Intratumoral heterogeneity subclonal driver mutations that govern tumor metabolism have been identified in breast cancer (TP53, SMAD4) (238), consistent with studies of subclonal diversification of primary breast cancer revealed by multi region sequencing of the coding region (238), the non-coding region (242) and evidence for further genetic evolution upon relapse (SWI-SNF and JAK2-STAT3) (243). This evidence concerns the gene STAT3 and breast carcinoma.