Study of Lymphatic Dysfunction in Primary and Secondary Lymphedema

Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities and accumulation of undrained interstitial fluid/lymph that results in fibrosis and adipose tissue deposition in the affected area. It can be an inherited condition (primary lymphedema) or occurs after cancer surgery and lymph node removal (secondary lymphedema). It causes a significant morbidity and is a common disabling disease affecting more than 200 million people worldwide, however there is no curative treatment for primary or secondary lymphedema.

Primary lymphedema is an inherited condition whereas secondary lymphedema develops after cancer treatments. Despite common phenotype, a molecular and histological comparison of these two pathologies has never been performed. Primary lymphedema is associated with heterozygous inactivating mutations of the gene encoding vascular endothelial growth factor C and D receptor (VEGFR-3). Primary lymphedema is rare, affecting 1 in 100,000 individuals. Secondary lymphedema is the most common cause of the disease and affects more than 200 million people worldwide.

Secondary lymphedema occurs months, sometimes years after cancer surgery suggesting that lymphedema is not only a side effect of the surgery, but involves modifications of the lymphatic architecture as well as its microenvironment, in particular adipose tissue that accumulates in the limb.

There is no cure for lymphedema because of the lack of identified therapeutic strategies able to restore collecting lymphatic draining function in the arm or in the leg. The goal will be to establish if these pathologies which possess a common denomination exhibit a similar gene expression.

Eligibility Criteria:
Inclusion Criteria:

1. Patients in who developed primary lymphedema or secondary lymphedema after breast cancer treatment.
2. Male and female over the age of 18 and under 75.
3. Patient affiliated to a social security scheme in France.
4. Patient having signed informed consent prior to inclusion in the study and prior to any specific procedure for the study.
5. Patients with no recidive \> 3 years after cancer surgery.
6. Patients with Body Mass Index \<35.
7. Patient enrolled in a care pathway for the management of their lymphedema (medical and educational care).
8. Patients wearing a compression orthosis on the limb with lymphedema.

Exclusion Criteria:

1. Patients with strong suspicion or with active bacterial or fungal infection.
2. Patient with venous insufficiency associated with lymphedema.
3. Patient with a history of deep venous thrombosis on the limb with lymphedema.
4. History of chronic inflammatory disease.
5. Active neoplasia during parallel management.
6. Patient already included in another therapeutic trial.
7. Pregnant or breastfeeding woman.
8. Metastatic cancer.
9. Bilateral breast cancer.
10. Obliterative arterial disease.
11. Multiple erysipelas.
12. Active smoking (delayed healing).
13. Medicines that may promote delayed healing (Corticosteroid therapy, immunosuppressants).
14. Medication that thins the blood (aspirin and antiplatelet agent, anti-coagulant).
15. Betadine allergy.
16. Patient under guardianship or trusteeship, persons placed under the protection of justice