Breast Cancer Screening: A Final Analysis?
Authors: J. E. Garber
Journal: CA A Cancer Journal for Clinicians (2003)

After 40 years and the participation of hundreds of thousands of women for decades of follow-up in randomized breast cancer screening trials, have we at last come to clear conclusions and policies regarding breast cancer screening? It appears that uniform and permanent international agreement on screening may not be possible regarding the ages at which to begin and stop, the role of breast examinations—both clinical and self-examination—screening interval and, of course, new technologies as they are introduced. In addition, any modifications of screening recommendations for specific risk categories will require prospective evaluation. However, with this set of updated Guidelines for Breast Cancer Screening the American Cancer Society (ACS) has provided a set of assessments and recommendations that are unambiguously stated, with thoughtful, reasoned summaries of the supporting data and clear indications of areas for which sufficient supporting data are lacking.1 In addition, as befits leaders in this field, they have pushed these guidelines further in two important ways. First, for the first time, the guidelines address the status of the breast cancer screening modality data for women with very high breast cancer risk. Secondly, they have begun to develop standards by which new technologies should be evaluated in order to be accepted as screening tools for usual-risk women. It seems that breast cancer screening frequently engenders controversy followed by statements and guidelines whenever a pertinent new study appears. In 1997, the National Institutes of Health (NIH) Consensus Conference was unable to reach consensus; so they crafted a remarkable statement in which mammographic screening for women aged 40 to 49 years was left to the discretion of women and their physicians.2 The acrimony and outcry in the breast cancer community was intense. The ACS navigated this controversy by publishing an assessment of the issues in which they strongly endorsed the value of screening mammography for this group, while emphasizing the need for discussion of the risks and benefits of the procedure.3 In 2000, Gøtzsche and Olsen published their controversial paper questioning the value of mammographic screening in general. They declared that six of eight randomized clinical trials were so methodologically flawed as to justify their exclusion from any serious analysis.4 The two trials they considered adequate found no effect of screening on breast cancer mortality. They concluded that there was no reliable evidence that screening decreases breast cancer mortality in any group. Their conclusions galvanized the community to reevaluate the data once again. Swedish investigators published an overview of their four clinical trials in which they argued against the criticisms of their trials by Gøtzsche and Olsen, and estimated a 21% reduction in breast cancer mortality persisting for a median of 15.8 years.5 The International Agency for Cancer Research (IARC) convened a working group, which assessed seven trials. They concluded that most of the criticisms raised by Gøtzsche and Olsen were unfounded, and that, in any case, they did not invalidate the evidence for a reduction in breast cancer mortality by screening approximating 35 percent for women aged 50 to 69. The evidence was more limited for women aged 40 to 49 years.6 The reports of the US Preventive Services Task Force (USPSTF), another independent panel convened to review various important issues in health care, are supportive of screening and discussed below. Finally, a Global Summit on Mammographic Screening was held in Milan in June 2002 in association with several international groups, including the ACS. The Summit participants reviewed data from not only the randomized trials but also 14 established mammographic screening programs, and concluded that mammographic screening was, in fact, effective in reducing breast cancer mortality but that it was only a single component of breast cancer screening.6 The components of breast cancer screening are addressed separately in the current ACS Guidelines. Perhaps because of the costs involved, most of the controversy has focused on mammographic screening. However, the roles of clinical and self-breast examination are also examined in depth, and are addressed in the Guidelines as well. The evidence that high-quality mammo-grams reduce breast cancer mortality in women aged 50 to 69 is considerable. In their most recent meta-analysis, the USPSTF summary relative risk among screened women aged 50 or older was 0.78 (95% CI 0.70 to 0.87) after 14 years of observation, with a number needed to screen of 838 (95% CI, 494 to 1,676) to prevent one breast cancer death. The benefits of screening appear to increase with age, though older women are less willing to attend screening.7 Recommendations for mammographic screening in younger women aged 40 to 49 years at initiation have been the source of most of the controversy. The potential importance of this issue is illustrated by the following calculation. It has been estimated that over 40 percent of the years of life lost to breast cancer diagnosed before age 80 years is attributable to cases presenting symptomatically at ages 35 to 49 years.6 The difficulty in establishing the benefit of screening mammography in younger women has been attributed to both the technical limitations introduced by their generally increased breast parenchymal density8 and to differences in breast cancer biology in younger women. The ACS has consistently endorsed regular mammographic screening for women aged 40 to 49, first in their published recom-mendations in July 1983 and now again in the 2003 document. Five of the seven randomized controlled trials that included women aged 40 to 49 years at entry have now demonstrated a risk reduction for this group of women, while two trials (the Stockholm and Canadian trials) have not. In the independent meta-analysis performed recently by the USPSTF, which excluded only the Edinburgh trial on methodologic grounds, the summary relative risk was 0.85 (CI 0.73-0.99) after 14 years of observation. These data as well as the interpretation of the data summarized in the ACS statement should increase the confidence with which screening recommendations can be extended to include women in this younger age group. The ACS Guidelines also deal carefully with the issues for which considerably fewer conclusive data are available, such as psychological harm from false-positive mammograms and their requisite additional evaluations as well as the potential overtreatment of ductal carcinoma in situ.9 Without uniform agreement among panel members, the statement ultimately recommends both regular clinical breast examination as well as continued teaching of breast self-examination, while acknowledging that the benefits of these strategies are unclear at this time. The justification for this position is laid out in the discussion with a call for additional research. Despite the demographic and economic challenges posed by the aging of the population and the increasing incidence of breast cancer with age, the Guidelines call for continued screening in older women who have few competing causes of mortality and who would be candidates for treatment if breast cancer were identified. This position is again clearly justified in the document, which reminds readers that since average life expectancy after age 70 is more than 15 years and since the elderly are diverse with regard to health status, chronological age alone may be a difficult way to determine the utility of screening procedures, and that competing causes of mortality as well as other factors should perhaps also influence future recom-mendations. Finally, these new ACS Guidelines contain an innovative section on early detection of breast cancer in women at increased risk. The High-Risk Work Group includes many recognized experts who participated in the Cancer Genetics Study Consortium expert panel who addressed this issue in 1997.10 The Group members conclude that currently available data are insufficient to make firm recommendations regarding screening practices for this group, and call for strategies to hasten the accumulation of observational data in addition to more rigorous trials. One can only hope that future work groups that meet to develop ACS Guidelines on Breast Cancer Screening will be able to leave issues of assessment of screening mammography and physical examination, and instead focus on more novel early detection strategies, whether molecular, imaging, or combined or at least to focus more on the more troublesome issues currently unresolved. In the meantime, the new ACS Guidelines for Breast Cancer Screening provide a wonderful summary of the state of the field in 2003, and conclude that the benefit of screening is convincing. Its presence makes it clear that it's time to move on.