mRNA Therapy to Restore Lymphatic Flow in Secondary Lymphedema

Inclusion criteria

• Women who developed upper limb lymphedema after surgery for breast cancer hormone receptor positive (HR+) more than 5 years,
• Age> 18 years,
• Body mass Index (BMI)<40,
• Stage 2 Lymphedema, moderate (defined by an increase in volume between 20 and 40% compare to the healthy limb),
• Lymphedema evolving during at least 6 months,
• Patient who adhere to optimized decongestive therapy, including a compression sleeve worn daily, integrated into an educational care pathway for the management of their lymphedema,
• Patients information and signed written consent form,
• Patients affiliated to a social security system.

Exclusion criteria

• HER2+ breast cancer triple positive,
• Other aggressive breast cancers (including triple negative and inflammatory breast cancer),
• Active cancer needing chemo- or radio-therapy,
• Metastatic breast cancer,
• Bilateral breast cancer,
• Upper limb peripheral arterial disease ipsilateral to the lymphedema,
• History of recent (< 3 months) upper limb deep venous thrombosis ipsilateral to the lymphedema,
• Previous shoulder or orthopedic surgery on lymphedematous arm
• Any abnormality of the opposite arm (arm without lymphedema),
• Trophic disorders on the lymphedematous arm,
• Last episode of cellulitis less than six months,
• Recurrent cellulitis,
• Patient participating in a clinical trial or having participated in a clinical trial within the previous 3 months or within 5 half-lives of any investigational product Immunosuppressive and anti-inflammatory treatments (topical and anti-inflammatory dermocorticoids and oral corticosteroids) in the 10 days before the injection or within 5 half-lives.
• Patient under judicial protection or enable to express consent,
• Females who are or plan to be pregnant or breastfeeding during the course of this study,
• Women of childbearing potential (WOCBP) who are sexually active and unwilling to use an adequate birth control method (hormonal or physical barrier),
• History of cancer other than breast cancer (excepted basalcell carcinoma),
• Any acute, chronic, or severe psychiatric condition that may interfere with participation in the study
• Unstable, clinically significant neurologic, psychiatric, cardiovascular (eg, pulmonary arterial hypertension, cardiac valvulopathy, orthostatic hypotension/tachycardia), pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results.
• Known allergy to bovine proteins
• Vulnerable patients (persons deprived of their liberty by judicial or administrative decision, persons undergoing psychiatric treatment, persons admitted to a health or social establishment for purposes other than research) according to article L1121-6 of the Public Health Code.