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A tangled web: factors likely to affect the efficacy of screening mammography.

Given the direct and indirect costs of mammographic breast cancer screening in North America (1,2), any evidence leading to the improved efficacy of screening mammography should be welcome. The importance of high technical standards to achieve mammographic accuracy has been recognized (3). Improved accuracy should lead to improved efficacy, namely, further reductions in mortality from breast cancer. The efficacy of breast screening is most contested in women who are 40–49 years old (4), many of whom are premenopausal. In this group, a 16% reduction in breast cancer mortality has been observed 7–10 years after the initiation of screening (5), about half of that observed in women who are 50–69 years old. Although mammographic sensitivity is indisputably lower (less accurate) in younger women, one expert has asserted (6) that “Nothing magical happens at age 50. There is no significant difference in breast tissue as seen by mammography” when women in their 40s are compared with women in their 50s. Tabar et al. (7) attributed the smaller benefit of screening women in their 40s to shorter sojourn times in some women and to the long interval between screening examinations that occurred in the Two-County Trial. This commentary will give an overview of available information about biologic and life style factors that may reduce the accuracy of screening mammography and thereby also reduce screening efficacy. Among the factors diminishing the efficacy of screening (Table 1), false-negative mammograms are of crucial importance. Delay in the detection of breast cancer must reduce the opportunity to reduce mortality. This conviction led to a study of menstruating women that found that the chances of a woman having a false-negative mammographic examination were almost doubled in the luteal phase of the menstrual cycle compared to what the chances were in the follicular phase, although only in women who had ever used exogenous hormones (presumably oral contraceptives) (8). Possible biologic mechanisms that could explain this observation are increased mammographic density associated with breast tissue changes in the luteal phase and luteal mastalgia (pain) restricting mammographic compression. More recently, White et al. (9) reported a small but statistically significant increase in mammographic density in the luteal phase. This observation is consistent with the increase in falsenegative mammograms previously reported (8), with the conclusion that early breast cancer detection is more difficult to achieve in younger women (10) and with the generally accepted notion that increased density (variously described as mammographic, parenchymal, and fibroglandular) is associated with decreased mammographic sensitivity (Table 2). To identify other factors that may reduce screening efficacy by reducing mammographic accuracy in both premenopausal and postmenopausal women, it may be useful to consider the following issues: