Adjuvant hormono-radiotherapy applied to breast cancers have been published for many years as an efficient neo-adjuvant treatment. Given the common hormonal dependence of breast cancer and the potential synergistic effect of these two treatment modalities, this strategy has been increasing in the adjuvant setting. Indeed, two strategies are used in daily clinical practice: upfront aromatase inhibitors or sequentially after a variable delay of tamoxifen (TAM). These molecules may thus interact with radiotherapy (RT). Retrospectives studies did not show any differences in terms of loco-regional recurrences between concurrent or sequential radio-hormono-therapy. Lung and skin fibroses due to concurrent treatment are still under debate. Nevertheless, late side-effects appeared to be increased particularly in hypersensitive patients identified by the lymphocyte predictive test. Preliminary results from the phase II randomized study (CO-HO-RT trial) evaluating the impact of concurrent or sequential letrozole and RT on toxicities has recently confirmed the need to identify hypersensitive patients before delivering concurrent systemic therapy with RT.