Chemotherapy targeting regional lymphatic tissues to treat rabbits bearing VX2 tumor in the mammary glands

Abstract

Lymph node status is one of the decisive prognostic factors in breast cancer. Chemotherapy targeting regional lymphatic tissues has emerged as a promising approach for the treatment of malignancies with high tendency to disseminate lymphatically. In this study, rabbits bearing well-developed VX2 tumors in the mammary gland received carboplatin-activated carbon suspension (CP-CH) administered subcutaneously (s.c.), carboplatin solution (CP-Sol) s.c., CP-Sol intravenously (i.v.), or a sham therapy, respectively, 6 weeks after tumor implantation. The platinum concentrations in breast tumors, axillary lymph nodes, and distant metastases were determined by Zeeman atomic absorption spectrometry (AAS). Therapeutic effects were assessed in terms of tumor and node volume ratio, cell proliferation and necrosis. Compared to CP-CH or CP-Sol s.c., CP-Sol i.v. exhibited more strong cytotoxic efficacy on breast tumor and distant metastases. In contrast, CP-CH s.c. produced much higher drug concentrations and more evident antitumor activities in axillary nodes, as demonstrated by the inhibited node growth, declined mRNA level of proliferating cell nuclear antigen (PCNA), and more extensive tumor necrosis. Based on these data, we recommend lymphatic chemotherapy to be used as an effective component of the approach to the systemic treatment on breast cancer patients with positive lymph nodes.