April 2, 2012 — Mammography screening is linked to overdiagnosis of
breast cancer, according to findings from the Norwegian Screening
Program reported in the April 3 issue of the Annals of Internal Medicine.
The investigators suggest that overdiagnosis not only poses a
significant ethical dilemma but also burdens the patient and the
healthcare system.
"Mammography screening increases breast cancer incidence owing to
earlier detection of cancer that would otherwise have been diagnosed
later in life and to overdiagnosis of cancer that would not have been
identified clinically in a lifetime," write Mette Kalager, MD, from the
Harvard School of Public Health, Brigham and Women's Hospital, Boston,
Massachusetts, and colleagues. "Overdiagnosis can theoretically occur
because the tumor lacks potential to progress to a clinical stage or
because the woman dies of other causes before the breast cancer surfaces
clinically.... In both instances, however, the woman would be diagnosed
and treated with no possible survival benefit."
The goal of this study was to estimate the percentage of
overdiagnosis of breast cancer attributable to mammography screening,
defined as the percentage of cases of cancer that would not have become
clinically evident during a woman's lifetime without screening. The
investigators note that the absence of valid comparison groups
previously hindered achievement of this goal, because incidence trends
attributable to screening could not be distinguished from temporal
trends in incidence.
Norway gradually implemented the nationwide mammography screening
program, the Norwegian Screening Program, from 1996 to 2005 by inviting
women aged from 50 to 69 years to participate. The investigators
compared concurrent incidence of invasive breast cancer from 1996 to
2005 in counties that had already implemented the screening program with
that in counties that had not yet implemented the program. They also
assessed incidence rates during the preceding decade, which allowed
adjustment for changes in temporal trends in breast cancer incidence.
The first approach to calculating the percentage of overdiagnosis was
to account for the expected decrease in incidence after cessation of
screening after 69 years of age. The second approach was to compare
incidence in the current screening group with incidence among women 2
and 5 years older in the historical screening groups, accounting for
average lead time.
Of 39,888 patients diagnosed with invasive breast cancer, 7793
received their diagnosis after implementation of the screening program.
For approach 1, the estimated rate of overdiagnosis associated with the
program was 18% to 25%, and for approach 2, it was 15% to 20% (P
< .001 for both approaches). Assuming overdiagnosis of 15% to 25% of
cases of cancer, 6 to 10 women would be overdiagnosed for every 2500
women invited for screening.
Limitations of this study include a reliance on registry-based
participants and data, possible unmeasured confounding, a lack of data
on ductal carcinoma in situ, and that the duration of follow-up may have
been insufficient after introduction of screening in some areas to
allow stable estimates of the degree of overdiagnosis.
"Mammography screening entails a substantial amount of overdiagnosis," the study authors write.
Overdiagnosis More Likely in United States Than in Europe
In an accompanying editorial, Joann G. Elmore, MD, MPH, from the
University of Washington School of Medicine in Seattle, and Suzanne W.
Fletcher, MD, from Harvard Medical School and Harvard Pilgrim Health
Care Institute in Boston, Massachusetts, note that the Norwegian
estimates of overdiagnosis may not apply to the United States.
Overdiagnosis is probably even more common in the United States than in
Norway, because US radiologists are more likely than European
radiologists to report mammographic abnormalities, and because US women
often start annual mammography screening at 40 years of age, whereas
Norwegian women start biennial screening at 50 years of age.
"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 cannot wait for these
tools to be developed," Dr. Elmore and Dr. Fletcher write. "Evaluating
strategies for observing change in some lesions over time instead of
recommending an immediate biopsy has been suggested. 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."
The editorialists also point out that overdiagnosis will probably
increase as breast magnetic resonance imaging and other newer imaging
modalities are introduced.
"Finally, we have an ethical responsibility to alert women to this
phenomenon," the editorialists conclude. "Most patient-education aids do
not even mention overdiagnosis, and most women are not aware of its
possibility. Effective communication about overdiagnosis of breast
cancer will require great care — and evaluation to determine how best to
do it; otherwise, women may become fearful or angry."
The Norwegian Research Council and Frontier
Science funded this study. The authors have disclosed no relevant
financial relationships. Dr. Elmore serves as the medical editor for the
patient education materials for the Foundation for Informed Medical
Decisions. Dr. Fletcher has received payment for lectures, including
service on speakers bureaus, from the Lance Armstrong Foundation
Distinguished Professor of Cancer Research and the Society of General
Internal Medicine; has received royalties from Kluwer; and received
payment for development of educational presentations and travel,
accommodations, or meeting expenses from the Melanoma Research Alliance
Team Award 2010-2011 and the Melanoma Research Alliance Annual Retreat,
2010-2012.
Ann Intern Med. 2012;156:536-537.
