A Principal Stratification Approach to Assess the Differences in Prognosis between Cancers Caused by Hormone Replacement Therapy and by Other Factors

Several recent studies have reported that women who have used hormone replacement therapy (HRT), and developed breast cancer, tend to have a better prognosis than women with breast cancer who have not used HRT. One possible explanation is that tumors caused by HRT are more benign than tumors caused by other factors. Although it is relevant to quantify differences in prognostic factors across subtypes of breast cancer, it is not obvious how to do this correctly. This is because the tumors which occur among women who are treated with HRT are a mixture of HRT-induced and other tumors. We propose a framework based on principal stratification to distinguish women with HRT-induced tumors from women with tumors caused by other factors. To estimate the difference in prognosis for these two groups, we propose two estimation methods, which can be used under both cohort and case-control sampling schemes.