Interestingly, only 15% of the cases overexpressing CLN3 and lacking HER2 receptor are triple negative (HER2/ER/PR negative) and 85% are ER/PR positive, indicating that up-regulated CLN3 could be a good prognostic factor in HER2-negative breast cancers, suggesting a broad application of CLN3 targeted therapies in breast cancers that do not overexpress HER2. This evidence concerns the gene ESR1 and breast cancer.