Insights From Mixture Cure Modeling of Molecular Markers for Prognosis in Breast Cancer

Abstract

With the ultimate aim of improving clinical management of breast cancer, investigators have sought to identify molecular genetic markers that stratify newly diagnosed patients into subtypes differing in short- or long-term prognosis. Conventional survival models can fail to describe adequately the relationship between subtype and disease recurrence, particularly when there is a substantial proportion of long-term disease-free survivors. The observed patterns of disease-free survival in an undifferentiated patient cohort may be explained by an underlying mixture of two subgroups: patients who will remain free of disease in the long term (ie, cured), and those who will experience disease recurrence within their lifetime (ie, susceptible.) In this article, we review the concepts and methods of the mixture cure models and apply them in the analysis of molecular genetic prognostic factors for disease-free survival and time to disease recurrence in a cohort of patients with axillary lymph node–negative breast cancer.