Impact of Proton Irradiation Depending on Breast Cancer Subtype in Patient-Derived Cell Lines

Simple Summary Patient-specific factors must be thoroughly analyzed to minimize the side effects of applied treatments. This study examined the radiobiological response of established and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts to proton irradiation (IRR). Using clonogenic assay, gamma H2AX, and p53 staining, it was found that breast cancer cell lines of different subtypes had similar responses. However, cancer-associated fibroblasts from TNBC tumors were more resistant than those from luminal A tumors. Skin fibroblasts responded uniformly across all doses. The responses of patient-derived cell lines suggested that each patient may have a distinct radiotherapy result due to specific tumor microenvironmental characteristics.Abstract Research on different types of ionizing radiation's effects has been ongoing for years, revealing its efficacy in damaging cancer cells. Solid tumors comprise diverse cell types, each being able to respond differently to radiation. This study evaluated the radiobiological response of established (MDA-MB-231 (Triple negative breast cancer, TNBC), MCF-7 (Luminal A)) and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts following proton IRR. All cell line types were irradiated with the proton dose of 2, 4, and 6 Gy. The radiobiological response was assessed using clonogenic assay, gamma H2AX, and p53 staining. It was noticeable that breast cancer lines of different molecular subtypes displayed no significant variations in their response to proton IRR. In terms of cancer-associated fibroblasts extracted from the tumor tissue, the line derived from a TNBC subtype tumor demonstrated higher resistance to ionizing radiation compared to lines isolated from luminal A tumors. Fibroblasts extracted from patients' skin responded identically to all doses of proton radiation. This study emphasizes that tumor response is not exclusively determined by the elimination of breast cancer cells, but also takes into account tumor microenvironmental variables and skin reactions.