It is conceivable that the success of the current hormonal therapies for estrogen receptor positive (ER+) breast cancer, enhanced with the new generations of ER degraders, inhibitors of PI3k, AKT, etc. [23], as well as the effectiveness of new therapeutic strategies for the treatment of triple negative tumors [24], together with the improvement of the classic chemo and radiotherapeutic approaches, are among the reasons that have thus far discouraged the staging of clinical trials to assess the value of melatonin for BC treatment. This evidence concerns the gene ESR1 and breast carcinoma.