A study derived from the GeparSepto trial, which screened a hotspot panel in 16 commonly mutated genes in all breast cancer subtypes and Copy Number Alterations (CNAs) in 8 cancer-relevant genes, concluded that the genes harboring the majority of genetic variants among the different subtypes were TP53 and PIK3CA. On the other hand, genetic heterogeneity in different breast cancer subtypes (Luminal/HER2− vs. HER2+ vs. TN) were related to differences in NAC response; TOP2A amplification was associated with a decrease in pCR in the TN cohort (multivariate p < 0.006). The gene discussed is TP53; the disease is breast cancer.