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Delayed Benefit of Mammography Screening in Premenopausal Women

Department of Surgery, National Naval Medical Center and the Uniformed Services University, National Cancer Institute, Bethesda, MD
Division of Cancer Prevention, National Cancer Institute, Bethesda, MD

To the Editor:

Demicheli et al point out that in the mammography screening trials, an early excess in breast cancer mortality is seen among premenopausal women who undergo screening.¹ Yet a reduction in breast cancer mortality in the screened group is evident much later (after approximately 12 years).² The authors suggest that surgery may perturb the natural history of breast cancer (perhaps by releasing cytokines that could bestow autonomy on micrometastases), and that the early excess in mortality among premenopausal women who undergo mammography screening might be attributed to surgery (early detection of breast cancer results in early surgery, and this in turn produces an early excess in mortality).

However, the authors fail to provide an explanation for the apparent long-term benefit of mammography screening in premenopausal women. We suggest that surgical perturbation of the natural history of breast cancer might explain this observation. At the conclusion of the mammography screening trials, women in the control (unscreened) groups were often invited to undergo screening.³ As a result, an excess of cancers were diagnosed and treated surgically in the control groups following completion of the screening trials. If surgery does indeed perturb the natural history of breast cancer, then inviting the controls to undergo delayed screening may have resulted in a delayed increase in breast cancer mortality in those women. Thus long-term comparisons of breast cancer mortality trends between control and study groups may give the false impression that screening has a delayed benefit in the study groups, when, in fact, the better long-term outcome of women in the study groups might actually be due to a delayed one-time increase in breast cancer mortality in the controls.

Demicheli et al suggest that the potential effects of surgery might differ between pre- and postmenopausal women. If so, then the hormonal milieu at the time of surgery may influence early breast cancer mortality. Several retrospective studies have suggested that this is indeed the case, and that the timing of surgery in relation to the menstrual cycle may have an impact.⁴ Clearly, randomized prospective trials are needed to resolve these issues. Neoadjuvant hormonal therapy may ultimately prove effective in modulating these effects.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Demicheli R, Bonadonna G, Hrushesky WJM, et al: Menopausal status dependence of early mortality reduction due to diagnosis of smaller breast cancers (T1 v T2–T3): Relevance to screening. J Clin Oncol 22:102-107, 2004[Abstract/Free Full Text]

2. Jatoi I: Breast cancer screening. Am J Surg 177:518-524, 1999[CrossRef][Medline]

3. Sjonell G, Stahle L: Scientific foundation of mammographic screening is based on inconclusive research in Sweden. BMJ 319:55, 1999[Free Full Text]

4. Jatoi I: Timing of surgery for primary breast cancer with regard to the menstrual phase and prognosis. Breast Cancer Res Treat 52:217-225, 1998[CrossRef][Medline]

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