Serum Insulin-Like Growth Factor-I Levels and Prostate Cancer Risk--Interpreting the Evidence

with such a history that the luteal false-negative phenomenon was observed in the Canadian study. Are menstruating women who have never used oral contraceptives at an advantage for mammographic imaging? And if so, why? Furthermore, we still have no measure of within-woman cyclic changes. All that is needed is an observational study in which premenopausal volunteers would agree to have split mammographic screening in the same menstrual cycle: one breast imaged in the follicular phase and the other in the luteal phase, with the technique kept as constant as possible. But an even more important question has been waiting to be answered ever since Tabar et al. (6) published their first results from the Two-County Study in Sweden back in 1985 that showed excess breast cancer mortality in screened women aged 40‐49 years. This mortality paradox is clearly displayed in a recent updated overview of the Swedish randomized trials (7) and parallels similar observations in the 7-year results from the Canadian National Breast Screening Study (8). However, as the end of the 1990s approaches, we know that the mortality paradox extinguishes itself 7 or more years after screening is initiated. So now the question is not so much: Why was the paradox ever observed? It is rather: Why is the benefit from screening this age group so small relative to screening older women, and why is the benefit so delayed? Even today, after many years of follow-up, two of the Swedish studies (7), Ostergotland (part of the Two-County Study) and Stockholm, show equal breast cancer mortality in screened and unscreened groups aged 40‐49 years. Can we agree that the arbitrary cutoff, age 40‐49 years versus 50‐59 years, used in the analysis of screening trials is a crude proxy for a cutoff that separates mainly premenopausal women