“Given the potential delay in diagnosis related to the mammogram effects, the breast cancer safety of even short-term combined hormone use is a clinical problem.”

I believe the paper is highly cited because it addressed a controversial issue, namely breast cancer risk associated with commonly used menopausal hormone therapy, and it reports unexpected findings of more advanced-stage breast cancers and more abnormal mammograms with combined estrogen and progestin use.

The report that relatively short-term estrogen plus progestin use increases breast cancers diagnosed at more advanced stage and increases the frequency of abnormal mammograms has implications for both clinical practice and breast cancer research. Given the potential delay in diagnoses related to the mammogram effects, the breast cancer safety of even short-term combined hormone use is a clinical problem. The increased frequency of mammograms represents a newly identified risk of combined hormone use. The preponderance of observational studies suggested a longer duration of hormone exposure was needed to influence breast cancer and predicted more favorable histology and stage. The contrasting results seen in the randomized trial also raise concerns regarding the reliability of observational studies to address such breast cancer issues.

The report represents a more detailed look at one aspect of the Women’s Health Initiative randomized trial evaluating combined estrogen plus progestin compared to placebo for potential chronic disease risk reduction in otherwise healthy postmenopausal women. There was no overall chronic disease reduction seen with hormone use, and the increased breast cancers identified at higher stage was part of the reason.