© 2005 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Reason for Late-Stage Breast Cancer: Absence of Screening or Detection, or Breakdown in Follow-Up?
Affiliations of authors: National Cancer Institute, Division of Cancer Control and Population Sciences, Applied Research Program, Bethesda, MD (ST); Henry Ford Health System, Detroit, MI (MU-Y); Kaiser Permanente Southern California, Pasadena, CA (AG); Group Health Cooperative, Seattle, WA (LI); Kaiser Permanente Colorado, Denver, CO (KB); Group Health Cooperative, Seattle, WA (WB)
Correspondence to: Stephen Taplin, MD, MPH, National Cancer Institute, Division of Cancer Control and Population Sciences, Applied Research Program, 6130 Executive Blvd., MSC 7344, EPN - 4005, Rockville, MD 20852 (e-mail: taplins{at}mail.nih.gov).
We thank Dr. Whittemore for her observations and hope that our explanation below reduces confusion about our work.
Dr. Whittemore states that our findings require a leap of faith from "screening leads to smaller cancers" to "screening reduces mortality" and cites evidence from the Canadian National Breast Screening Study, a randomized trial in women aged 40–49 years, that mammography does not reduce mortality. She notes that, in the Canadian trial, the proportion of large tumors decreased among women who received screening but that mortality did not. However, the proportion of large tumors can be deceiving because the proportion of all cancers detected is influenced by the propensity of screening to find early cancer, which inflates the denominator of that proportion (i.e., all invasive cancers) (1). Instead, we believe that the population-based incidence of large tumors is a better indicator of screening's impact, and in studies that have shown a reduction in mortality associated with screening the incidence of large tumors decreased before mortality decreased (2,3). Dr. Whittemore also notes the important fact that our study did not include women aged 40–49 years and that our study did not evaluate the efficacy of screening. Therefore, the results of the Canadian trial are not directly relevant to our results.
We restricted our evaluation to women aged 50 years or older because the strongest evidence for a screening benefit is in this age group, as recently affirmed by the U.S. Preventive Services Task Force and others (4,5). Our definition of late-stage disease included large tumors and the presence of metastases because the incidence of large tumors declines with screening implementation (6) and because a reduction in late-stage disease is an indicator of screening success in a population (3,7). With our definition of late-stage disease as the indicator, we showed that the largest proportion of late-stage cancers occurred among unscreened women. We therefore concluded that the best chance for further mortality reduction was to reach the unscreened women. Although we did not make it clear in our article, "reaching the unscreened" simply means making sure that women without screening have access to mammography, understand what the test has to offer, and are making an informed choice about their care.
Dr. Whittemore describes a valid concern that our definition of late-stage disease, which includes large tumors, could influence our conclusions. Among women with late-stage disease, the proportion of women with tumors at least 3 cm in greatest diameter (n = 1112) and of those with metastases (n = 235) differed among the "absence of screening," "absence of detection," and "potential breakdown in follow-up" groups (3 cm, no metastases: 49%, 43%, and 8%, respectively; metastases: 67%, 25% and 8%, respectively). However, this difference reinforces the priorities for improvements in screening implementation reported in our paper because the proportion without screening is even higher among metastatic cases.
Dr. Whittemore suggests that mortality would have been a better endpoint. A nested case–control study of screening efficacy in which breast cancer deaths are used as the endpoint has been undertaken within the Cancer Research Network, but the results have not yet been published. We did not evaluate the efficacy of mammography, which is best done in a randomized trial, but assumed that mammography is efficacious and demonstrated that there are opportunities to improve the screening process. We agree that the mortality impact of improvements in the screening process will need evaluation, but we do not think that women and health plans need to wait for that evaluation before pursuing those improvements.
REFERENCES
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(6) Taplin SH, Mandelson MT, Anderman C, White E, Thompson RS, Timlin D, et al. Mammography diffusion and trends in late-stage breast cancer: evaluating outcomes in a population. Cancer Epidemiol Biomarkers Prev 1997;6:625–31.[Abstract]
(7) Prorok PC. Evaluation of screening programs for the early detection of cancer. In: Cornell RG, editor. Statistical methods for cancer studies. New York (NY): Marcel Dekker, 1984. p. 267–328.
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J Natl Cancer Inst 2005 97: 400.
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