Biological Effectiveness of Carbon-Ion Radiation on Various Human Breast Cancer Cell Lines

Abstract

Introduction: Carbon-ion radiotherapy (C-ion RT) is known as a highly effective local treatment and its relative biological effectiveness (RBE) has been evaluated for various types of malignant tumors. There are only a few studies on C-ion radio sensitivity in breast cancer, and there has been no evaluation by subtypes. To estimate the impact of C-ion RT for breast cancer, RBE of C-ion beams of various types of human breast cancer cell lines was evaluated by comparison with X-rays. Methods: Six human breast cancer cell lines with different subtypes, Luminal-human epidermal growth factor receptor 2 (HER2)-negative (MCF-7), Luminal-HER2-positive (BT-474), Her2-enriched (SK-BR-3), Basal-like (MDAMB- 468, HCC1937) and ductal carcinoma in situ (MCF10DCIS.com) were used. Radio sensitivities were assessed with survival curves created from colony-forming assay (CFA) and high-density surviving assay (HDS). An X-ray generator was used with 200 kV, 20 mA. The Heavy Ion Medical Accelerator in Chiba (HIMAC) was used for C-ion irradiation, with 290 MeV/u, mono-peak, linear energy transfer (LET) of 80 KeV/μm. Results: CFA was not suitable for BT474, SK-BR-3, MDA-MB-468, and HCC1937 because of their low plating efficiency. The differences between the D10 values on HDS were large with X-ray, and the survival curve shoulders for MCF7, MDA-MB-468, and MCF10DCIS.com were wide. On the other hand, the differences between the D10 values were small with C-ion beams, and the survival curves were linear without shoulders for all cell lines except a small shoulder with MCF10DCIS.com. The RBE value of C-ion beams was 2.3 to 3.6, median 2.9 in all cell lines by CFA and HDS. Conclusion: RBE around 3 by C-ion beams was seen in many types of ductal cancer. The small survival curve shoulder on MCF10DCIS.com suggested that non invasive ductal carcinoma is relatively more resistant than invasive cancer.