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Date of release: 04 January, 2010

Rethinking the impact of breast and prostate cancer screening. Part 1: The evidence


A paper recently published by Esserman and colleagues addresses the question of screening for breast cancer and prostate cancer [1]. In this paper, the authors remind us that ‘Breast cancer and prostate cancer account for 26% of all cancers in the United States, with an estimated 386,560 patients diagnosed annually: 194,280 with breast cancer and 192,280 with prostate cancer. For both cancers, there are remarkable differences between the outcomes of localized vs. advanced disease (breast cancer: 5-year relative survival rates of 98.1% vs. 27.1%; prostate cancer: 100% vs. 31.7%).’ Thus, screening has been proposed in order to decrease the mortality from both cancers, with the hypothesis that it will allow an earlier diagnosis at less aggressive stages. 


 


The authors point out that, in the USA, about 75% of men at risk have undergone screening for both cancers and about 70% of women older than 40 years report having a recent mammogram. Screening over a period of 20 years has resulted in a significant increase in cancer incidence and in detection of early cancers. PSA (prostate-specific antigen) testing has nearly doubled the chance of a man being diagnosed with prostate cancer in his lifetime. A woman’s lifetime risk of breast cancer was 1 in 12 in 1980; it is now 1 in 8.


 


The aim of the paper was to discuss whether screening is associated over the past 20 years with an increase in the rate of early disease and a decrease in regional disease. The authors analyzed the SEER data with three hypothetical scenarios of changes over time in stage-specific incidence rates. The authors confirm that the incidence of invasive breast cancer (excluding in situ lesions) has increased substantially and remains higher than the pre-screening rates. They stated that, although the incidence of high-grade cancer has dropped as a proportion of all cancers detected, the absolute numbers have not decreased as much as hoped, suggesting that early detection of tumors by screening mammography programs has not led to a more significant reduction in deaths as anticipated.


 


A comparison of the incidence rates of prostate cancer in the USA (where PSA is used widely) and in the UK (where only a fraction of the population is screened), along with dramatic increases in incidence, did not result in significant differences in mortality [2, 3]. The two prostate cancer screening trials have mixed results: the European trial showed a 20% relative decrease in mortality [2] and the USA trial found no effect on mortality [3]. For breast cancer, the relative reduction in mortality from screening in seven randomized trials ranged from 20% to 30%. Meta-analyses from the Cochrane Library [4] estimate that the reduction ranges from 0 to 20%. The observed decrease in mortality is attributable to both screening and adjuvant therapy, with estimated decreases by 7% to 23%, and by 12% to 21%, respectively. The authors suggest that, if screening has not led to a more significant reduction in deaths, it is because it increases the detection of indolent cancers and because the most aggressive cancers are missed (interval cancers). ‘In other words, tumor biology dictates and trumps stage, so the basic assumption of these screening programs that finding and treating early-stage disease will prevent late-stage or metastatic disease may not always be correct.’ There is an increased risk that the population will be over-treated. Screening is very efficient for diseases were the intermediate (precancerous) states can be detected and cured, such as cervical and colon cancers. This does not seem to be the case for breast and prostate cancers and can explain why mortality is not decreased to a greater extent by extensive screening. This is probably more true for prostate cancer than for breast cancer. However, Esserman’s paper [1] provides a table in which the numbers of mammograms and biopsies necessary to alleviate one death from breast cancer are calculated for the USA/Europe: 838 women screened for 6 years generated 5866/3352 screenings, 90/41 biopsies, and 18/15 invasive and 6/5 DCIS cancers treated ‘as if they were life-threatening when they are not’.


The authors then suggest that other strategies could help to decrease mortality: molecular profiling for the aggressivity of the tumor; early detection and prevention; developing clinical and patient tools to support informed decisions and offering treatments tailored to tumor biology; and identifying the patients at highest risk and targeting preventive interventions.

Comment

Note: In keeping with the importance of this topic, Professor Gompel's commentary on this paper is longer than usual and so will be issued next Monday, January 11.

Comentario

Anne Gompel
Unité de Gynécologie-Endocrinienne, APHP, Hôtel-Dieu Hospital and University Paris Descartes, France

    References

  1. Esserman L, Shie Y, Thompson I. Rethinking screening for breast cancer and prostate cancer. JAMA 2009;302:168592. Published October 21, 2009.
    http://www.ncbi.nlm.nih.gov/pubmed/19843904

  2. Schröder FH, Hugosson J, Roobol MJ, et al.; ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320-8.
    http://www.ncbi.nlm.nih.gov/pubmed/19297566

  3. Andriole GL, Crawford ED, Grubb RL 3rd, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310-19.
    http://www.ncbi.nlm.nih.gov/pubmed/19297565

  4. Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography [update of Cochrane Database Syst Rev 2001;(4):CD001877]. Cochrane Database Syst Rev 2006;(4):CD001877.
    http://www.ncbi.nlm.nih.gov/pubmed/17054145