This is an archive page. The links are no longer being updated.
Andrew von Eschenbach, M.D.
on Labor, Health and Human Services,
Education, and Related
Health, Education, Labor and Pensions
on Public Health
Members of the Subcommittees. I am Andrew von Eschenbach,
M.D., Director of the National Cancer Institute (NCI).
I am pleased to present my first official testimony as
the new Director of NCI before these distinguished Committees
on the very important public health topic of mammography.
I would like
to begin with a very concise summary of the position of
NCI and the Department of Health and Human Services (HHS)
on mammography and our current plans. I will expand on
these later in my testimony. Let me assure you that NCI
is collaborating with other agencies within the Department,
including the Agency for Healthcare Research and Quality
(AHRQ) and the Centers for Disease Control and Prevention
(CDC), to ensure that together we are providing the latest
science, clinical recommendations, and programs to prevent,
screen, diagnose, and treat breast cancer.
mortality continues to fall, and that is very good news.
Death rates from breast cancer first began to decline
in 1989 at 1.4 percent per year. More recently the decrease
has improved to 3.2 percent per year. This is a significant
decline for all ages. Unfortunately, the decline began
later (1993) and is lower for Black women, whose breast
cancer death rates are 33 percent higher than rates for
We feel confident
that mammography has contributed to this decline, but
mammography alone has not driven this trend. Advances
in therapy, including adjuvant therapy (both hormonal
and chemotherapy) and chemoprevention approaches (such
as tamoxifen) have also played a role. Unfortunately,
the current debate appears to be focused on this single
component in the equation. What we need to keep in mind
is that many factors taken together are responsible, all
are important, and we cannot eliminate any from our current
approach to breast cancer. Women need unimpeded access
to prevention, screening, treatment, and supportive care
to win their battle against breast cancer, and we need
to keep our focus on the sum of the equation: longer life
coupled with better quality of life.
to recommend mammography screening for women beginning
in their forties. This is consistent with the recently
released report of the U.S. Preventive Services Task Force
(USPSTF), an independent panel of private-sector experts
in prevention and primary care sponsored by AHRQ. On February
21, 2002, HHS Secretary Tommy Thompson released an updated
recommendation from the USPSTF that recommended screening
mammography every 1-2 years for women ages 40 and over.
As Secretary Thompson stated, "I believe that this recommendation
reaffirms the importance of mammography and should substantially
allay concerns about its value in safeguarding the health
that mammography detects early tumors when they are smaller,
detects more tumors, and gives a woman more options for
treatment. These benefits are substantial by themselves.
The controversial issue is whether it saves lives in the
long run. We have reviewed the evidence and the USPSTF
recommendation, and we conclude that the weight of the
evidence shows that mammography saves lives through early
detection and treatment at an earlier stage. We will continue
to monitor and consider any new information about mammography.
However, mammography as a screening technology is only
one tool, and we are pursuing a strong research agenda
to develop other methods, such as improved imaging techniques,
to design better ways to screen for breast cancer in the
future. We will continue to work closely with other Institutes
and Centers of the National Institutes of Health (NIH),
organizations, and breast cancer patient advocates to
ensure that research findings are translated quickly into
How do we know
what we know about mammography? The use of x-ray imaging
for the detection of breast cancer came into use in the
1960s, following technological advances that resulted
in better images that were easier to reproduce and interpret.
Initially used to assist in diagnosis, mammography was
also studied for its potential use as a screening tool.
Several randomized clinical trials of mammography have
been conducted since 1963, and as these studies have been
completed and the data analyzed, the findings have added
to the total body of evidence we have today. At various
times in the past decades, different organizations such
as the American College of Radiology, the American Cancer
Society, NCI, and others have reviewed the available data
on screening mammography, have drawn conclusions about
the strength of that evidence, and have made recommendations
or statements about its appropriate role and use. Specifically,
in 1993 NCI convened a workshop of experts to examine
the available literature and data on screening mammography
and to issue a statement of the strength of that evidence.
At that time, the NCI concluded that the evidence supported
mammography for women over age 50 but not under age 50.
In the intervening
years, more data were obtained on the women who participated
in the trials, and there were now enough women who had
entered the trials in their 40s to more accurately assess
the impact of mammography for women in their 40s. In 1997,
there was a National Institutes of Health
where an extensive review was reported of all of the available
information on screening mammography. Following that meeting
and subsequent deliberations by our respective boards
of advisors, both NCI and the American Cancer Society
(ACS) released modified breast cancer screening recommendations.
As of 1997, both NCI and ACS recommend mammography for
women starting at age 40, although on somewhat different
screening intervals. Both organizations also emphasized
the importance of informed decision making about mammography.
by Olsen and Gotzsche that was published in The Lancet
last fall reviewed the seven randomized clinical trials
of mammography that were done in the 1960s through 1980s.
They considered technical details of the trials, such
as how women were randomized into mammography and control
groups, and whether breast cancer as a cause of death
was determined accurately. The authors found technical
problems in five of the clinical trials, all of which
had shown a reduction in mortality associated with mammography;
they therefore called into question the value of mammography.
The NCI has reviewed
very carefully the Olsen and Gotzsche critique, and we
have concluded that their review does not warrant a departure
from our current recommendation on mammography. Over 400,000
women took part in the seven randomized clinical trials
that were reviewed by Olsen and Gotzsche. They examined
each of these trials and identified potential flaws that
could have influenced the findings in several of the studies.
They gave little weight to the reported benefits from
five of the seven trials and went on to conclude that
the totality of evidence did not support screening mammography.
However, difference of opinion among experts regarding
design of these studies does not in itself prove that
the conclusions are wrong. After careful deliberation
of the arguments, the NCI has concluded that the value
of mammography has not been refuted.
Let me give you
two examples of what Olsen and Gotzsche said and why we
disagree. The first clinical trial of mammography
was begun in New York City in the 1960s. It was
state-of-the-art at that time. Olsen and Gotzsche
pointed out that after the participants were randomized
into two groups, one group to be screened and the other
not to be screened, a larger number of women were excluded
from the group to be screened than from the unscreened
group. This suggested the possibility that women
diagnosed with breast cancer before the study began could
be included in the screened group, but not in the unscreened
group, resulting in a bias that would make it appear that
mammography was useful, when this might only have been
an artifact of study design. A scientific clinical
trials expert who worked on this trial corroborated that
during the nineteen-year follow-up period, any woman with
breast cancer diagnosed prior to the onset of the study
was excluded from both groups. This would correct
for the potential bias suggested by Olsen and Gotzsche.
A second claim
by Olsen and Gotzsche was that in several studies, the
cause of death in the mammography screened group was more
often called "died with breast cancer," while in the comparison
group, women were classified as "died of breast cancer."
They claimed that this could also be a bias in favor of
mammography. However, this is also what you would
see if mammography were in fact saving lives. Therefore,
the NCI concluded that Olsen and Gotzsche have not refuted
the evidence that mammography saves lives.
The authors also
failed to consider that since the time these trials were
conducted, there have been improvements in mammography
and the technique of biopsy as well as in treatment. We
have learned much about breast cancer biology since this
time -- we now think that if tumors are detected when
small in size, they have not yet developed many blood
vessels, and are less likely to be aggressive or to metastasize.
Mammography can detect these small tumors and also can
detect the earliest form of breast cancer, called ductal
carcinoma in situ, and surgery can remove these lesions.
Olsen and Gotzscheís
analysis is not the first one to scrutinize the underlying
data in these studies. Other expert groups have conducted
intensive reviews of the studies and have reaffirmed previous
findings of a mortality reduction benefit,
the recent report of the USPSTF.
and consensus conferences have been convened in an attempt
to reach agreement on what the data actually say, and
we have all witnessed the difficulty and frustration that
ensue from these efforts to both reach agreement on the
meaning of the data and also to craft a statement that
accurately reflects the meaning. Simply put, this is not
an easy task, and the conclusions reached by Olsen and
Gotzsche are at variance with other reviews by expert
Cancer Institute has compiled a very comprehensive database
about cancer called Physician Data Query (PDQ), that contains
the latest available information about cancer prevention,
screening, diagnosis, treatment, genetics, supportive
care, and clinical trials. Independent PDQ advisory boards
have been retained by NCI to carry out periodic evaluations
of the body of scientific data and its usefulness for
drawing conclusions about the state of cancer care.
At its last meeting,
the PDQ screening and prevention editorial board discussed
The Lancet review and felt that Olsen and Gotzsche
made some valid points about the quality of the trials.
However, no modifications to the current PDQ statement
of evidence on breast cancer screening have been made
at this time; we expect that specific recommendations
will be discussed at the next meeting of the editorial
board in March 2002.
is NCI doing?
The NCI is committed
to improving health outcomes for women with breast cancer.
As part of the commitment, we will continue to strive
to monitor new information as it emerges and to communicate
what we learn. NCI has taken a number of steps to improve
our effectiveness in these areas. First, I have asked
two of NCIís division directors, Dr. Peter Greenwald,
Director of the Division of Cancer Prevention, and Dr.
Barbara Rimer, Director of the Division of Cancer Control
and Population Sciences, to lead the new NCI Breast Screening
Working Group. This group has three major tasks: one,
to monitor and evaluate new information on mammography
and how best to communicate the message; two, to monitor
NCIís research program on imaging and molecular technologies
for early detection; and three, to assess basic biology
as it pertains to early detection (for example, molecular
methods to differentiate indolent from aggressive tumors).
Second, NCI has
requested that the Institute of Medicine (IOM) review
the evidence related to mammography and advise us on their
interpretation of the evidence. This complements an ongoing
initiative of the IOM to periodically update their year
2000 report entitled, Mammography and Beyond. This
report examines the current state of the art in early
breast cancer detection, identifies promising new technologies,
and how best to move the field of breast cancer screening
Third, the NCI
Breast Cancer Surveillance Consortium (BCSC), a cooperative
agreement between the NCI and investigators at medical
research centers across the country, is evaluating the
performance of screening mammography in community practice
in the United States. This research collaboration links
data from mammography registries with data on cancer outcomes
from pathology laboratories or cancer registries. The
Consortium consists of eight research sites located in
seven states, plus a Statistical Coordinating Center.
As of April 2001, the Consortium's database contains information
on 2.2 million screening mammographic examinations and
28,000 breast cancer cases. This is a tremendous resource
that can tell us much more about how mammography is performed
in community practice.
The Breast Cancer
Surveillance Consortium supports a wide-ranging portfolio
of research projects that use population-based databases
to evaluate the performance of screening mammography in
community practice. Researchers at individual sites conduct
analyses using data collected at their sites. In addition,
all sites transmit their data to a centralized Statistical
Coordinating Center located at the Group Health Cooperative
site. This allows Consortium researchers to conduct analyses
across sites using pooled data.
Research in the
Consortium examines issues such as the effect of breast
density and hormone replacement therapy on the accuracy
of screening mammography, the relationship of mammography
assessment with final recommendations for diagnostic evaluation,
biologic characteristics of breast cancers detected by
mammography screening, and rates of detection of ductal
carcinoma in situ among screened women. Anticipating the
need to track the diffusion of new screening technologies
in clinical practice, the Consortium is developing measures
for tracking the use of digital mammography, which is
a promising emerging technology, and will serve as a model
for tracking the diffusion of other new technologies as
Data Support a Benefit for Mammography
In addition to
data from clinical trials, we also have data from our
population-based Surveillance, Epidemiology and End Results
(SEER) registries that can be used to track new cases
and deaths from breast cancer and to examine these in
relation to changes in mammography use over time. NCI
also has created a national collaboration of some of the
Nationís leading statisticians, called Cancer Intervention
and Surveillance modeling NETwork (CISNET), to examine
important questions about trends in breast cancer and
other diseases by using the latest modeling methods. Although
preliminary, recent work by the statisticians leads to
the following conclusion: breast cancer incidence rates
by stage showed a decline of later stage disease and larger
size tumors and an increase in smaller, early stage tumors
and pre-invasive cancers. Modeling this shifting of cases
to earlier tumors with better prognosis predicted a decline
in mortality during recent years, accounting for about
one-quarter to one-third of the observed decline in breast
cancer mortality since 1990. The important fact is that
back in the late 1980s, our statisticians predicted that
if mammography rose over the next decade, there would
be a subsequent decrease in mortality. We are now seeing
There is no doubt
that thousands of women are alive today because their
breast cancers were treated successfully after having
been detected by mammography. There also is no doubt that
we have plenty of opportunity for improvement. We need
better ways to detect breast cancer in its very earliest
stages and to prevent its further growth. While mammography
is the best technology we have available today, it has
limitations. Tumors that exist, especially in dense breast
tissue of younger women or located close to the chest
wall, may be missed (false negative), while in other women
there may be indications that cancer is present when it
is not actually present (false positive), leading to a
series of additional procedures such as repeat mammograms
and/or biopsies. The debate about the role of mammography
will continue until we have a better technology that more
accurately predicts a womanís risk of developing breast
cancer, and NCI is supporting a broad range of research
on promising new approaches to breast cancer screening
and early detection.
supported by NCI is advancing on several fronts.
Along with efforts to improve conventional and digital
x-ray mammography, NCI also supports research for several
other technologies such as magnetic resonance imaging
(MRI), ultrasonography, positron emission tomography (PET),
and single photon emission computed tomography (SPECT).
Already, with these technologies, scientists can "see"
and monitor biological processes taking place in living
tissues such as blood flow, oxygen consumption, and glucose
A major research
effort is under way to capitalize on the abundant discoveries
in cancer biology and create imaging technologies that
can noninvasively detect and display the actual molecular
events taking place in the body. Molecular
imaging will allow researchers to detect altered gene
products and tumor-specific receptors or enzymes.
The ability to visualize molecular pathways involved in
the development of tumors is expected to enable researchers
to detect and stage tumors more easily, to select more
effective treatments, and to predict the effectiveness
of new drugs. Some specific examples of research
supported by NCI:
- In 2001, the American College of Radiology Imaging
Network (ACRIN), a group of researchers sponsored by NCI,
launched the largest study ever to compare conventional
and digital mammography. The Digital
Mammographic Imaging Screening Trial (www.cancer.gov/templates/view_clinicaltrials.aspx?protocolNum=ACRIN-6652&version=healthcare+professional),
involving 49,500 women in the United States and Canada,
will compare digital mammography to standard film mammography
to determine how this new technique compares to the traditional
method of screening for breast cancer.
Imaging Ė MRI is an imaging modality making use of
a magnetic field and radio-wave signals linked to a computer
to create detailed images of areas inside the body without
the use of radiation. Each MRI produces hundreds of images
of the breast from side-to-side, top-to-bottom, and front-to-back.
A radiologist then interprets the images. Breast MRI is
not used for routine breast cancer screening, but clinical
trials are under way to determine whether MRI is valuable
for early detection in certain groups, such as young women
at high risk for breast cancer and women with a previous
history of breast cancer.
Tomography - PET creates computerized images of chemical
changes that take place in tissue. NCI-sponsored researchers
are evaluating the usefulness of PET to detect tumors
in dense breasts. A clinical trial is also evaluating
the usefulness of PET results compared with the findings
from other imaging and diagnostic techniques. This trial
is also studying the effectiveness of PET in tracking
the response of a tumor to treatment.
(CT) - Computed tomography creates a series of detailed
cross-sectional x-rays of areas inside the body taken
from different angles. The images are then turned into
two- and three-dimensional pictures by a computer program.
This technique is also called computerized tomography
(CT) and computerized axial tomography (CAT). Several
NCI-funded investigators are studying the use of dedicated
breast CT devices as both a screening and diagnostic tool
for the detection of breast cancer.
Spectroscopy (MRS) - MRS has the ability to distinguish
cancerous tissue from normal tissue and benign growths.
MRS can show the presence and relative quantities of the
chemicals comprising tissues of each type, and can characterize
even small tumors. As a result, MRS can make it easier
to detect breast cancer at even earlier stages. A number
of NCI grantees are exploring use of MRS in breast cancer.
- Optical imaging refers not only to the use of visible
light but also to radiation just beyond the visible --
ultraviolet and near-infrared. Several researchers are
evaluating the potential of using visible or near infrared
light to scan the breast for abnormalities alone and in
conjunction with other imaging technologies and the possibility
of combining such information with other techniques. For
example, NCI is supporting projects that superimpose optical
signals from small breast cancers onto MRI scans of the
Detection (CAD) - CAD involves the use of computers
to bring suspicious areas on a mammogram to the radiologistís
attention. Through a number of grants, NCI is funding
research that will develop computer-aided diagnosis methods
to assist radiologists in diagnosing breast cancer from
mammograms. It is hoped that CAD will improve radiologistsí
ability to interpret mammograms so that both the number
of missed cancers and the number of women unnecessarily
sent to biopsy can be reduced. A number of grantees are
exploring the use of CAD in breast cancer. Currently,
there are two FDA- approved CAD methods that are commercially
- The NCIís Development of Clinical Imaging Drugs
and Enhancers (DCIDE) program will foster
and speed the development of promising imaging agents,
such as contrast agents, and their translation from laboratory
to clinic. NCI will make its pre-clinical development
resources available to competitively selected developers
of a promising diagnostic agent or probe in order to remove
a recognized barrier between laboratory discoveries and
their entry into the clinic. To further aid in the development
of promising imaging agents, NCI is launching a program
to fund early clinical trials of novel imaging probes
and agents. One of the agents under development in this
program is a nanoparticle that specifically targets angiogenic
vessels. This could potentially play a role in cancer
detection, staging, and monitoring of therapy for breast
In addition to
imaging technology, NCI is investing in new biologic tests
to improve our ability to identify cancer cells in their
earliest possible stages of development. Among the research
Analysis - NCIís Innovative Molecular Analysis Technologies
Program (IMAT) supports the development of non-invasive
techniques for identifying molecular changes that distinguish
cancer cells from normal cells. More than 100 research
projects are under way, focusing on new approaches to
analyze DNA, RNA, and proteins.
Finding Protein Patterns - Proteomics is the systematic
study of protein expression and function. In the Clinical
Proteomics Program, a joint initiative of NCI and FDA,
researchers are discovering differences in patterns of
protein in the blood from cancer patients compared to
people without cancer and applying this knowledge to early
detection of breast cancer.
- NCIís Early Detection Research Network (EDRN) is the
first comprehensive network to develop and validate early
detection markers for cancer. Researchers are studying
a variety of molecules, proteins, genes, and other biological
substances that may be the earliest warning signs that
normal cells are on the road to becoming cancerous. Their
discoveries are then translated into methods for detecting
warning signals, sometimes even before full-blown cancer
of Cancer Cells: The Molecular Classification of Tumors
- All cells have unique "signatures" Ė special
characteristics related to which genes are active and
which proteins or other products the cell manufactures.
During the transformation of a normal cell to a cancer
cell, the cellís signature changes, and the change becomes
a signal of the presence of cancer. Researchers are developing
profiles of molecular alterations in human tumors, such
as breast cancer, using DNA, RNA, or protein-based technologies.
This technology holds promise for improving the early
detection, diagnosis, and treatment of cancer.
Over the years,
researchers have focused on examination of cells shed
by breast tissue into the ducts. Investigators have now
developed techniques for collecting nipple aspirates and
ductal lavage and hope that it may be possible to evaluate
suspicious breast masses detected by mammography by analyzing
these secretions. It may be possible to spare at least
some women the need to undergo a surgical biopsy.
These are by
no means established techniques, and it would be more
accurate to say that they are being "explored" rather
than "used" in breast cancer diagnosis. There are now
a number of investigators around the country who have
methods that enable them to collect these specimens, but
there is no consensus yet on how they should be analyzed.
The NCI is currently funding research through its exploratory
grant programs to determine which substances or characteristics
of cells present in these specimens will correlate reliably
with the presence of absence of cancer in the breast.
The research also includes development of new analytic
technologies to detect particular alterations. This research
has not yet progressed to a stage where large-scale clinical
trials are ready to proceed.
NCI also supports
a number of resources for the research community ranging
from tissue banks to registries to shared funding for
national monitoring programs.
It is not enough
to make discoveries. We also must turn those discoveries
into interventions that benefit people and communicate
that information so women can use it to make important
decisions about their health. The investments that NCI,
ACS, CDC, and AHRQ made in the 1980s and 1990s led to
effective interventions to enhance use of mammography.
There is a solid armamentarium of effective interventions,
and we have seen the former Black-white differences in
mammography use disappear. There still is under-use of
mammography among some groups, including older and Hispanic
women. We are now working with the CDC, ACS, and other
organizations to disseminate the effective interventions.
NCI has several
projects in place to improve the ways we communicate the
results of research and to take advantage of new communication
technologies. One example is a research project funded
by NCI and AHRQ studying how to communicate about the
benefits and limitations of screening tests. Researchers
are also developing tools to help women ask the important
questions and to examine their own preferences. These
research efforts are exploring the capacity of new communication
technologies, including online and other interactive health
communication tools, to address womenís questions.
come together in an equation that leads to longer and
better lives for breast cancer patients. All of our current
tools are important, and all must be improved because
the outcome, although better than in the past, is not
yet what it should be. We must retain what is adequate
and appropriate but strive to discover what is better.
Many of the new technologies now under development hold
real promise. Detecting the molecular changes that lead
to cancer will give us the opportunity to intervene in
the disease process more effectively. Like you, I am impatient
for these new approaches to prove themselves. The lives
of our mothers, daughters, wives, sisters, and friends
are at stake. We cannot allow ourselves to become complacent,
accepting the status quo. Yet, we must not ignore the
fact that our best available technology today, mammography,
does save lives.
I thank you for
this opportunity to testify about this vitally important
topic. I will be pleased to respond to your questions.
HHS Home (www.hhs.gov) |
Topics (www.hhs.gov/SiteMap.html) |
What's New (www.hhs.gov/about/index.html#topiclist) |
For Kids (www.hhs.gov/kids/) |
FAQs (answers.hhs.gov) |
Site Info (www.hhs.gov/SiteMap.html) |
Disclaimers (www.hhs.gov/Disclaimer.html) |
Privacy Notice (www.hhs.gov/Privacy.html) |
FOIA (www.hhs.gov/foia/) |
Accessibility (www.hhs.gov/Accessibility.html) |
Contact Us (www.hhs.gov/ContactUs.html)
revised: March 7, 2002