The Role of Lymph Flow on MTLn3 induced Breast Cancer

Purpose: Secondary lymphedema is the chronic accumulation of lymph with no definitive cure. At least 22 % of axillary lymph node dissection and biopsies in breast cancer (BC) patients can lead to secondary lymphedema. There are no pharmaceuticals approved for lymphedema however manual medicine techniques have been designed to enhance lymph flow. Many clinicians fear manual medicine techniques, such as osteopathic lymphatic pump treatment (LPT), could promote metastasis in BC patients although there is a lack of literature supporting this notion. Our previous studies have shown LPT increases lymph flow and leukocyte concentrations in the lymph of rats. Physical activity increases lymph flow and has been associated with improved quality of life in BC patients and proposed as a modulator of the immune system. Therefore we proposed increasing lymph flow does not promote primary tumor growth. Methods: To determine the effect of LPT on BC, rats were randomized on day 0 into control, sham and LPT groups and injected with MTLn3. The LPT group received LPT under anesthesia, the sham group received anesthesia and the control group did not receive LPT or anesthesia. Treatment was administered once daily at days 14-24 post-injection. At days 0, 7, 14, 21 and 25, primary tumors were excised, measured, weighed and prepared for histological examination. Axillary sentinel lymph nodes (SLN) were excised, weighed and leukocyte populations were measured. Results: In the control rats, tumor weight increased significantly between days 14 (0.06 grams) and 25 (2.86 grams) post-injection. Tumor volume in situ increased significantly between days 14 (1.17 cm3) and 25 (2.75 cm3) post injection. Consistent with tumor growth, immunofluorescent staining revealed angiogenesis between days 14 and 25. Furthermore, SLN weight increased significantly (three-fold increase) and pathology confirmed metastasis by day 25. The number of T cells, B cells, NK cells, dendritic cells and macrophages were significantly higher in the SLN by day 25. LPT did not increase primary tumor size compared to control and sham groups. Interestingly, sham significantly increased SLN size (five-fold increase) when compared to control and LPT decreased SLN size when compared to sham. Conclusions: Our results suggest LPT does not increase primary tumor growth and negated the effect of sham treatment on the sentinel lymph node. Therefore, future studies will focus on how LPT reduces sham induced enlargement and determine if LPT reduces tumor load or fluid in the SLN.