Short summary

The primary aim of this study is to validate the protein neurofilament light chain (NFL) as a biomarker of the side effect paclitaxel-induced peripheral neuropathy (PIPN) and its utility in predicting this side effect in patients with breast cancer. The study will include breast cancer patients from three Danish Hospitals.

Rationale

Paclitaxel is a chemotherapeutic agent belonging to the group of taxanes. It is a very commonly used drug and is used to treat breast-, ovarian-, and lung cancer patients, among others. PIPN is a side effect in cancer patients treated with paclitaxel. It is characterized by dysesthesia, paresthesia, and neuropathic pain in hands and feet, and clinical signs of PIPN include sensory loss, tingling, and pain. PIPN affects two out of three cancer patients and thus constitutes a major clinical challenge, being a barrier to the effective use of paclitaxel and a cause of long-term disability among cancer survivors. Symptoms are mostly reversible but may persist for several years after treatment. With an increasing rate of long-term survivors (e.g., >80% of breast cancer patients, who are often treated with taxanes), occurrence of PIPN is particularly problematic. The success of chemotherapy treatment is correlated to dose, and chemotherapy-induced peripheral neuropathy (CIPN) is the major reason for dose limitation and early termination of treatment. Traditionally, it has been a challenge to investigate CIPN both in the clinic and in research. In many cases, CIPN is not discovered before the symptoms are severe and irreversible, and sometimes CIPN first occurs after the treatment has stopped, defined as Coasting. One central challenge in studying CIPN is the complexity of the condition, which includes pain, reduced and altered sense of touch, tingling and sleeping sensation in the distal extremities, decreased muscle strength, and weak or lack of deep tendon reflexes. Description of CIPN thus depends on both objective and largely on the patient's subjective perception and ability to describe the symptoms, which is difficult since the symptoms are slowly progressing and often masked by a lot of other side-effects due to the chemotherapy. NFL is an abundant structural protein highly expressed in neurons (15) and might be a useful biomarker of PIPN. Damage to axons leads to release of NFL into the interstitial fluid and eventually to the blood. Increased NFL levels likely represent axonal damage, which is characteristic of neurodegeneration and thus PIPN The primary aim of this study is to validate the protein neurofilament light chain (NFL) as a biomarker of the side effect paclitaxel-induced peripheral neuropathy (PIPN) and its utility in predicting this side effect in patients with breast cancer.

Description of the cohort

We will include a total of 188 breast cancer patients diagnosed with breast cancer who are scheduled for paclitaxel treatment. These patients will be found at Odense University Hospital, University Hospital of Southern Denmark, Vejle, and University Hospital of Southern Denmark, Sønderborg.

Data and biological material

We will include data from the patient's journal (cancer diagnosis, comorbidities, comedication, hemoglobin, kidney and liver function etc. We will also collect data with a questionnair answered by patients on their potential pain, blood samples, and skin biopsies for those who agree to this.

Collaborating researchers and departments

Department of Oncology, Vejle Hospital

• Lise Ventzel

Department of Oncology, Sønderborg Hospital

• Erik Hugger Jakobsen

Department of Oncology, Odense University Hospital

• Lise Eckhoff
• Marianne Voksen