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Overdiagnosis in Breast Cancer Screening: Time to Tackle an
Underappreciated Harm
The earlier that cancer is found, the better. This under-
lying tenet of cancer screening has saved many lives.
However, studies are beginning to challenge the certainty
that finding cancer early is always better. One stark exam-
ple was the practice of screening infants for neuroblastoma.
After the introduction of a simple urine test in Japan led to
nationwide screening, the incidence of neuroblastoma ap-
proximately doubled, whereas that of mortality and late-
stage disease remained unaffected. Widespread urine test-
ing of infants was subsequently abandoned (1). The excess
cases of cancer found on screening were examples of over-
diagnosis, defined as occurring when “a condition is diag-
nosed that would otherwise not go on to cause symptoms or
death” (2). Overdiagnosis need not imply that a given screen-
ing effort is ineffective or ill-advised. Indeed, overdiagnosis has
been documented in effective screening programs for several
types of cancer, including breast cancer.
Pathologically diagnosed breast cancer is heteroge-
neous; whereas some tumors grow rapidly, others grow
slowly, and still others may never grow. Tumors that grow
slowly or not at all can lead to overdiagnosis. Unfortu-
nately, mammography screening programs cannot distin-
guish between fatal and harmless breast cancer. Breast can-
cer overdiagnosis can only harm the affected woman.
Whereas other harms of breast cancer screening, such as
pain from compression of the breasts during examination
or anxiety due to false-positive results, are transitory, the
impact of a cancer diagnosis lasts a lifetime.
Reported estimates of breast cancer overdiagnosis
range from 0% to 54%, highlighting the complexity of this
topic (3–8). Long-term follow-up of women in random-
ized trials provide some estimates. For example, in the
Malmo¨ randomized, controlled trial (3), the total number
of diagnosed invasive breast cancer remained higher in the
screened group than in the control group after 15 years of
follow-up, a persistent excess of 115 cases. A spike in breast
cancer incidence would be expected early in the screening
group, but the number of cases in the control group should
“catch up” over time if no overdiagnosis occurred.
Population-level cancer registries offer another approach,
tracking the incidence of breast cancer before and after
screening is introduced. However, changes other than the
introduction of screening might influence breast cancer in-
cidence. Estimates of overdiagnosis tend to be higher when
studies use a denominator that is restricted to only
screening-detected cancer (because overdiagnosis can occur
only in this subset), include ductal carcinoma in situ cases
as well as invasive cancer, involve shorter follow-up, or
include control groups that have little or no access to
screening.
Kalager and colleagues’ study (9) in this issue adds
valuable data by presenting a population-based trial that
describes the incidence of invasive breast cancer in Nor-
way; the authors took advantage of the fact that breast
cancer screening was gradually introduced in different geo-
graphic areas of the country between 1996 and 2005. Stag-
gered introduction enabled comparison of both concurrent
and historical trends in breast cancer incidence and allowed
comparison of regions with and without mammography
screening. The study included 39 888 patients with inva-
sive breast cancer, of whom almost 8000 were diagnosed
after the introduction of routine screening. Overall, Kal-
ager and colleagues estimated that 15% to 25% of the cases
diagnosed in the screening areas represented overdiagnosis
(9). Their estimates varied depending on the length of
follow-up and were calculated from a denominator that
included all cases of cancer, not just those detected by
screening.
Strengths of the study include the high attendance rate
(77%) of women in the screening program and the re-
ported low rate of mammography in areas where the
screening program had not yet been introduced. However,
because the study was not a randomized trial, women in
the various regions may have differed in ways other than
breast cancer screening; the authors point out that different
regions of Norway varied in breast cancer incidence rates
and temporal trends. The study is also limited in that the
follow-up after introduction of screening in some areas
may not have been long enough to allow stable estimates of
the degree of overdiagnosis.
Two factors suggest that estimates of overdiagnosis
from Norway may not generalize to the United States.
First, U.S. radiologists are more likely than their European
counterparts to report abnormalities found on mammo-
grams (10, 11). Second, U.S. women often start annual
mammography screening at age 40 years, whereas Norwe-
gian women start biennial screening at age 50 years. Given
more frequent screening over a longer time, overdiagnosis
probably occurs more often in the United States than in
Norway.
Instead of focusing on the exact extent of overdiagno-
sis, it is time to agree that any amount of overdiagnosis is
serious and to start dealing with this issue now. Ultimately,
better tools are needed to reliably identify which breast
cancer will be fatal without treatment and which can be
safely observed over time without intervention, but we can-
not wait for these tools to be developed. Mammographers,
especially those in the United States, could help by consid-
ering changes in the threshold for calling a mammographic
feature abnormal. Evaluating strategies for observing
change in some lesions over time instead of recommending
Annals of Internal MedicineEditorial
536 © 2012 American College of Physicians
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an immediate biopsy has been suggested (10, 12, 13). This
may be a tough sell for women with anxiety as a result of
the “watch-and-wait” approach, as well as for radiologists
who do not want to miss any sign of disease and fear
malpractice lawsuits. Nevertheless, unless serious efforts are
made to reduce the frequency of overdiagnosis, the prob-
lem will probably increase as newer imaging modalities,
such as breast magnetic resonance imaging, are introduced.
Finally, we have an ethical responsibility to alert
women to this phenomenon. Most patient-education aids
do not even mention overdiagnosis (14), and most women
are not aware of its possibility (15). Effective communica-
tion about overdiagnosis of breast cancer will require great
care—and evaluation to determine how best to do it; oth-
erwise, women may become fearful or angry. Just because
communicating with patients will be difficult does not mean
that we should not tackle this problem. Informed women
deserve no less when deciding about breast cancer screening.
Joann G. Elmore, MD, MPH
University of Washington School of Medicine
Seattle, WA 98104-2499
Suzanne W. Fletcher, MD
Harvard Medical School and Harvard Pilgrim Health Care
Institute
Boston, MA 02215
Potential Conflicts of Interest: Disclosures can be viewed at www
.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum⫽M12
-0505.
Requests for Single Reprints: Joann G. Elmore, MD, MPH, 325
Ninth Avenue, Room 10EH03, Box 359780, Seattle, WA 98104-2499.
Current author addresses are available at www.annals.org.
Ann Intern Med. 2012;156:536-537.
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EditorialOverdiagnosis in Breast Cancer Screening
www.annals.org 3 April 2012 Annals of Internal Medicine Volume 156 • Number 7 537
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Current Author Addresses: Dr. Elmore: 325 Ninth Avenue, Room
10EH03, Box 359780, Seattle, WA 98104-2499.
Dr. Fletcher: 208 Boulder Bluff, Chapel Hill, NC 27516.
Annals of Internal Medicine
W-174 3 April 2012 Annals of Internal Medicine Volume 156 • Number 7 www.annals.org
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