As the majority of BRCA1 cancers are ER-, there is also recent evidence suggesting that E3 ubiquitin-ligases (related family of RNF146, a candidate gene in 6q22.33) and BRCA1 may act in conjunction to regulate ER-mediated pathways in breast cancer tumorigenesis [20], [21]. This evidence concerns the gene ESR1 and breast carcinoma.