Mammography and Beyond:
Developing Technologies for
the Early Detection of
Breast Cancer
Committee on Technologies for the Early Detection of Breast Cancer
Sharyl J. Nass, I. Craig Henderson, and Joyce C. Lashof, Editors
National Cancer Policy Board
INSTITUTE OF MEDICINE
and
Division of Earth and Life Studies
NATIONAL RESEARCH COUNCIL
NATIONAL ACADEMY PRESS
Washington, DC
NATONAL ACADEMY PRESS • 2101 Constitution Avenue, N.W. • Washington, DC 20418
NOTICE: The project that is the subject of this report was approved by the Insti-
tute of Medicine and the Governing Board of the National Research Council,
whose members are drawn from the councils of the National Academy of Sci-
ences, the National Academy of Engineering, and the Institute of Medicine. The
members of the committee responsible for the report were chosen for their special
competences and with regard for appropriate balance.
Support for this project was provided by the Breast Cancer Research Founda-
tion, the Carl J. Herzog Foundation, Mr. John K. Castle, the Jewish Healthcare
Foundation (Pittsburgh, PA), the Josiah Macy, Jr., Foundation, the Kansas Health
Foundation, and the New York Community Trust. The views presented in this
report are those of the Committee on Technologies for Early Detection of Breast
Cancer and are not necessarily those of the sponsors.
Library of Congress Cataloging-in-Publication Data
Mammography and beyond : developing technologies for the early detection of
breast cancer / Committee on the Early Detection of Breast Cancer ; Sharyl J.
Nass, I. Craig Henderson, and Joyce C. Lashof, editors ; National Cancer Policy

The National Academy of Engineering was established in 1964, under the charter
of the National Academy of Sciences, as a parallel organization of outstanding
engineers. It is autonomous in its administration and in the selection of its mem-
bers, sharing with the National Academy of Sciences the responsibility for advis-
ing the federal government. The National Academy of Engineering also sponsors
engineering programs aimed at meeting national needs, encourages education
and research, and recognizes the superior achievements of engineers. Dr. William
A. Wulf is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of
Sciences to secure the services of eminent members of appropriate professions in
the examination of policy matters pertaining to the health of the public. The
Institute acts under the responsibility given to the National Academy of Sciences
by its congressional charter to be an adviser to the federal government and, upon
its own initiative, to identify issues of medical care, research, and education. Dr.
Kenneth I. Shine is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sci-
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chairman, respectively, of the National Research Council.
National Academy of Sciences
National Academy of Engineering
Institute of Medicine
National Research Council


JEAN J. LATIMER, Ph.D., Investigator, Magee-Womens Research
Institute, Assistant Professor, Department of Obstetrics,
Gynecology, and Reproductive Sciences, University of Pittsburgh,
Pittsburgh, PA
RICHARD R. NELSON, Ph.D., George Blumenthal Professor, School of
International and Public Affairs, Columbia University, New York,
NY
KENNETH OFFIT, M.D., M.P.H., Chief, Clinical Genetics Service,
Department of Human Genetics, Memorial Sloan-Kettering Cancer
Center, New York, NY
FAINA SHTERN, M.D., Director, Office of Research Affairs,
Department of Radiology, Beth Israel-Deaconess Medical Center,
Harvard Medical School, Boston, MA
vi
MICHAEL W. VANNIER, M.D., Professor and Head, Department of
Radiology, University of Iowa College of Medicine, Iowa City, Iowa
DEREK VAN AMERONGEN, M.D., M.S., FACOG, Chief Medical
Officer, Humana/ Choice Care, Cincinnati, OH
Liaison for the National Cancer Policy Board
ROBERT DAY, M.D., M.P.H., Ph.D., Emeritus President and Director,
Fred Hutchinson Cancer Research Center, Seattle, WA
Consultants
LARRY NORTON, M.D., Chief, Solid Tumors, Memorial Sloan-
Kettering, New York, NY
BARRON LERNER, M.D., Ph.D, Assistant Professor of Medicine and
Public Health (in the Center for the Study of Society and Medicine),
Columbia University, New York, NY
Staff
SHARYL J. NASS, Ph.D., Study Director
ROBERT COOK-DEEGAN, M.D., Director, National Cancer Policy

TIM BYERS, M.D., M.P.H., Professor of Epidemiology, University of
Colorado, Denver, CO
VIVIAN WAI-MEI CHEN, Ph.D., Chief & Professor of Epidemiology,
Louisiana State University, New Orleans, LA
SUSAN J. CURRY, Ph.D., Director, Center for Health Studies, Group
Health of Puget Sound, Seattle, WA
NORMAN DANIELS, Ph.D., Professor of Philosophy, Tufts University,
Newton, MA
KATHLEEN M. FOLEY, M.D., Chief of Pain Service, Memorial Sloan-
Kettering Cancer Center, New York, NY
THOMAS KELLY, M.D., Ph.D., Chairman of Department of Molecular
Biology & Genetics, Johns Hopkins University, Baltimore, MD
MARK MCCLELLAN, Assistant Professor of Economics, Stanford
University, Stanford, CA
WILLIAM MCGUIRE, M.D., Chairman and CEO, United Health
Group, Minnetonka, MN
JOHN MENDELSOHN, M.D., President, University of Texas,
Houston, TX
MONICA MORROW, M.D., Professor of Surgery, Northwestern
University, Chicago, IL
NANCY MUELLER, Sc.D, Professor of Epidemiology, Harvard School
of Public Health, Boston, MA
PILAR N. OSSORIO, Ph.D., J.D., Assistant Professor, University of
Wisconsin Law School, Madison, WI
CECIL B. PICKETT, Ph.D., Executive Vice President, Discovery
Research, Kenilworth, NJ
JOHN SEFFRIN, Ph.D., CEO, American Cancer Society, Atlanta, GA
SANDRA M. UNDERWOOD, RN, PH.D FAAN, ACS Oncology
Nursing Professor, University of Wisconsin, Milwaukee, WI
FRANCES VISCO, President, National Breast Cancer Coalition,

Joann G. Elmore, Ph.D., Assistant Professor, Department of Medicine,
University of Washington
Samuel Hellman, M.D., A.N. Pritzker Distinguished Service Professor,
Center for Advanced Medicine, The University of Chicago
Barbara J. McNeil, M.D., Ph.D., Professor and Head, Department of
Health Care Policy, Harvard Medical School
Susan Scherr, Director, Survivorship Programs, National Coalition for
Cancer Survivorship, Silver Spring, MD
x REVIEWERS
Although the reviewers listed above have provided many construc-
tive comments and suggestions, they were not asked to endorse the con-
clusions or recommendations nor did they see the final draft of the report
before its release. The review of this report was overseen by Barbara
Hulka, M.D., M.P.H., Kenan Professor, Department of Epidemiology,
University of North Carolina at Chapel Hill, appointed by the Institute of
Medicine, and Mary Jane Osborn, Ph.D., Department of Microbiology,
University of Connecticut Health Center, appointed by the NRC’s Report
Review Committee, who were responsible for making certain that an in-
dependent examination of this report was carried out in accordance with
institutional procedures and that all review comments were carefully con-
sidered. Responsibility for the final content of this report rests entirely
with the authoring committee and the institution.
Preface
xi
Breast cancer remains a leading cause of cancer death among women
in the United States. More than 180,000 new cases of invasive breast
cancer are diagnosed each year, and more than 40,000 women die of the
disease. Recent years, however, have seen improvements in survival
attributed to better treatment and earlier diagnosis. Research efforts have
been directed toward better treatment, preventive strategies, and early

play a role in the future of early breast cancer detection.
The committee also identified a number of barriers to both the devel-
opment and the dissemination of new technologies and made recommen-
dations for actions that can be taken to overcome them. Many new tech-
nologies are on the horizon and intriguing research in basic biology is
under way, but much remains to be done. We are hopeful that this report
will contribute in some small way to the efforts to improve our ability to
detect breast cancer at an early stage. The committee was impressed with
the dedication and commitment of the researchers in both the public
and the private sectors and with the governmental personnel working to
save the lives of women, and we are hopeful that their efforts will prove
fruitful.
Joyce C. Lashof
Chair
Acknowledgments
xiii
The committee wishes to thank all of the people who contributed to
this report. First and foremost we wish to acknowledge the outstanding
work of the study director, Sharyl Nass. Sharyl was responsible for the
extensive literature search, for selecting an outstanding group of speakers
for the two workshops, as well as preparing the initial drafts and revi-
sions of the entire report. Her ability to identify the key issues as well as
the key players was instrumental in carrying out the work of the commit-
tee. She was responsive to the committee members throughout, and we
all found it a pleasure to work with her. We also thank Carmie Chan and
MaryJoy Ballantyne who provided invaluable research assistance. We
were further assisted by two interns, John Kucewicz and Kevin Collins,
who made substantial contributions to the completion of Chapters 2 and
6, respectively. We also appreciate the efforts of Bianca Taylor, who took
primary responsibility for organizing the logistics of all the committee

ABBI advanced breast biopsy instrumentation
ABR American Board on Radiology
ACRIN American College of Radiology Imaging Network
ACS American Cancer Society
AHRQ Agency for Healthcare Research and Quality
ART Advanced Research and Technology
AT ataxia telangiectasia
ATP Advanced Technology Program
BBE Biofield Breast Examination
BCBSA Blue Cross/Blue Shield Association
BC-PRG Breast Cancer Progress Review Group
BCRP Breast Cancer Research Program
BCSC Breast Cancer Surveillance Consortium
BIRADS Breast Imaging Reporting and Data System
BISTIC Biomedical Information Science and Technology
Implementation Consortium
BRCA breast cancer-associated tumor suppressor gene
BSE breast self-examination
CAD computer-aided detection or diagnosis
CBE clinical breast examination
CDC Centers for Disease Control and Prevention
cDNA complementary deoxyribonucleic acid
CEA carcinoembryonic antigen
CGAP Cancer Genome Anatomy Project
xvi ACRONYMS
CIA Central Intelligence Agency
CLIA Clinical Laboratory Improvement Amendments
CNB core-needle biopsy
CPTA Center for Practice and Technology Assessment
DOD U.S. Department of Defense

ACRONYMS xvii
mRNA messenger ribonucleic acid
MRS magnetic resonance spectroscopy
NAF nipple aspiration fluid
NCHCT National Center for Health Care Technology
NCI National Cancer Institute
NEMA National Electrical Manufacturers’ Association
NIH National Institutes of Health
NIST National Institute of Standards and Technology
NMD National Mammography Database
OBBB Office of Bioengineering, Bioimaging, and Bioinformatics
OTA Office of Technology Assessment
OWH Office on Women’s Health
PCR polymerase chain reaction
PET positron emission tomography
PMA premarketing approval
PPV positive predictive value
PSA Prostate specific antigen
PTEN tumor suppressor gene
QALY quality-adjusted life year
RCP riboflavin carrier protein
RNA ribonucleic acid
RO1 a type of grant from the National Institutes of Health
RT reverse transcription
RVU relative value unit
SACGT Secretary’s Advisory Committee on Genetic Testing
SBI Society of Breast Imaging
SBIR Small Business Innovative Research
SNP single nucleotide polymorphism
SPECT Single-photon emission computed tomography

among women in the United States and is the most common non-skin-
related malignancy among U.S. women. Each year, more than 180,000
new cases of invasive breast cancer are diagnosed and more than 40,000
women die from the disease. Until research uncovers a way to prevent
breast cancer or to cure all women regardless of when their tumors are
found, early detection will be looked upon as the best hope for reducing
the burden of this disease. The hope is that early detection of breast cancer
by screening could be as effective at saving lives as the Papanicolaou
smear (Pap smear) used for cervical cancer screening.
Early detection is widely believed to reduce breast cancer mortality
by allowing intervention at an earlier stage of cancer progression. Clinical
data show that women diagnosed with early-stage breast cancers are less
likely to die of the disease than those diagnosed with more advanced
stages of breast cancer. A thorough annual physical breast examination
and monthly breast self-examination can often detect tumors that are
smaller than those found in the absence of such examinations, but data on
the ability of physical examinations alone to reduce breast cancer mortal-
ity are limited. X-ray mammography, with or without a clinical examina-
tion, has been shown in randomized clinical trials both to detect cancer at
an earlier stage and to reduce disease-specific mortality. As a result,
screening mammography has secured a place as part of routine health
maintenance procedures for women in the United States. The mortality
2 MAMMOGRAPHY AND BEYOND
rate from breast cancer has been decreasing in the United States by about
2 percent per year over the last decade, suggesting that early detection
and improved therapy are both having an impact on the disease.
Mammography is not perfect, however. Routine screening in clinical
trials resulted in a 25 to 30 percent decrease in breast cancer mortality
among women between the ages of 50 and 70. A lesser benefit was seen
among women ages 40 to 49. The benefit of screening mammography for

the biology of which is not well understood. Currently, the methods for
classification of such lesions detected by mammography are based on the
appearance of the tissue structure, and the ability to determine the lethal
potential of breast abnormalities from this classification is crude at best.
The immense burden of breast cancer, combined with the inherent
limitations of mammography and other detection modalities, have been
the driving forces behind the enormous efforts that have been and that