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Nelson HD, Tyne K, Naik A, et al. Screening for Breast Cancer: Systematic Evidence Review Update for the US Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Nov. (Evidence Syntheses, No. 74.)

4Discussion

Summary

Table 9 summarizes the evidence for this review. Breast cancer mortality benefits from randomized controlled trials of screening are based on estimates of women who were randomly assigned to screening, whereas harms are based on data from women actually screened.

Table 9. Summary of Evidence.

Table 9

Summary of Evidence.

Trials of mammography screening for women age 39–49 years indicate a 15% reduction in breast cancer mortality for women randomly assigned to screening versus those assigned to controls. This translates to a number needed to invite for screening to prevent one breast cancer death of 1,904 (95% CrI, 929–6,378) over multiple screening rounds that varied by trial. These results are similar to those for women age 50–59 years, but indicate less effect than for women age 60–69 years. For women age 70 years or older, results from the Swedish Two-County trial68 of women age 70–74 years indicate no mortality reduction. However, these results are limited by including only a few women from one sample. Interpreting trial results stratified by age requires caution because except for the Age trial,66 age-specific results are subanalyses of trials designed for different purposes.

Although the addition of the Age trial66 did not markedly change the results of the meta-analysis, 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 recent trial that reflects current screening, diagnostic, and treatment practices better than its predecessors, particularly those from the pretamoxifen era. As such, it is the most relevant trial. However, its results, although 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.32

Harms of mammography screening have been identified, but their magnitude and effect 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 breast cancer such as BRCA mutation carriers. Patient adverse experiences, such as pain during procedures and anxiety and other psychosocial responses, are common but seem to be transient and do not discourage future screening practices. This may differ 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 types of cancer will progress, how quickly cancer will advance, and expected lifetimes.

Harms also include downstream consequences of false-positive mammography results, such as additional imaging and biopsy. Younger women have higher rates of additional imaging and lower rates of biopsy than older women. Additional imaging may be particularly useful in selecting biopsy candidates among premenopausal women who have denser breast tissue and more fibrocystic changes than postmenopausal women.

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, which restricts 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 Russian57 and Shanghai78 trials simultaneously showed no reductions in mortality and increased numbers of benign biopsy results done as a result of BSE instruction.

Limitations

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 age 70 years and older, which is a rapidly growing population in the United States. Recent observational studies indicate that regular screening mammography among older women is associated with earlier-stage disease110, 111 and lower breast cancer mortality.111 For the many older women who might live 20–30 years longer, breast cancer detection and early treatment could reduce morbidity as well as mortality, thereby 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 in this manner. As diagnostic and treatment experiences become more individualized47 and include patient preferences, it becomes even more difficult to characterize benefits and harms in a general way. Many patients would consider quality-of-life an important outcome, although it is a more difficult outcome to measure and report in trials.

New technologies, such as digital mammography and MRI, have become widely used in the United States without definitive studies of their effect on screening. Consumer expectations that new technology is better than old may obscure potential adverse effects, such as higher false-positive results 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. No definitive studies of the appropriate interval for mammography screening exist, although trial data reflect screening intervals from 12–33 months.

Future Research

Additional research on benefits and harms of mammography screening with quality-of-life outcomes, as well as morbidity and mortality outcomes, would provide further understanding of the implications of routine screening. Data for specific groups of women, based on racial and ethnic background, access to screening, or existence of co-morbidities, for example, could inform screening practice. Studies of older women are essential in order to determine appropriate screening regimens for them including when to discontinue screening. Studies on the role of MRI in screening are required in order to incorporate this technology appropriately in the screening process. More information on DCIS is needed, including its implications and outcomes.

Conclusions

Our meta-analysis of mammography screening trials indicates breast cancer mortality benefit for all age groups from 39–69 years, with insufficient data for older women. False-positive results are common in all age groups and lead to additional imaging and biopsies. Women age 40–49 years experience the highest rate of additional imaging whereas 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.

Cover of Screening for Breast Cancer
Screening for Breast Cancer: Systematic Evidence Review Update for the US Preventive Services Task Force [Internet].
Evidence Syntheses, No. 74.
Nelson HD, Tyne K, Naik A, et al.

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