NCI so that the path forward will lead us to a brighter future for the millions of people whose lives have been touched by cancer.

IN THIS SECTION YOU WILL LEARN:

  • THERE ARE NEARLY 14.5 MILLION CANCER SURVIVORS IN THE UNITED STATES.

  • IN THE UNITED STATES, MORE THAN 1.6 MILLION PEOPLE ARE PROJECTED TO RECEIVE A CANCER DIAGNOSIS IN 2014, AND MORE THAN 585,000 ARE EXPECTED TO DIE FROM THE DISEASE.

  • THE NUMBER OF NEW CANCER CASES PER YEAR IS PREDICTED TO RISE TO ALMOST 2.4 MILLION IN THE UNITED STATES, AND MORE THAN 24 MILLION GLOBALLY IN 2035.

  • CANCER IS A COSTLY DISEASE, BOTH IN THE UNITED STATES AND WORLDWIDE.

Research Fuels Progress Against Cancer

Research continues to be our best defense against cancer. It improves survival and quality of life for millions of individuals by spurring the development of new and better ways to prevent, detect, diagnose, treat, and, increasingly, cure some of the more than 200 diseases we call cancer.

This progress against cancer is the result of the dedicated efforts of many individuals working together as part of the broader biomedical research community (see sidebar on The Biomedical Research Community, p. 2). It takes many years of work by all stakeholders within this community to bring a new medical product from initial research discovery to approval by the U.S. Food and Drug Administration (FDA). This achievement was attained for six new anticancer therapeutics between Aug. 1, 2013, and July 31, 2014 (see Table 1, p. 3). During this period, the FDA also approved new uses for five previously approved anticancer therapeutics, two imaging agents, and one screening test, thereby increasing the number of patients benefiting from them.

As a result of advances like these, the number of people in the United States who survive their cancer continues to increase year after year (see Figure 1). In fact, since 1971, the year the U.S. Congress passed the National Cancer Act, the percentage of the U.S. population living with, through, or beyond a cancer diagnosis has more than tripled (1–4).

The basic, translational, and clinical research that has fueled and continues to fuel extraordinary progress against cancer is made possible by investments from the federal government, philanthropic individuals and organizations, and the private sector. Of particular importance are the investments in biomedical research supported by the federal government and administered through the National Institutes of Health (NIH) and the National Cancer Institute (NCI). Without sustained support of biomedical research from all sectors, continued progress against cancer is in jeopardy.

TABLE 1

NEWLY FDA-APPROVED THERAPEUTICS, AND INDICATIONS FOR THE TREATMENT AND IMAGING OF CANCER: AUGUST 1, 2013-JULY 31, 2014

NEWLY FDA-APPROVED THERAPEUTICS, AND INDICATIONS FOR THE TREATMENT AND IMAGING OF CANCER: AUGUST 1, 2013-JULY 31, 2014
NEWLY FDA-APPROVED THERAPEUTICS, AND INDICATIONS FOR THE TREATMENT AND IMAGING OF CANCER: AUGUST 1, 2013-JULY 31, 2014

Cancer: An Ongoing Challenge

Even though definitive, measurable progress has been and continues to be made against cancer, this devastating collection of diseases continues to pose an enormous challenge for researchers, clinicians, and patients. In fact, cancer remains the leading cause of disease-related death among children in the United States (1).

TABLE 2

ESTIMATED INCIDENCE AND MORTALITY FOR SELECT CANCERS

ESTIMATED INCIDENCE AND MORTALITY FOR SELECT CANCERS
ESTIMATED INCIDENCE AND MORTALITY FOR SELECT CANCERS

Among the challenges we face is the fact that advances have not been uniform for all types of adult and pediatric cancer (see Table 2, p. 4 and Table 3, p. 6). Thus, whereas overall five-year survival rates for women with invasive breast cancer and men with prostate cancer are 89 percent and 99 percent, respectively, those for adult patients with pancreatic, liver, or lung cancer are very low, at 6 percent, 16 percent, and 17 percent, respectively (1). Similarly, whereas the overall five-year survival rate for childhood acute lymphoblastic leukemia (ALL) is 90 percent, it is only 64 percent for children diagnosed with rhabdomyosarcoma (1).

Moreover, advances have not been uniform for all patients diagnosed with a given cancer type. Five-year survival rates vary with stage at diagnosis and among different segments of the population (see sidebar on Cancer Health Disparities in the United States).

TABLE 3

COMPARISON OF FIVE-YEAR SURVIVAL RATES FOR PEDIATRIC CANCERS (0-19 YRS) BETWEEN 1975-79 AND 2003-09

COMPARISON OF FIVE-YEAR SURVIVAL RATES FOR PEDIATRIC CANCERS (0-19 YRS) BETWEEN 1975-79 AND 2003-09
COMPARISON OF FIVE-YEAR SURVIVAL RATES FOR PEDIATRIC CANCERS (0-19 YRS) BETWEEN 1975-79 AND 2003-09

Although tremendous progress against cancer has been made (see Table 2, p. 4 and Table 3, p. 6), the number of Americans receiving a cancer diagnosis each year has been increasing steadily for the past four decades, and this number is expected to rise significantly, reaching almost 2.4 million in 2035 (6). This projected increase is largely because cancer is, primarily, a disease of aging. Most cancer diagnoses occur in those age 65 and older (7), and this portion of the U.S. population is expected to double by 2060 (8). High rates of obesity and continued use of tobacco products by 18 percent of adults in the United States (9), both of which are linked to an elevated risk for numerous types of cancer (10, 11), are contributing to the problem.

This rise in cancer cases is directly leading to an increase in the number of Americans dying of cancer. In fact, it is estimated that 585,720 people will die of some form of cancer in 2014 (1). Unless more effective strategies for cancer prevention, early detection, and treatment can be developed, it will not be long before cancer overtakes heart disease as the leading cause of death for all Americans, as it already is among the U.S. Hispanic population (12, 13) (see Figure 2, p. 7).

These challenges are not unique to the United States; they are also global problems. In 2012 alone, it is estimated that almost 14.1 million people worldwide received a diagnosis of cancer and 8.2 million died of the disease (6). Without significant new advances in cancer prevention, detection, and treatment, these numbers are projected to rise to 24 million new cancer cases and 14.6 million cancer deaths in 2035.

Cancer: A Costly Disease. Research: A Vital Investment

The immense burden of cancer is clear not just from the large number of lives it touches but also from its significant economic impact. Cancer is among the costliest of diseases to the United States. The most recent NIH estimates indicate that the overall economic costs of cancer in 2009 were $216.6 billion: $86.6 billion in direct medical costs (i.e., the costs for all health expenditures) and $130.0 billion for indirect costs (i.e., costs for lost productivity due to premature death) (1). These costs stand in stark contrast to the NIH and NCI budgets for fiscal year 2014, which are just $30 billion and $4.9 billion, respectively.

The global economic toll of cancer is also enormous. It has been estimated that the 12.9 million new cases of cancer diagnosed in 2009 cost the world $286 billion that year alone (14). As the number of cancer cases rises, so, too, does cost. The 13.3 million new cases of cancer diagnosed worldwide in 2010 are estimated to have cost $290 billion, and the 21.5 million new cancer cases anticipated to occur in 2030 are projected to cost $458 billion (15).

The rising economic and personal burden of cancer underscores the urgent need for more research to develop new prevention and treatment approaches. Recent advances, some of which are highlighted in this report, were made as a direct result of the cumulative efforts of researchers across the spectrum of research disciplines. Much of their work, and the advances that followed, was a direct result of research funding from the federal government. Thus, it is imperative that Congress and the administration increase investments in the primary federal agencies that support this vital research, the NIH and NCI.

IN THIS SECTION YOU WILL LEARN:

  • CHANGES IN THE GENETIC MATERIAL IN A NORMAL CELL UNDERPIN CANCER INITIATION AND DEVELOPMENT IN MOST CASES.

  • A CANCER CELL's SURROUNDINGS INFLUENCE THE DEVELOPMENT AND PROGRESSION OF DISEASE.

  • THE MOST ADVANCED STAGE OF CANCER, METASTATIC DISEASE, ACCOUNTS FOR MORE THAN 90 PERCENT OF CANCER DEATHS.

  • THE MORE WE KNOW ABOUT THE BIOLOGY OF CANCER, THE MORE PRECISELY WE CAN PREVENT, DETECT, DIAGNOSE, AND TREAT IT.

Cancer arises when the orderly processes that control the multiplication and life span of normal cells go awry. As a result, the cells start multiplying uncontrollably, fail to die when they should, and accumulate, either forming a tumor mass in any organ or tissue of the body or crowding out the normal cells in the blood or bone marrow. Over time, tumors can enlarge as more cells accumulate, until some cells gain the ability to invade local tissues and spread, or metastasize, to distant sites (see Figure 3). The emergence of metastatic cancer is a dire occurrence that accounts for more than 90 percent of cancer deaths.

The changes in cell behavior that occur during the initiation, development, and progression of a cancer are predominantly a result of changes in the genetic material of the cells. The length of time it takes for a cancer to develop varies widely and depends on the identity, order, and speed at which changes in the genetic material accumulate. Numerous interrelated factors, such as a person's genetic makeup and environmental factors like tobacco use, diet, associated illnesses, and other exposures, also influence this rate.

Cancer Development: Influences Inside the Cell

The entirety of a person's deoxyribonucleic acid (DNA) is called their genome (see sidebar on Genetic and Epigenetic Control of Cell Function). A “mutation” is a change in the type or order of the bases that make up the DNA code. Because a cell reads the DNA code to produce the proteins it needs to function, mutations in the code can result in altered protein amounts or functions (see sidebar on Genetic Mutations, p. 11). If these changes alter proteins that control certain critical cell functions, such as cell multiplication or survival, they can ultimately lead to cancer.

Many different types of mutations can lead to cancer. Over the years, researchers have determined that cancer-associated mutations are most often found in one of two classes of genes: (proto)oncogenes and tumor suppressor genes.

Mutations in (proto)oncogenes lead to altered proteins that can drive the initiation and progression of cancer. Tumor suppressor genes code for proteins that normally repair damaged DNA or repress signals that promote cell survival and multiplication. Alterations in these genes can lead to cancer by permitting the accumulation of harmful DNA mutations or by allowing overactive cells to survive or begin growing again.

In addition to mutations in their DNA, most cancer cells also have profound abnormalities in their epigenomes when compared with normal cells of the same tissue. In many cases, these epigenetic defects work in conjunction with permanent changes in the DNA of the cell to promote cancerous behaviors. One of the most exciting recent discoveries is that some epigenetic abnormalities may be reversible.

Cancer Development: Influences Outside the Cell

It is clear that cancer develops as a result of alterations to the genetic material of a cell that lead to malfunctions in its behavior. Research has revealed, however, that interactions between cancer cells and their environment—known as the tumor microenvironment—as well as interactions with systemic factors, are an important part of cancer development (see sidebar on Cancer Growth: Local and Global Influences, p. 12). This means that cancer is much more complex than an isolated mass of proliferating cancer cells. Therefore, if we are to advance our mission to prevent and cure all cancers, we must develop a more comprehensive, whole-patient understanding of cancer.

Some components of the tumor microenvironment are normal parts of the tissue in which the cancer is growing. Others are systemic factors that transiently affect the tumor microenvironment as they percolate through it. Yet others are actively recruited or formed as a result of signals emanating from the cancer cells themselves. Whether passive participants or active recruits, the various components of the microenvironment are often exploited by cancer cells to advance their growth and survival.

Cancer Development: Exploiting Our Expanding Knowledge to Improve Health Care

Fundamental research expands our knowledge of the biology of cancer (see sidebar on Fundamental Research: The Foundation of Today's Treatments and Tomorrow's Advances, p. 13). As our knowledge has grown, so has our ability to exploit it to develop new and improved approaches to cancer prevention, detection, diagnosis, and treatment. The majority of the new approaches more precisely attack cancers than do traditional therapeutics, providing patients with not just longer but also higher-quality lives.

It is clear that, through this fundamental research, which is largely supported by the NIH and NCI, we have developed a greater understanding of the processes by which cancer starts, progresses, and results in disease. This knowledge has yielded significant progress in preventing, detecting, diagnosing, and treating cancer. Continued progress, therefore, will be made only through additional research, and as such, it is imperative that the administration and Congress support the primary federal agencies that support this vital research, the NIH and NCI.

IN THIS SECTION YOU WILL LEARN:

  • MORE THAN HALF OF CANCER DEATHS IN THE UNITED STATES ARE A RESULT OF PREVENTABLE CAUSES.

  • TOBACCO USE IS RESPONSIBLE FOR ALMOST 30 PERCENT OF CANCER DEATHS IN THE UNITED STATES.

  • ULTRAVIOLET RADIATION FROM THE SUN AND INDOOR TANNING DEVICES CAUSES THE MAJORITY OF SKIN CANCERS.

  • DEVELOPING A PERSONALIZED CANCER-SCREENING PLAN WITH YOUR PHYSICIANS IS PART OF A HEALTHY APPROACH TO LIVING.

  • ABOUT ONE IN EVERY FIVE CANCER DIAGNOSES WORLDWIDE IS ATTRIBUTABLE TO PERSISTENT INFECTION WITH A PATHOGEN. INFECTION WITH MANY KNOWN CANCER-CAUSING PATHOGENS CAN BE PREVENTED BY VACCINATION OR TREATMENT WITH MEDICINES.

  • UP TO ONE-THIRD OF ALL NEW CANCER DIAGNOSES IN THE UNITED STATES ARE RELATED TO BEING OVERWEIGHT OR OBESE, PHYSICAL INACTIVITY, AND/OR POOR DIETARY HABITS.

Many of the greatest reductions in cancer morbidity and mortality are a result of advances in cancer prevention and early detection. These advances were enabled by translating the discoveries of the causes and progressive nature of cancer into effective new clinical practices and public education and policy initiatives.

Central to preventing cancer is the identification of factors that increase a person's risk of developing cancer and eliminating or reducing these factors where possible (see Figure 4, p. 15). As research has enhanced our knowledge of cancer risk factors, we have learned that more than 50 percent of the 585,720 cancer deaths expected to occur in the United States in 2014 will be related to preventable causes (16).

Many factors that increase the risk of developing cancer are related to lifestyle; thus, adopting a healthy approach to living, where possible, can eliminate or reduce the risk of some cancers (see Figure 5, p. 15). Moreover, many healthy approaches to living can also reduce cancer recurrence and improve outcomes following a cancer diagnosis. However, a great deal more research and many more resources are needed to understand how best to help individuals change their lifestyle.

Adopting Healthy Approaches to Living

Tobacco use is responsible for almost 30 percent of cancer deaths each year in the United States (1) (see Figure 6, p. 16). As a result, one of the most effective ways a person can lower the risk of developing cancer is to eliminate tobacco use (see sidebar on Reasons to Eliminate Tobacco Use, p. 17). This relationship between tobacco use and cancer was first brought to the public's attention 50 years ago, when the U.S. Surgeon General's report on “Smoking and Health” was published (17). Since then, smoking rates among U.S. adults have more than halved, and as a result, an estimated 800,000 deaths from lung cancer were avoided between 1975 and 2000 (18).

Unfortunately, the rate of decline in smoking prevalence in the United States has slowed in recent years (18). In fact, almost 70 million individuals age 12 or older are regular users of tobacco products (20).

If we are to eradicate one of the biggest threats to public health, researchers, clinicians, advocates, and policymakers must continue to work together. Several steps that could be taken to achieve this goal are outlined in this year's Surgeon General's report, “The Health Consequences of Smoking—50 Years of Progress,” (see sidebar on Eliminating Tobacco Use Faster, p. 93) (18). Of particular importance is the regulation of additional tobacco products by the FDA.

Other healthy approaches to living that can significantly reduce cancer risk are maintaining a healthy weight, which is defined as a body mass index (BMI) between 18.5 and 24.9 kg/m2 for adults over 20 years of age; keeping active; and eating a balanced diet (see sidebar on Reasons to Maintain a Healthy Weight and Keep Active, p. 18). The impact of adopting these aspects of a healthy lifestyle could be enormous because it is estimated that one-third of all new cancer diagnoses in the United States are related to being overweight or obese, not getting enough physical activity, and/or having poor dietary habits (10, 16). Moreover, more than one-third of adults, or more than 72 million individuals, and 17 percent of youth in the United States are obese (21, 22).

Fortunately, regular physical activity, independent of body fatness, can decrease the risk of developing certain cancers (23). However, nearly half of adults in the United States do not meet the recommended guidelines for aerobic physical activity (25) (see sidebar on Physical Activity Guidelines, p. 19). Moreover, sedentary behavior, independent of body mass and periodic physical activity, can increase the risk of developing certain types of cancer (24).

Realization of the enormity of personal and financial health care problems resulting from overweight and obesity, lack of physical activity, and/or poor dietary habits has led to some progress in recent years. For example, the proportion of U.S. adults who walk for transportation, fun, or exercise rose 6 percent from 2005 to 2010 (26). In addition, when considering the U.S. population as a whole, the prevalence of obesity has remained stable since 2003 (21). However, this is not true for all segments of the population.

Beyond preventing the development of some cancers, following the physical activity guidelines may also improve outcomes for individuals diagnosed with certain types of cancer, in particular breast, colorectal, and prostate cancers; reduce risk of disease recurrence and metastasis; and increase the chance of long-term survival (27–29).

Although small improvements in maintaining a healthy weight and increasing physical activity have been made, more action is urgently needed. Concerted efforts by individuals, families, communities, schools, workplaces and institutions, health care professionals, media, industry, government, and multinational bodies are required to develop effective and comprehensive strategies to promote the maintenance of a healthy weight and the participation in regular physical exercise. One new strategy, Park Rx, an initiative of the National Park Service, seeks to encourage health care providers to help patients establish an exercise routine by effectively using their neighborhood parks.

Another way that individuals can reduce their risk of developing cancer, specifically the three main types of skin cancer—basal cell carcinoma, squamous cell carcinoma, and melanoma—is by limiting their exposure to ultraviolet (UV) radiation (see sidebar on Reasons to Protect Your Skin). In fact, the International Agency for Research on Cancer (IARC), an affiliate of the World Health Organization, considers exposure to UV radiation from any source as “carcinogenic to humans” (30), alongside agents such as plutonium and cigarettes.

Despite this, half of all adults in the United States report at least one sunburn in the past 12 months and 5 percent report using a UV indoor tanning device at least once, with many using these devices 10 or more times a year (37, 38). Moreover, 13 percent of all high school students and 21 percent of high school girls report using an indoor UV tanning device in the past year (39).

Given that many cases of skin cancer are preventable, it is important that everyone work together to develop and implement more effective policy changes and public education campaigns to help reduce the health and economic burdens of the disease. For example, initiatives aimed at increasing the number of individuals who adopt sun-safe habits and tighter regulation of indoor tanning would dramatically reduce the incidence of skin cancer (see sidebar on Sun-safe Habits).

Persistent infection with a number of pathogens—bacteria, viruses, or parasites that cause disease—can result in certain types of cancer (40, 41) (see Table 4, p. 22). In fact, pathogens are estimated to cause about 2 million cancer cases each year, with more than 90 percent of these cases attributable to just four pathogens—Helicobacter pylori, hepatitis B virus (HBV), hepatitis C virus (HCV), and human papilloma virus (HPV) (42) (see Figure 7, p. 23).

This knowledge has enabled the development of strategies to eliminate or prevent infection with these cancer-associated pathogens (see sidebar on Cancer-causing Pathogens: Prevention and Elimination, p. 24). Consulting with a physician and following his or her advice regarding the use of these strategies can reduce an individual's risk of certain cancers and is part of a healthy approach to living.

TABLE 4

INFECTIOUS CAUSES OF CANCER

INFECTIOUS CAUSES OF CANCER
INFECTIOUS CAUSES OF CANCER

Despite the availability of strategies to eliminate or prevent infection with some cancer-associated pathogens, researchers estimate that pathogen-related cancers account for about 20 percent of cancer diagnoses worldwide (40) (see Figure 7, p. 23). Thus, it is clear that these strategies are not being used optimally and that a dramatic reduction in the global cancer incidence could be achieved by more effective implementation. In fact, the CDC estimates that in 2012, only 33 percent of girls ages 13–17 in the United States had received the recommended three doses of HPV vaccine (60). Moreover, this percentage varies widely among states, with fewer than 26 percent of girls completing the vaccine course in six states, and the lowest rate being just 12.1 percent (44). Further, the “President's Cancer Panel 2012–2013 Report” stated that in the United States alone, more than 50,000 cases of cervical cancer and thousands of cases of other types of cancer could be prevented if 80 percent of those for whom the HPV vaccine is recommended—girls and boys ages 11 and 12, respectively—were to be vaccinated (44) (see sidebar on The “President's Cancer Panel Report,” p. 25).

Research has provided and continues to increase our knowledge of the causes of cancer and the timing, sequence, and frequency of the genetic, molecular, and cellular changes that drive cancer initiation and development. This knowledge provides us with unique opportunities for developing ways to prevent cancer onset or to detect a cancer and intervene earlier in its progression. Finding a cancer early, as Congressman Ron Barber (see p. 26) did in 2012, before it has spread to other parts of the body, makes it more likely that a patient can be treated successfully. Cancer screening is therefore an important part of a healthy lifestyle.

I was diagnosed with oral cancer just a few days after election night in November 2012. I was extremely fortunate that my cancer was caught early, at stage 1. This meant that the only treatment I needed was surgery to remove the tumor and that my outlook is very good. My experience taught me that it is vital that you pay attention to what your body is telling you and that you don't delay getting anything unusual checked out.

It was the fall of 2012 when I noticed what seemed like a blister on my tongue that didn't heal quickly. I tried a number of topical treatments, but it just wasn't going away so my dentist sent me to an oral surgeon to have it biopsied.

I received the biopsy results at an extremely stressful time—seven days after election night, which was during the 11 days it took to complete the vote count for my district, the 2nd Congressional District of Arizona.

I immediately contacted the University of Arizona Cancer Center in Tucson, which is one of the country's premier cancer centers. Fortunately, the center had recently established an ENT [ear, nose, and throat] team specializing in the treatment of cancers like mine, so I felt I was in the best place possible.

The medical team told me that because my cancer had been caught at an early stage, I should have surgery as soon as possible and that I would need regular follow-up visits. My tumor was removed just before Thanksgiving, and I was fully recovered in time to be sworn into my first full term in Congress on Jan. 3, 2013.

For the first year after surgery, I had follow-ups with my ENT oncologist at the University of Arizona Cancer Center every four weeks, but now it is every eight weeks. My doctors say we could probably go longer between visits, but to be on the safe side they want to continue with this schedule. They also tell me that if anything changes at all I should call and be seen right away, so I keep a pretty constant watch on what's going on. Every now and again, if I bite my tongue or have a little sore, I'll go and be checked, but it has always turned out to be nothing.

One of the things that helped me to get through my experience, other than my fantastic specialty medical team, was the enormous support I got from my wife, my children, my grandkids, and my friends. Sometimes it is hard to ask for help or to accept it, but when you are dealing with a disease like cancer, you really can't hold back—you just have to welcome the support, and I got plenty of it.

By sharing my story, I hope to remind everyone, in particular my colleagues in Congress, that cancer is not an abstract national problem but something that can happen to anybody in the blink of an eye. We are all susceptible. I tend to be kind of stoic, but the truth is that inside I was thinking, is this going to be the beginning of the end? What I learned, though, was that our knowledge about cancer is growing and we have so much good research, and more to come, that I hope it is the beginning of pathways to prevention, treatment, and cure. But to achieve these goals, we need to stay on the cutting edge, and to do this we need more funding for the National Institutes of Health.

THE HONORABLE RON BARBER

(D-ARIZ.)

AGE 69

TUCSON, ARIZONA

It is vital that you pay attention to what your body is telling you and that you don't delay getting anything unusual checked out.

Over 42,000 individuals in the United States are expected to develop cancer of the oral cavity or pharynx (mouth and upper throat) in 2014.

Screening to detect cancer in individuals showing no signs or symptoms of the disease they are being screened for can have tremendous benefits (see sidebar on Cancer Screening). However, it can also cause unintended harm, and this has made it difficult to develop strategies for screening for the majority of cancer types. For a screening program to be successful, it must meet two important criteria: It must decrease deaths from the screened cancer, and the benefits it provides must outweigh any harms. Determining whether a screening program meets these criteria requires an enormous amount of research and careful analysis of the data generated.

In the United States, an independent group of experts convened by the Public Health Service rigorously evaluates clinical research to make evidence-based recommendations about clinical preventive services, including cancer-screening tests. These experts form the U.S. Preventive Services Task Force (USPSTF). As of Aug. 1, 2014, the USPSTF recommended that certain segments of the general population be screened for just four types of cancer (see sidebar on USPSTF Cancer-screening Recommendations, p. 29). In addition to considering evidence regarding potential new screening programs, the USPSTF routinely evaluates new research regarding established screening programs, and can revise recommendations if deemed necessary.

Although cancer screening is part of a healthy approach to living, it can be difficult for individuals to ascertain which cancers to be screened for and when. The USPSTF and other relevant professional societies' recommendations are evidence-based guidelines that can help, but they are only one factor to consider when making decisions about cancer screening.

People have their own unique risks for developing each type of cancer. These risks are determined by genetic, molecular, cellular, and tissue makeup, as well as by lifetime exposures to the large number of factors that can increase the risk of developing cancer (see Figure 4, p. 15). As a result, each individual should consult with his or her physicians to develop a personalized cancer-screening plan that takes into account evidence-based recommendations; the individual's own cancer risks, including family history; and the individual's tolerance of potential screening harms (see sidebar on Cancer Screening, p. 28). Importantly, the risk for different types of cancer can vary over time—for example, risk for most cancers increases with age—so it is important that individuals continually evaluate, and update if necessary, their personalized cancer-screening plans.

Some generally healthy individuals are at increased risk of certain cancers because they inherited a cancer-predisposing genetic mutation (see sidebar on How Do I Know If I Am at High Risk for Developing an Inherited Cancer?). However, inheriting a cancer-predisposing genetic mutation is a relatively rare occurrence. In fact, only about 5 percent of all new cases of cancer diagnosed in the United States each year are caused by such mutations (63). To date, not all potentially inheritable causes of cancer have been identified, but if an individual suspects that a relative has a cancer caused by one of the 17 known cancer-predisposing genetic mutations (see Table 5), he or she should consult a physician and consider genetic testing for verification.

As part of a healthy approach to living, persons who are at risk for developing an inherited cancer—both those who learn they carry a known cancer-predisposing genetic mutation and those who fulfill criteria for being at risk—should consult with their physicians to determine how this influences their personalized cancer-prevention and -screening plans. Some patients may be able to reduce their risk of developing cancer by modifying their behaviors. Others might need to increase their participation in screening or early detection programs or even consider taking a preventive medicine or having risk-reducing surgery (see Tables 6 and 7).

TABLE 5

INHERITED CANCER RISK

INHERITED CANCER RISK