Screening mammography leads to overdiagnosis of small breast tumors
The routine use of screening mammography has resulted in the increased diagnosis of small breast tumors and a decreasing incidence in large tumors, according to observational study results published in The New England Journal of Medicine.
However, this diagnostic shift more likely represents overdiagnosis of small tumors than early detection of malignant tumors, and likely has not contributed to reduced breast cancer mortality, according to the researchers.
Screening mammography is intended to diagnose asymptomatic small malignant tumors. Effective routine screening should result in the greater detection of small tumors, thereby reducing the rate of large tumors.
“Although the biologic characteristics of a tumor are now recognized to be more relevant to breast cancer prognosis than the size of the tumor, tumor size is more relevant to the assessment of the proximate effect of screening,” H. Gilbert Welch, MD, MPH, professor of medicine at The Dartmouth Institute for Health Policy and Clinical Research, and colleagues wrote. “Screening mammography is not an assessment of functional gene expression; rather, it is an anatomy-based search for small structural abnormalities that are too small to be felt. Thus, the ultimate goal of reduced cancer-specific mortality must be mediated through tumor size at diagnosis.”
Welch and colleagues accessed the SEER database to determine tumor size distributions and size-specific breast cancer incidence among women aged 40 years or older between 1975 and 2012.
Researchers calculated the 10-year risk for breast cancer–specific death by tumor size in two time periods: 1975 through 1979, prior to the widespread implementation of screening mammography; and 2000 through 2002, the most recent period with available 10-year follow-up data.
The researchers found that the size distribution of tumors detected correlated with the widespread availability of mammography screening.
The proportion of smaller tumors — which included in-situ carcinomas or invasive carcinomas measuring smaller than 2 cm — increased from 36% to 68% between 1975 and 2012. However, the incidence of larger tumors, or invasive tumors measuring 2 cm or larger, decreased from 64% to 32%.
The researchers attributed this shift in distribution to a significant increase in smaller tumor detection, rather than a decrease in larger tumors. Larger tumors decreased by 30 cases per 100,000 women, whereas smaller tumors increased by 162 cases per 100,000 women.
“Assuming that the underlying burden of clinically meaningful breast cancer was unchanged, these data suggest that 30 cases of cancer per 100,000 women were destined to become large but were detected earlier, and the remaining 132 cases of cancer per 100,000 women were overdiagnosed,” Welch and colleagues wrote.
Size-specific fatality rates declined during both study periods. The researchers credited improvements to systemic therapy with the decreased mortality associated with large tumors.
“For small tumors, however, the declining case fatality rate was biased by the combined effect of lead time, length and overdiagnosis,” Welch and colleagues wrote. “In fact, during the period from 2000 to 2002, women with in-situ carcinomas or those with invasive tumors measuring less than 1 cm had 10-year survival rates that exceeded 100% — meaning that they were more likely than age-matched women in the general population to survive.”
The researchers compared the reduction in mortality due to screening in the current study period with the previous study period, in which different therapies were used. The previous era resulted in a reduction of 12 deaths per 100,000 women by mammography, compared with approximately eight deaths per 100,000 women in the current period. Based on these data, researchers calculated that improved treatment contributed to at least two-thirds of the declines in breast cancer mortality.
“There is no perfectly precise method to assess the population effects of cancer screening,” Welch and colleagues wrote. “Screening mammography performed in an asymptomatic population that has an average risk for cancer can, at best, have only a small absolute effect on cancer-specific mortality because the vast majority of women are not destined to die of this target cancer. ... We do not pretend to present a precise estimate of either the amount of overdiagnosis or the contribution of screening mammography to the reduction in breast cancer mortality. The data regarding size-specific incidence, however, make clear that the magnitude of overdiagnosis is larger than is generally recognized.”
Curbing overdiagnosis will require a reevaluation of how cancer should be approached and treated, Joann G. Elmore, MD, MPH, professor of medicine and adjunct professor of epidemiology at University of Washington School of Medicine, wrote in an accompanying editorial.
“The threat of medical malpractice litigation coupled with financial incentives to do more can conflict with our goal of helping patients,” Elmore wrote. “We get credit for curing disease that would never have harmed the patient. We receive positive feedback from patients thanking us for ‘saving my life,’ alarming feedback from patients with ‘missed diagnoses,’ and no feedback at all from patients whose cancer was overdiagnosed. The mantras ‘all cancers are life-threatening’ and ‘when in doubt, cut it out’ require revision.”
Patients may require greater education on overdiagnosis, as well.
“We must improve communication regarding overdiagnosis at all levels, from dissemination of scientific findings at a population level to education of patients before they undergo screening,” Elmore wrote. “Clinicians face time constraints and lack experience in communicating screening nuances. Better training may help. Building trust in science and medicine starts by taking ownership of all aspects of the screening cascade, including the collateral damage of our well-intentioned efforts.” – by Cameron Kelsall
Disclosures: Welch reports personal fees from Beacon Press outside the submitted work. The other researchers report no relevant financial disclosures. Elmore reports personal fees from Healthwise/Informed Medical Decisions Foundation and UpToDate outside the submitted work.