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Answer to debate over mammography likely found ‘somewhere in the middle’
Discrepant reports about the benefits and harms of screening mammography have sparked vigorous debate among experts, creating controversy that has left many women feeling confused about whether they should continue to participate in mammography programs for breast cancer screening at all.
In 2009, the US Preventive Services Task Force (USPSTF) recommended that patients delay screening mammography to age 50 and decrease frequency of mammography screening to every 2 years. However, many states have recently passed breast density notification laws that require radiologists to notify patients about dense breast tissue (an incredibly common condition amongst women) and its tendency to obscure cancers on mammogram, as well as to discuss what screening options should therefore be undertaken. Such laws undoubtedly will lead to increased breast cancer screening for many women, often with supplemental tests such as ultrasound and/or tomosynthesis. Our patients are, therefore, receiving mixed messages.
Breast cancer mortality in the United States has fallen by 30% during the past 20 years, and great debate exists whether this is due to better treatment, earlier detection through screening, or a combination of both. There are nine well-recognized randomized, controlled trials of mammography screening in more than 600,000 women frequently referenced, and meta-analyses of these individual trials consistently report about a 20% reduction in breast cancer mortality with the use of screening mammography.
Rachel C. Jankowitz
Adam M. Brufsky
The Canadian National Breast Screening Study — a very large study of almost 90,000 women randomly assigned to either mammography or physical exam — stands out as one of only two of the nine trials that has not shown a breast cancer mortality benefit with mammography screening. Results showed 180 breast cancer-related deaths (27%) occurring in 666 women diagnosed with breast cancer in the mammography arm, and 171 breast cancer-related deaths (32.6%) occurring in 524 women diagnosed with breast cancer in the control arm.
In the accompanying editorial, Kalager and Bretthauer postulate that the failure of the Canadian trial to show a benefit to screening mammography was likely due to systemic adjuvant therapy and education of the participating women on the self-breast physical examination. They raise the same question asked by Gilbert Welch, MD, at the San Antonio Breast Cancer Symposium in 2013: “Does screening become less effective as treatment gets more effective?” They point to the 22% rate for overdiagnosis seen in the Canadian trial and agree with the authors’ assertion that mammography screening recommendations need to be “urgently reassessed by policy makers.”
In contrast, Robert A. Smith, PhD, senior director of cancer screening at the American Cancer Society, gave a very nice overview of four of the most commonly discussed recent analyses of mammography benefits: the 2012 UK Independent Breast Screening Review, the 2009 USPTF review, the 2011 Nordic Cochrane review and the 2012 European Screening Network (EUROSCREEN) review. Amazingly, these four reports varied 20-fold in their reported number needed to screen to prevent one breast cancer-related death (range, 111 to 2,000).
Smith’s team sought to understand why such discrepancies existed in reporting this seemingly simple number. Ultimately, they found that some studies reported “number needed to screen,” meaning it included women who actually participated in mammography screening, and other studies reported the “number needed to invite to screening.” Moreover, length of follow-up varied across these four reports, as did the age of the included women.
When Smith and colleagues converted the data across these four studies and reported the number needed to screen within the framework of a standardized scenario — which examined the effect of screening for 20 years, from age 50 to 69 years — the 20-fold variation in the number needed to screen to prevent one breast cancer death dropped to a 2.5-fold difference across the four studies, from a range of 111 to 2,000 women to a range of 96 to 257 women needed to screen to save one life.
The rates for overdiagnosis across the four trials also varied widely, from 1 to 10 (6.5% to 30%) women overdiagnosed to prevent one death. Smith asserted that overdiagnosis rates must be corrected by incidence trends and lead time bias in order to reduce the variation in these reported rates.
There is no doubt that screening mammography has limitations. As with any large population screening test, screening must involve many to save few. False positives are a major problem, especially for younger women, and at least 300 women out of 1,000 women screened in the United States during a 10-year time period can expect to have one false-positive result.
Overdiagnosis will occur in a certain percentage of women, but the reported percentage of women overdiagnosed varies from 0% to 50% in the literature, with intense arguments about adjustments for varying incidence rates over time and lead time bias underlying this broadly reported range.
Our opinion is that, when a case can be argued so eloquently on either side, the answer likely lies somewhere in the middle: The decrease in breast cancer mortality is likely due to a combination of early detection with screening and better systemic therapy.
The Canadian trial results cannot be ignored, and further work is needed to define the potential benefits and risks of mammography to individual patients. It makes sense to us that standardized reporting of absolute benefits of a screening mammography program — in terms of number needed to screen vs. number needed to invite to screening, patient population, and length of follow-up — should be employed when comparing results across individual trials.
In the meantime, we should discuss with our patients the potential benefits and risks of screening mammography using the best information we have available to us at this time from across all of the trials, rather than focusing on one individual trial. Trials of screening mammography have shown consistently a 20% reduction in breast cancer mortality but at the expense of false positives, which can have long-term psychosocial consequences, according to some reports. We also advocate assessing risk factors for breast cancer when having this discussion with individual patients, so as not to overlook patients who may benefit most from early detection.
References:
Kalager M. BMJ. 2014;doi:10.1136/bmj.g1403.
Miller AB. BMJ. 2014;doi:10.1136/bmj.g366.
Smith RA. Abstract #S1-10. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2013; San Antonio.
US Preventive Services Task Force. Ann Intern Med. 2009;151:716-726.
For more information:
Rachel C. Jankowitz, MD, is assistant professor of medicine at the University of Pittsburgh Cancer Institute, and a medical oncologist at UPMC Cancer Center and Magee-Womens Hospital of UPMC.
Adam M. Brufsky, MD, PhD, FACP, is professor of medicine at the University of Pittsburgh School of Medicine, associate chief of the division of hematology/oncology at the University of Pittsburgh School of Medicine’s department of medicine, and co-director of the Comprehensive Breast Cancer Center at the University of Pittsburgh Cancer Institute. Brufsky also is a HemOnc Today Editorial Board member.
Disclosure: Brufsky and Jankowitz report no relevant financial disclosures.