The aim of this study was to evaluate the clinical impact of relative biological effectiveness (RBE) variations in proton beam scanning treatment (PBS) for left-sided breast cancer versus the assumption of a fixed RBE of 1.1, particularly in the context of comparisons with photon-based three-dimensional conformal radiotherapy (3DCRT) and volumetric modulated arc therapy (VMAT). Ten patients receiving radiation treatment to the whole breast/chest wall and regional lymph nodes were selected for each modality. For PBS, the dose distributions were re-calculated with both a fixed RBE and a variable RBE using an empirical RBE model. Dosimetric indices based on dose-volume histogram analysis were calculated for the entire heart wall, left anterior descending artery (LAD) and left lung. Furthermore, normal tissue toxicity probabilities for different endpoints were evaluated. The results show that applying a variable RBE significantly increases the RBE-weighted dose and consequently the calculated dosimetric indices increases for all organs compared to a fixed RBE. The mean dose to the heart and the maximum dose to the LAD and the left lung are significantly lower for PBS assuming a fixed RBE compared to 3DCRT. However, no statistically significant difference is seen when a variable RBE is applied. For a fixed RBE, lung toxicities are significantly lower compared to 3DCRT but when applying a variable RBE, no statistically significant differences are noted. A disadvantage is seen for VMAT over both PBS and 3DCRT. One-to-one plan comparison on 8 patients between PBS and 3DCRT shows similar results. We conclude that dosimetric analysis for all organs and toxicity estimation for the left lung might be underestimated when applying a fixed RBE for protons. Potential RBE variations should therefore be considered as uncertainty bands in outcome analysis.