Oncotarget

Clinical Research Papers:

The Hippo transducer TAZ as a biomarker of pathological complete response in HER2-positive breast cancer patients treated with trastuzumab-based neoadjuvant therapy

Patrizia Vici, Marcella Mottolese, Laura Pizzuti, Maddalena Barba, Francesca Sperati, Irene Terrenato, Anna Di Benedetto, Clara Natoli, Teresa Gamucci, Domenico Angelucci, Maria Teresa Ramieri, Luigi Di Lauro, Domenico Sergi, Monica Bartucci, Rosanna Dattilo, Alfredo Pagliuca, Ruggero De Maria and Marcello Maugeri-Saccà _

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Oncotarget. 2014; 5:9619-9625. https://doi.org/10.18632/oncotarget.2449

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Abstract

Patrizia Vici1,*, Marcella Mottolese2,*, Laura Pizzuti1, Maddalena Barba1,3, Francesca Sperati4, Irene Terrenato4, Anna Di Benedetto2, Clara Natoli5, Teresa Gamucci6, Domenico Angelucci7, Maria Teresa Ramieri8, Luigi Di Lauro1, Domenico Sergi1, Monica Bartucci9, Rosanna Dattilo10, Alfredo Pagliuca10, Ruggero De Maria3 and Marcello Maugeri-Saccà1,3

1 Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy

2 Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy

3 Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy

4 Biostatistics-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy

5 Department of Experimental and Clinical Sciences, University “G. d’Annunzio”, Chieti, Italy

6 Medical Oncology Unit, ASL Frosinone, Frosinone, Italy

7 Division of Pathology, ‘SS. Annunziata’ Hospital, Chieti, Italy

8 Division of Pathology, ASL Frosinone, Frosinone, Italy

9  Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA

10 Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

*  These authors contributed equally to this work

Correspondence:

Marcello Maugeri-Saccà, email:

Ruggero De Maria, email:

Keywords: Hippo pathway, TAZ, HER2-positive breast cancer, neoadjuvant therapy, pathological complete response

Received: July 31, 2014 Accepted: September 07, 2014 Published: September 08, 2014

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.


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