title: The Hippo transducer TAZ as a biomarker of pathological complete response in HER2-positive breast cancer patients treated with trastuzumab-based neoadjuvant therapy.
abstract: Activation of the Hippo transducer TAZ is emerging as a novel oncogenic route in breast cancer and it has been associated with breast cancer stem cells. Additionally, TAZ expression has been linked with HER-2 positivity. We investigated the association between TAZ expression and pathological complete response in HER2-positive breast cancer patients treated with trastuzumab-based neoadjuvant therapy.TAZ was assessed in diagnostic core biopsies by immunohistochemistry. To categorize samples with low TAZ and samples with high TAZ we generated a score by combining staining intensity and cellular localization. The pathological complete response rate was 78.6% in patients with low TAZ tumors and 57.6% in patients with high TAZ tumors (p=0.082). In HER2-enriched tumors there was no significant association between TAZ and pathological complete response, whereas in the luminal B subtype the pathological complete response rate was 82.4% in tumors with low TAZ and 44.4% in tumors with high TAZ (p=0.035). This association remained statistically significant when restricting our analysis to triple-positive tumors with expression of both estrogen receptor and progesterone receptor ≥ 50% (p=0.035). Results from this exploratory study suggest that the TAZ score efficiently predicts pathological complete response in Luminal B, HER2-positive breast cancer patients who received neoadjuvant chemotherapy and trastuzumab.
authors.affiliation: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy. These authors contributed equally to this work.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy. These authors contributed equally to this work.
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.affiliation: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pizzuti
authors.affiliation: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy. Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Barba
authors.affiliation: Biostatistics-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sperati
authors.affiliation: Biostatistics-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Terrenato
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Benedetto
authors.affiliation: Department of Experimental and Clinical Sciences, University "G. d'Annunzio", Chieti, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.affiliation: Medical Oncology Unit, ASL Frosinone, Frosinone, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gamucci
authors.affiliation: Division of Pathology, 'SS. Annunziata' Hospital, Chieti, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Angelucci
authors.affiliation: Division of Pathology, ASL Frosinone, Frosinone, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ramieri
authors.affiliation: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Lauro
authors.affiliation: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Sergi
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Bartucci
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Dattilo
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pagliuca
authors.affiliation: Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
authors.affiliation: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy. Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maugeri-Saccà
mesh_terms: D000217:Acyltransferases; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D000217:Acyltransferases; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D014157:Transcription Factors; D000068878:Trastuzumab; C108675:TAFAZZIN protein, human; C508053:ERBB2 protein, human