The breast cancer “plunge” after initial publication of the WHI results: An alternative explanation

From 2002 to 2003, the breast cancer incidence in the United States, as reported by the National Cancer Institute's Surveillance Epidemiology and End Results (SEER 9) database, appeared to decrease by 6.7%. This phenomenon has been attributed to a reduction in the use of menopausal hormone therapies after the initial publication of the Women's Health Initiative (WHI) study results in July of 2002. However, attempts to draw a causal association between the use of menopausal hormone therapies and the incidence of breast cancer have not accounted for the facts that prescriptions of estrogen-plus-progestin menopausal therapies, which are associated with increased rates of breast cancer, fell by 53% from 2002 to 2003, while prescriptions of estrogen-only therapies fell by only 27%. To address this issue, we analyzed the effects of the higher rate of discontinuation of estrogen-plus-progestin menopausal therapies relative to estrogen-only treatments during the 2002–2003 time period, based upon the effects of different types of menopausal hormone therapies on breast cancer incidence as determined by the WHI interventional hormone trials. This approach demonstrates that the relative persistence with menopausal estrogen-only therapies – as compared to estrogen-plus-progestin therapies – can explain the reduction in breast cancer incidence from 2002 to 2003. In addition, we point out the incompatibility of the breast cancer incidence rates found in the two WHI interventional hormone trials and the rates reported in the SEER 9 database. Based on these findings, we conclude – as previously demonstrated in the estrogen-only arm of the WHI interventional hormone trials – that menopausal estrogen-only use is not responsible for increasing the risk of breast cancer in menopausal women and may, in fact, be protective. Additional studies are still needed to better define the relationship between different types of menopausal hormone therapies and the incidence of breast cancer.