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Early mammography reduces breast cancer mortality with minor overdiagnosis rates
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Annual mammography screening of women aged 40 to 49 years corresponded with an early reduction in breast cancer mortality, according to the results of a randomized, controlled trial.
Further, cumulative incidence data indicated only a small volume of overdiagnosis occurred, according to the researchers.
“Although some service screening programs begin offering screening at age 40 or 45 years, most begin offering it from age 50 years,” Sue M. Moss, PhD, MSc, professor of cancer epidemiology at Queen Mary University of London’s Wolfson Institute, and colleagues wrote. “In England, the lower age limit for invitation is being reduced to 47 years, which means that when this extension is complete, all women will receive their first invitation before the age of 50 years.”
Moss and colleagues conducted the randomized, controlled U.K. Age trial to compare the effect of annual mammography beginning at age 40 or 50 years on breast cancer mortality.
The researchers randomly assigned 160,921 women aged 39 to 41 years from 23 U.K. National Health Service Breast Screening Programme units to an intervention group offered annual mammography up to and including age 48 years of age (n = 53,883) or the standard screening protocol of mammography commencement at age 50 years and every 3 years thereafter (n = 106,953).
Breast cancer mortality and total breast cancer incidence — including in-situ disease — served as the primary endpoints.
The median follow-up was 17.7 years (interquartile range, 16.8-18.8).
Overall, 594 breast cancer deaths occurred during the intervention phase and 757 occurred throughout the entire follow-up period.
A similar rate of breast cancer incidence occurred between both groups during follow-up (rate ratio [RR] = 0.98; 95% CI, 0.93-1.04).
The RR for all-cause mortality in the intervention group relative to the control group was 0.98 (95% CI, 0.93-1.03). However, when restricted to breast cancers diagnosed during the intervention phase, the RR was 0.88 (95% CI, 0.74-1.04). The absolute mortality reduction in the intervention group was 0.04 per 1,000 women-years or 0.47 per 1,000 women. These data equated to a number needed to screen of 1,366.
During the first 10 years following diagnosis, the intervention group experienced a significant reduction in breast cancer mortality compared with the control group (RR = 0.75; 95% CI, 0.58-0.97). However, the reduction did not persist thereafter for tumors diagnosed during the intervention phase (RR = 1.02; 95% CI, 0.8-1.3).
Cumulative incidence data indicate the absolute differences for in-situ and invasive cancer are equivalent to an additional 0.25 in-situ cancers and 0.93 fewer invasive breast cancers per 1,000 women invited for screening.
“Overall, these results support an early reduction mortality from breast cancer with annual mammography screening in women aged 40-49 years,” Moss and colleagues wrote. “Synthesis of results from all the trials, and further data from modern service screening might clarify long-term effects. Cumulative incidence figures suggest at worst a small amount of overdiagnosis.”
Several limitations should be acknowledged when interpreting these findings, Daniel B. Kopans, MD, professor of radiology at Harvard Medical School and director of breast imaging at Massachusetts General Hospital, wrote in an accompanying editorial.
“Despite the fact that radiation risk to the breast for women aged 40 years and older is very low, concerns about radiation exposure lead the U.K. Age trial investigators to use a single view (mediolateral oblique) for incidence screening instead of the two views used in the U.S.,” Kopans wrote. “In the U.K., investigators have shown that using only the projection meant that the screening probably missed 25% of early breast cancers. Moreover, by not taking biopsy samples of clustered microcalcifications when 18% of small invasive cancers are detected by the presence of these calcifications in their in situ component, the investigators in the U.K. Age trial missed additional early cancers.”
Despite the limitations, the study findings hold potentially important practice information, Kopans wrote.
“No scientific evidence exists for a screening threshold at the age of 50 years, and women and their physicians should not be misled,” Kopans wrote. “Although the U.K. Age trial arose to address concerns related to the interpretation of incomplete data, it confirmed the fact that screening women in their forties saves lives. Had both screening views been used, and had clustered classifications been biopsied, the U.K. Age trial would have probably shown a much larger decrease in deaths in the intervention group.” – by Cameron Kelsall
Disclosure: Moss reports research funding from American Cancer Society, Cancer Research U.K., Department of Health, Medical Research Council, the NIH Research Health Technology Assessment and the U.S. NCI. The other researchers and Kopans report no relevant financial disclosures.
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