Climent et al demonstrated recently that PER3 is underexpressed in estrogen receptor–positive patients with breast cancer and that loss of PER3 is closely associated with tumor recurrence, especially in the patients being treated with tamoxifen; moreover, mice with PER3 deficiency are found to be more susceptible to the invasive cancer.27 These data, coupled with the positive associations implicated in epidemiological studies, suggest that genetic variants in the PER3 gene may be genetic susceptibility biomarkers and play a key role in oncogenesis. This evidence concerns the gene ESR1 and breast carcinoma.