Concurrent or sequential letrozole with adjuvant breast radiotherapy: primetime for personalized radiation oncology

We would like to thank both Kaidar-Person (1) and Meattini (2) for their very constructive and positive commentaries. As mentioned by Kaidar-Person (1), efficacy of adjuvant breast cancer radiotherapy after breast conserving surgery is well established since many years by reducing both breast recurrences and breast cancer death (3). In addition to radiation therapy, endocrine treatment [tamoxifen and aromatase inhibitor (AI)] also significantly reduced recurrence and 10-year breast cancer mortality rate (4). The ideal sequence of endocrine therapy and radiation (concurrent or sequential use) was prospectively assessed in the CO-HO-RT randomized study (5). This clinical trial was designed to evaluate the risk of radio-induced subcutaneous fibrosis (RISF) occurrence (primary endpoint) between the two arms but no significant RISF difference was observed between concurrent or sequential arms with long-term follow-up (6). Therefore, even though letrozole showed radiosensitization properties regarding human breast cancer cell-lines (7), some recent preclinical data displayed a reduction of lung fibrosis when combined to radiation (8). Indeed, clinical data confirmed that concurrent AI and radiotherapy do not increase late toxicities (6). In addition, a large and exhaustive literature review was recently published and reported no difference in esthetic outcome or toxicities between sequential or concomitant endocrine treatment, regardless tamoxifen or AI use (9).