title: Human epidermal growth factor receptor 2 (HER2)-positive and hormone receptor-positive breast cancer: new insights into molecular interactions and clinical implications.
abstract: Recent data show a significant benefit from combining an anti-HER-2 agent with endocrine therapy in HER2-positive and hormone receptor (HR)-positive metastatic breast cancer. However, as the clinical outcomes achieved by these combinations do not favourably match those with chemotherapy, clinicians still perceive HER2-positive breast cancer as an homogeneous group and consider chemotherapy with anti-HER2 agents as the preferred treatment option, regardless of the HR status. Indeed, in HR-positive HER2-positive tumours, chemotherapy with anti-HER2 agents is the backbone of treatment, while endocrine therapy is commonly used in sequence when HR and HER2 are co-expressed rather than as a real alternative. Emerging biological and clinical data challenge this paradigm, suggesting that HER2-positive tumours are rather heterogeneous that HRs co-expression may account for part of this heterogeneity and, finally, that chemotherapy may represent an overtreatment in selected cases. The present review aims to summarise the biological features of HER2-positive breast cancer according to HR status, the role of the bi-directional cross-talk between HER2 and HR pathways on resistance development to anti-HER2 and endocrine therapy, and finally, the novel therapeutic strategies, including but not limited to chemotherapy, targeting these two pathways.
authors.affiliation: Unit of Investigative Clinical Oncology (INCO) and Division of Medical Oncology, Piedmont Oncology Foundation/Institute for Cancer Research and Treatment, Candiolo.
authors.forename: F
authors.initials: F
authors.lastname: Montemurro
authors.forename: S
authors.initials: S
authors.lastname: Di Cosimo
authors.forename: G
authors.initials: G
authors.lastname: Arpino
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: breast cancer; cancer metastasis; drug therapy; her2/neu; hormone receptors; resistance