In a recent commentary, Shapiro and colleagues1 provided their perspective on the strength of the evidence relating the time-dependent decrease in combined menopausal hormone therapy use to a decrease in breast cancer incidence, examining three studies reporting on the trends in breast cancer incidence following declines in hormone therapy use. They concluded that “the ecological evidence is too limited to either support or refute the possibility that hormone therapy causes breast cancer”. Their conclusions were based mainly on the “lower reliability of data collected at the population level than analytic data collected at the individual level” and that “precise adjustment for the confounding effect of changes in mammography screening” was needed. In this regard, a report from the Women's Health Initiative (WHI) estrogen plus progestin (progestogen) (E+P) randomised clinical trial in the New England Journal of Medicine has directly addressed these issues2 but was not cited in the Shapiro review. In the WHI report, individual use of mammography in the years immediately prior to and after E+P use was provided and no differences in mammography utilisation were seen comparing women in the E+P group to those in the placebo group. In addition, breast cancer incidence was seen to rapidly decline after intervention ended but only in the E+P group, directly addressing the two major concerns raised.2 In addition, while the Shapiro review considered only three reports addressing the timing of E+P use and change in breast cancer incidence, a large number of more recently reported analyses addressing this issue found generally consistent associations between reduction in menopausal hormone therapy use and subsequent lower breast cancer incidence.3–10

Addressing the topic of E+P and breast cancer risk, a prior commentary by Shapiro and colleagues on the WHI randomised, placebo-controlled clinical trial evaluating E+P challenged the conclusion that combined …