Abstract
Breast-conservation surgery (BCS) is now utilized in patients with stage I and II invasive breast cancer. However, positive surgical margins are associated with recurrence, and therefore some form of localized postoperative therapy (radiation/chemotherapy) is necessary to eliminate remaining cancer cells. Existing modalities have significant treatment-limiting side effects; therefore, alternative forms of localized therapy need to be explored. We studied the ex vivo effects of photochemical internalization (PCI) using 4 chemotherapeutic agents: cisplatin, cisplatin analog [D prostanoid, DP], doxorubicin, and bleomycin) on 3 breast cancer cell lines: MCF-7, MDA-MB-435, and MDA-MB-231. Illumination was carried out using a 670-nm diode laser at 5 mW/cm2 following incubation in the photosensitizer with aluminum phthalocyanine disulfonate. Toxicity was investigated using colony-forming assays and the mechanism of cell death was determined using Annexin flow-cytometry. We found that toxicity of DP and bleomycin was significantly enhanced by PCI compared with drug alone but was unchanged for cisplatin and doxorubicin. PCI treatment caused a decrease in the percentage of viable cells, predominantly by enhancing apoptosis. The action was synergistic across all 3 cell lines tested for DP and bleomycin. Thus, with appropriate delivery devices and choice of chemotherapeutic agents, PCI holds the promise of enhancing tumor cell toxicity surrounding the cavity of BCS resection sites and thereby decreasing local recurrence.