ERBB2 and neoplasm: This phenomenon was investigated prospectively in a single-arm Phase 2 neoadjuvant study of T-DM1 plus pertuzumab.50 Among the ten (out of 157 evaluable) patients in this trial determined to exhibit intra-tumour HER2 heterogeneity (defined as either HER2 positivity by FISH in 5–50% of tumour cells in at least one of six cores per tumour, or presence of a HER2-negative tumour area), none showed pathological complete responses (pCR), meeting the primary endpoint for this association.