ABSTRACT
Whether upper-limb swelling is associated with axillary web syndrome (AWS) is unknown. We recruited unilateral breast cancer (BC) patients who were scheduled for surgical intervention and lymph node dissection. The pre-operative assessment and post-operative assessment 3-4 weeks after surgery evaluated the upper-limb circumferential measurements, segmental limb volume, pain scores, grasp, shoulder range of motion (ROM), shoulder muscle power and quality-of-life scores. In the control group, the peri-elbow volume and upper-arm volume were significantly higher post-operatively than pre-operatively. In the AWS group, no significant difference was found. In comparison with the control group, the AWS group had significantly more pain, less active ROM in shoulder abduction and a lower upper-limb volume at 0-10 cm proximal to the lateral epicondyle. The incidence of lymphedema was 9.9% and was not associated with AWS. AWS is a common morbidity of lymph node dissection and causes significant pain and restricted shoulder abduction in the affected limb in BC survivors. This study is the first to investigate post-operative upper-limb volumetric changes in BC survivors with and without AWS. Our findings are of great value for the clinical effect of AWS in BC survivors, for patient education, and for developing diagnostic tools for detecting AWS.
Subject(s)
Breast Neoplasms/surgery , Lymph Node Excision , Lymphedema/epidemiology , Postoperative Complications/epidemiology , Quality of Life , Range of Motion, Articular/physiology , Upper Extremity/pathology , Adult , Anthropometry , Axilla , Female , Hand Strength , Humans , Incidence , Middle Aged , Muscle Strength/physiology , Organ Size , Pain , Shoulder , Shoulder Joint/physiopathology , Syndrome , Upper Extremity/physiopathologyABSTRACT
Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5ß1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5ß1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.
