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Mammography screening associated with increase in small breast cancers
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Mammography screening has led to increased detection of small breast cancers without a concomitant decline in the detection of larger breast cancers or breast cancer mortality, according to the results of a county-based ecological SEER analysis.
These findings suggest mammography screening has led to the overdiagnosis of breast cancer, according to the researchers.
“The goal of screening mammography is to reduce breast cancer mortality by detecting and treating cancer early in the course of the disease,” Richard Wilson, DPhil, of the department of physics at Harvard University, and colleagues wrote. “The associations between screening, incidence, mortality and tumor size can be investigated at the population level by comparing areas of the U.S. that have different rates of screening.”
Wilson and colleagues identified 16 million women aged 40 years or older who resided in 547 U.S. counties in 2000 using SEER cancer registries. All women received a mammogram within the previous 2 years.
Researchers sought to define the incidence of breast cancer in 2000 and incidence-based mortality — age adjusted to the U.S. population — during follow-up for each county.
Follow-up for women who received a breast cancer diagnosis (n = 53,207) continued through 2010.
The extent of breast cancer screening positively correlated with breast cancer incidence across U.S. counties (weighted r = 0.54; P < .001). However, researchers identified no association between 10-year breast cancer mortality and extent of screening (weighted r = 0.00).
An absolute increase of 10 percentage points in the extent of screening at the county level increased breast cancer diagnoses 16% (RR = 1.16; 95% CI, 1.13-1.19), which equated to 35 to 49 cases per 100,000 women as an absolute difference. However, the increase in screening did not change the rate for 10-year breast cancer mortality (RR = 1.01; 95% CI, 0.96-1.06).
Results of an analysis stratified by tumor size indicated a 10-percentage point increase in screening resulted in a 25% increase in the incidence of small (≤ 2 cm) breast cancers (RR = 1.25; 95% CI, 1.18-1.32) and a 7% increase in the incidence of larger (˃ 2 cm) breast cancers (RR = 1.07; 95% CI, 1.02-1.12).
Further, a 10-percentage point increase in screening rates correlated with an increase in early-stage breast cancer (stage 0-11; RR = 1.22; 95% CI, 1.17-1.28) but not advanced and metastatic breast cancer (stage III-IV; RR = 1.02; 95% CI, 0.97-1.07).
A 10-percentage point increase in screening also increased the occurrence of breast-conserving surgical procedures (RR = 1.24; 95% CI, 1.15-1.34). The researchers observed no related reduction in non–breast-conserving procedures, such as total or radical mastectomy.
“Our analysis shows that, when directed toward the general U.S. population, the most prominent effect of screening mammography is overdiagnosis,” Wilson and colleagues concluded. “Nonetheless, we do not believe that the right rate of screening mammography is zero. As is the case with screening in general, the balance of benefits and harms is likely to be most favorable when screening is directed to those at high risk, provided neither too frequently or too rarely and sometimes followed by watchful waiting instead of immediate active treatment.”
Joann G. Elmore
The nature of ecological studies may present potential limitations of these results, Joann G. Elmore, MD, MPH, professor of medicine and adjunct professor of epidemiology at University of Washington, and Ruth Etzioni, PhD, biostatistics researcher in the division of public health sciences at Fred Hutchinson Cancer Center, wrote in an accompanying editorial.
“It is well known, for example, that ecological studies provide no information as to whether the people who were actually exposed to the intervention were the same people who developed the disease, whether the exposure or the onset of disease came first, or whether there are other explanations for the observed association,” Elmore and Etzioni wrote. “Ecological analyses also may not properly reflect group-level associations because of area-level variations in confounding factors or other practices affecting the outcome.”
It is important for doctors to effectively communicate information regarding mammography to patients, Elmore and Etzioni concluded.
“We need clear communication and better tools to help women make informed decisions regarding breast cancer screening mammography,” they wrote. “We need to learn how to communicate with our patients about uncertainty and the limits of our scientific knowledge. In the end, we all need to become comfortable with informing women that we do not know the actual magnitude of overdiagnosis with precision. Part of informed decision making is providing all the information, even our uncertainty.” – by Cameron Kelsall
Disclosure: Wilson reports no relevant financial disclosures. Other researchers report research funding from and leadership roles with Exergen Corp. Elmore reports a medical editor role with Informed Medical Decisions Foundation.
Perspective
Back to TopKathryn Evers , MD, FACR
This paper is an ecological study of two pooled large data sources investigating the incidence and mortality of breast cancer and how it is affected by the overall use of mammography. Not surprisingly, the authors found an increased incidence of breast cancer in those counties where there was a greater use of mammography. No such correlation with mortality from breast cancer was observed. Furthermore, an increase in the detection of small (<2cm) tumors was not accompanied by a decrease in the number of large (>2cm) tumors detected.
The authors conclude from this data that screening mammography results mainly in overdiagnosis of breast cancer. While there is undoubtedly some overdiagnosis and accompanying overtreatment of breast carcinoma — especially of low-grade DCIS — their conclusion that mammography does not reduce breast cancer mortality is at odds with multiple earlier studies.
As is elucidated in the invited commentary, although the results are intriguing, there are problems with studies of this type. There is no way of knowing if the individuals who were screened were the same individuals who developed cancer. The use of self-reporting of mammogram behavior is also problematic, as accuracy is always questionable. Follow-up data of 13 years is probably not sufficiently long to capture the value of mammography screening, as has been demonstrated in previous randomly controlled trials.
It is also difficult to evaluate breast cancer as a single disease, especially as diagnosis and treatment is becoming increasingly individualized and sophisticated. There are clearly many diagnosed breast cancers that are overtreated, especially low-grade DCIS. Unfortunately, we have not progressed to a point where we have enough certainty about tumor behavior to modify standard treatment regimens. When that point is reached, changes in radiologic and pathologic diagnoses can be modified to more accurately reflect the individual patient’s prognosis.
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