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Hormone replacement therapy containing progestins and given continuously increases breast carcinoma risk in Sweden

I read with interest the article by Olsson et al. reporting their experience with a large Swedish cohort in which hormone replacement therapy and the risk of breast carcinoma were studied. The title of their article and discussion section suggested that continuous rather than sequential progestin therapy increases the risk of developing breast carcinoma. Theirs was an observational cohort study not specifically designed to compare sequential versus continuous therapy, and no direct comparisons of the two hazard ratios using accepted statistical tests were performed. Their results are subject to potential selection bias among participants; only approximately 2% of the total participants were being treated with each of the sequential versus continuous combined regimens (see Table 1 in their article). This leaves a good deal of room for small differences in selection to lead to large differences in results. Furthermore, if one considers the results for women with natural menopause (generally considered the “best” determination of menopause for such studies), the hazard ratios were 2.27 (95% confidence interval [CI], 1.26 – 4.10) for the sequential regimen and 2.33 (95% CI, 1.38 –3.93) for the continuous regimen, which essentially are identical. Considering the recent conflicting data reported by multiple investigators concerning this topic, Olsson et al. might have left the issue open for discussion rather than taking a stand saying one form of therapy conferred a higher risk than the other.