Early Detection of Taxane-induced Neuropathy in Women with Breast Cancer

点击翻译按钮获取中文摘要

 DESCRIPTION (provided by applicant): The proposed training plan will provide the applicant with the foundation of knowledge, training, and skills needed to begin his interdisciplinary, translational program of research. This research focuses on the development of tools for measuring chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer survivors (BCS) who have received the chemotherapy drug paclitaxel (Taxol(r), Abraxane(r)). Although paclitaxel is highly effective as a treatment for both metastatic and non-metastatic breast cancer, exposure to paclitaxel leads to CIPN in 50-80% of BCS who receive the drug. The impact of CIPN on BCS can be severe; symptoms can interfere with occupational function and quality of life, and in some cases, force providers to stop potentially life-saving chemotherapy. Because of significant risk that CIPN symptoms pose to BCS' ability to complete treatment, function, and maintain quality of life, it is critical to identify CIPN as early as possible and monitor its progression carefully during treatment. Identifying CIPN as early as possible can alert providers to BCS at risk for severe symptoms, allowing providers to initiate teaching to minimize safety risks (e.g., falls, accidents) and initiate treatment with available agents (e.g., duloxetine, gabapentin). As treatment progresses, accurate monitoring of CIPN can help providers determine if chemotherapy needs to be delayed or discontinued and provide the team with information needed to help women plan for survivorship. Unfortunately, while early detection and accurate monitoring are important to managing CIPN effectively, current approaches to measuring CIPN are poorly suited to meet these needs. Common strategies for assessing CIPN like neuropathy grading scales or self-report questionnaires can be effective for measuring the severity and type of CIPN symptoms once they've started, but cannot detect the early signs of CIPN needed to predict symptoms and are vulnerable to patient underreporting. These approaches also lack the ability to target damage to specific types of nerves. This is especially important in the case of c-fibers, which are involved in pain signaling and increasingly have been shown to play a role in the development and perpetuation of CIPN. Recent studies have identified an accurate, sensitive approach for measuring c-fiber neuropathy that holds promise for detecting and monitoring CIPN in BCS. The approach involves measuring the increase in blood flow to the skin after stimulating temperature-sensitive nerves (c-fibers) with a heat probe (which is known as an axon reflex). Axon reflexes can be stimulated in as short a time as 20 minutes using simple heat probes, opening the door to a clinically feasible method for detecting and monitoring CIPN. The purpose of this study is to determine if axon reflexes can be used to accurately measure c-fiber damage (CIPN) in BCS receiving weekly paclitaxel.