Short summary

Breast cancer-related lymphedema (BCRL) is a severe and life-long side-effect to breast cancer treatment. BCRL increases the risk of infections and decreases health-related quality of life in patients. Studies have shown that CD4+ immune cells play a critical role in the development of BCRL. Tacrolimus is a immunosuppressive and anti-inflammatory drug which targets the CD4+-cells. Tacrolimus treatment of BCRL has shown promising results in animal studies.

Rationale

Breast cancer (BC) is the second most common cancer in women with an incidence of 4,694 in the years 2012-2016 in Denmark. Treatment of BC can include axillary lymph node dissection (ALND), chemotherapy and radiotherapy which are all risk factors for the development of breast cancer related lymphedema (BCRL). BCRL is a severe and life-long side-effect to BC treatment. BCRL is a localized tissue swelling caused by accumulation excess lymphatic fluid in the skin and subcutaneous tissue, because the lymph vessels which are responsible for draining the arm are compromised. BCRL is a progressive condition, and in the early stage a reversible condition due to accumulation of liquid. However, the condition will become irreversible with fat deposition and formation of fibrosis if untreated. BCRL increases the risk of infections and decreases health-related quality of life (HR-QOL) in the patients. Studies have shown that in addition to the objective measures concerning BCRL (e.g. arm-volume, diminished strength and bioimpedance measures), BCRL can cause a decrease in self-confidence due to a distorted body image and increases self-consciousness and negative emotions. The patients all suffer from psychical, psychological and emotional consequences from BCRL. There is often a discordance between patients' self-perceived signs and symptoms of BCRL and the clinical objective manifestations. Self-reported symptoms are predictive factors for BCRL and are also associated with decreased health related HR-QOL even in the absence of objective symptoms. Assessment of patients HR-QOL measures are made by using Patient reported outcome measures (PROM). PROMs are an increasingly popular tool to understand and optimize treatment based on the patient's subjective measures. It is therefore key in understanding and setting goals for the treatment of BCRL.

No prophylactic or curative treatment is currently available which is why patients are treated for their symptoms with manual lymphatic drainage, physiotherapeutic exercises and life-long compression therapy amongst other things.

Studies have shown that CD4+-cells plays a critical role in developing lymphedema. The cells facilitate inflammation and fibrosis formation in the subcutaneous tissue which inhibits lymphatic regeneration. CD4+-cells are therefore a potentially pharmacological target in the treatment of BCRL.

Tacrolimus is an immunosuppressive and anti-inflammatory macrolide. Tacrolimus is already used to treat diseases like atopic dermatitis and has an established safety profile. Tacrolimus is administrated locally on the skin to inhibit CD4+-cells. Tacrolimus as treatment of lymphedema has shown promising results in animal studies with an absence of adverse eventsside-effects. Ointment containing Tacrolimus is currently branded under the name Protopic. Protopic can easily and quickly be applied to the skin. Tacrolimus has the potential to cure an otherwise uncurable and life-long side-effect of BC and will therefore benefit a large number of patients who suffers from BCRL.

In this study we seek to investigate the effect of Tacrolimus on BCRL and how the treatment affects the HR-QOL in the patients. We have all prerequisites and requirements to conduct this study. Both objective and subjective measures (PROM) are taken into account when evaluating the effect of the treatment.

Objectives

To assess the effect of Tacrolimus treatment on lymphedema according to objective measures and how it influences HR-QOL in patients with BCRL.

Description of the cohort

The population of the study consists of women from the Region of Southern Denmark who has been diagnosed with lymphedema as a result of their breast cancer treatment.

Data and biological material

• Medical anamnesis including concomitant drug-use

• Breast cancer treatment

• Age

Collaborating researchers and departments

Department of Plastic Surgery, Odense University Hospital

• MD, PhD Student Mads Gustaf Jørgensen
• Medical Student Frederik C. Gulmark Hansen