Photodynamic therapy as a strategic ally in radiotherapy for triple-negative breast cancer: the importance of treatment order.

Purpose: Triple-negative breast cancer (TNBC) accounts for 20% of all breast cancer cases and is notably resistant to radiotherapy (RT). Photodynamic therapy (PDT) using porphyrins or their derivatives has shown promise as a potential cancer treatment and immune activator. This study evaluated the effects of combining PDT and RT in sublethal conditions for TNBC using in vitro and in vivo models.

Methods: In vitro, PDT was combined with RT (2.5 Gy) using a porphyrin (TMPyP, 32 μmolL^-1) and red light (660 ± 15 nm) with a dose of 50 Jcm^-2. We assessed cell viability, survival, apoptosis, ROS, singlet oxygen, and GSH/GSSG ratio. In vivo, we used a TNBC-bearing mouse model and combined PDT with RT in four sessions, comparing treatment sequences. We evaluated tumor volume, clinical manifestations, survival, metastasis in the lungs, ROS, singlet oxygen, and glutathione levels.

Results: Cells treated with PDT + RT had a lower survival fraction, although PDT alone showed higher apoptosis and singlet oxygen levels than RT-treated groups. In vivo, the treatment sequence plays a crucial role: PDT after RT resulted in better clinical outcomes, prolonged survival, and fewer lung nodules compared to RT, with higher singlet oxygen levels likely stimulating an immune response.

Conclusion: Our results show that PDT can be a valuable adjunct in the RT of TNBC, with the treatment sequence playing a crucial role in enhancing efficacy.