All biomarker subgroups associated with higher HER2 amplification or expression (HER2 IHC3+, HER2/CEP17 gene ratio ≥ 4, HER2 mRNA expression > median, and homogeneous HER2 IHC expression) showed numerically higher pCR rates compared with subgroups with lower HER2 levels, irrespective of treatment arm...Although our biomarker analysis did not identify a subgroup of patients that benefited from neoadjuvant T-DM1 + P versus TCH + P, the data revealed that patients with higher HER2 amplification/expression and immune marker levels had improved response irrespective of treatment arm. These analyses confirm the role of HER2 tumor biology and the immune microenvironment in influencing pCR in the neoadjuvant setting and reaffirm the molecular diversity of HER2-positive breast cancer.

...Rate of Pathologic Complete Response (pCR) by HER2 Amplification Status Non-Heterogeneous...

...Second-line, standard-of-care treatment with T-DM1 shouldn’t have been started yet at the time of patient enrollment4.Willingness and ability to comply with the prescribed ART intake, the scheduled visits, treatment plans, laboratory tests and other procedures5.Archival tumor samples must be obtained from primary and/or metastatic sites: representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks or at least 20 unstained slides 6.Histologically confirmed diagnosis of invasive HER2+ BC, as defined by an IHC score of 3+ and/or HER2 gene amplification by ISH techniques, as defined by an HER2/CEP17 ratio = 2.0 and/or an average HER2 gene copy number = 4.0 signals/cell 7.Prior first-line treatment for advanced HER2+ BC in the unresectable locally advanced or metastatic settings (LABC/MBC) must consist of taxane plus trastuzumab plus pertuzumab 8.Disease progression must have occurred during first-line treatment for unresectable LABC or MBC 9.Patients must have measurable disease that is evaluable per RECIST v1.110.Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 and life expectancy > 2 months.11.Adequate hematologic and organ function, as evidenced by the following local laboratory results:a.Absolute neutrophil count > 1500 cells/ microL; b.Platelet count > 100.000/ microL; c.Haemoglobin > 9.0 g/dL;d.AST, ALT, and alkaline phosphatase < 2.5 the upper limit of normal (ULN) e.Total bilirubin < 1.5 the ULN f.Serum creatinine < 1.1 mg/dl12.Full recovery from previous treatment-related toxicity (with the exception of G1 peripheral neurotoxicity and of other toxicities that are not included in the Exclusion criteria and that are not in contrast with inclusion criteria)13.Negative serum pregnancy test for pre-menopausal women and for women less than 12 months after the onset of menopause14.Female patients of childbearing potential must agree to sexual abstinence or to use two highly effective methods of contraception throughout the study and for at least six months after the end of the study. ...