summarizes the evidence for this review. Note that breast cancer mortality benefits from randomized controlled trials of screening are based on estimates of women invited to screening, whereas harms are based on data of women actually screened.
Trials of mammography screening for women age 39 to 49 indicate a statistically significant 15% reduction in breast cancer mortality for women randomized to screening versus those not. This translates to a number needed to invite for screening to prevent one breast cancer death of 1,904 (95% CrI 929 to 6,378). These results are similar to those for women age 50 to 59, but less than women age 60 to 69. For women age 70 and older, results from the Swedish Two-County trial of women age 70 to 74 indicate no mortality reduction. However, these results are limited by including only a small number of women from a single population. Interpreting trial results by age requires caution, because, except for the Age trial, age-specific results are sub-analyses of trials designed for different purposes.
Although the results of the meta-analysis have not changed markedly with the addition of the Age trial (29
), its contribution to the evidence base is important. The Age trial is the only trial of mammography that specifically evaluates the effectiveness of screening women in their 40s. It is the largest trial and draws from a community population. It is the most recently performed trial, reflecting current screening, diagnostic, and treatment practices better than its predecessors, particularly those from the pre-tamoxifen era. As such, it is the most relevant trial. However, its results, while consistent with the meta-analysis in the direction of benefit, are not statistically significant. Also, its applicability to women in the United States is not clear in light of important differences between mammography screening practices in the United States and United Kingdom (63
Harms of mammography screening have been identified, but their magnitude and impact are difficult to measure. The absolute level of radiation exposure and corresponding radiation risk from mammography is very low. Special considerations may be needed, however, for women exposed to additional radiation for other purposes, or women particularly susceptible to radiation and breast cancer such as BRCA mutation carriers. Patient adverse experiences, such as pain during procedures and anxiety and other psychological responses, are widely experienced, but appear to be transient and do not adversely influence future screening practices. This may vary for individual women. Estimates of the magnitude of overdiagnosis vary depending on the analytic approach used. These estimates are difficult to apply because, for individual women, it is not known which cancers will progress, how quickly cancers will advance, and expected lifetimes.
The effectiveness of CBE has not been proven in large, well designed trials. Current ongoing trials are limited to countries that do not provide routine mammography screening, restricting their applicability to the United States. Work ups for false positive findings subject women to additional imaging and procedures countering the potential benefits of this low-technology approach. For BSE, the Russian and Shanghai trials simultaneously showed no reductions in mortality and increased numbers of benign biopsies performed as a result of BSE instruction.
Although more information is available to determine the benefits and harms of routine breast cancer screening in average-risk women, questions remain unanswered. The least amount of data is available for women over age 70, a rapidly growing population in the United States. Recent observational studies indicate that regular screening mammography among older women is associated with earlier stage disease (64
) and lower breast cancer mortality (65
). For the many older women who might live another 20 to 30 years, breast cancer detection and early treatment could reduce morbidity as well as mortality, optimizing independence, function, quality of life, and costs of care in the final years.
Breast cancer is a continuum of entities, not just one disease, that needs to be taken into account when considering screening and treatment options and when balancing benefits and harms. None of the screening trials consider breast cancer this way. As diagnostic and treatment experiences become more individualized (66
) and include patient preferences, it becomes even more difficult to characterize benefits and harms in a general way.
New technologies, such as digital mammography and MRI, are becoming widely used in the United States without definitive studies of their impact on screening. Consumer expectations that new technology is better than old may obscure potential adverse effects such as higher false positives and expense. No screening trials incorporating newer technology have been published, and estimates of benefits and harms in this report are based predominantly on studies of film mammography. There are no definitive studies of the appropriate interval for mammography screening, although trial data reflect screening intervals from 12 to 33 months.
Our meta-analysis of mammography screening trials indicates breast cancer mortality benefit for all age groups between age 39 to 69, with insufficient data for older women. False positive results are common in all age groups and lead to additional imaging and biopsies. Women age 40 to 49 experience the highest rate of additional imaging while their biopsy rate is lower than older women. Mammography screening at any age is a tradeoff of a continuum of benefits and harms. The ages at which this tradeoff becomes acceptable to individuals and to society are not clearly resolved by available evidence.