STAR-FISH in situ single-cell analysis in HER2-positive breast cancer patients undergoing neo-adjuvant chemotherapy treatment showed that: i) this treatment increased the proportion of cells displaying PIK3CA mutations; ii) PIK3CA mutations and HER2 amplification do not seem to be expressed in the same tumor cells; and, iii) treatment-associated changes in the spatial distribution of cellular genetic diversity correlated with long-term outcome following adjuvant therapy with trastuzumab [293]. This evidence concerns the gene ERBB2 and breast cancer.