Interpreting Breast Cancer Survival Data by the Hazard Function: Remarkable Findings from Event Dynamics

Abstract

The report addresses the role of the hazard function in the analysis of disease-free survival data in breast cancer. An investigation on local recurrences after mastectomy provided evidence that uninterrupted growth is inconsistent with clinical findings and that tumor dormancy could be assumed as working hypothesis to understand the clinical course of the disease. Additionally, it was deemed that the lag-time between primary tumor removal and tumor recurrence is dynamically dependent on the subclinical metastasis development within the host-tumor system and, therefore, may be informative about the biology of the disease. Accordingly, the hazard function, which estimates the event risk pattern through the time, was adopted to analyze survival data. The multipeak pattern of the hazard function suggested that the process metastasis development has discontinuous features. A new paradigm of breast cancer metastatic development was proposed, involving the notions of tumor homeostasis, tumor quiescence in specific metastatic microscopic phases and surgery-related acceleration of the metastatic process. All analyses by prognostic factors (e.g., by menopausal status) or treatment modalities (e.g., by adjuvant chemotherapy) or other parameters (e.g., site of metastasis), provided coherent data in agreement with the model. The hazard rate function allowed addressing several clinical questions including meaning of ipsilateral breast tumor recurrence (IBTR), oncologic effect of delayed breast reconstruction, surgery related metastasis acceleration, possible role of anti-inflammatory drugs and body mass index (BMI) to modulate the recurrence risk. We conclude that the hazard function is a powerful tool to investigate the post-surgical course of early breast cancer and other operable tumors and to make inferences on their biology.