The Impact of the Hippo Pathway and Cell Metabolism on Pathological Complete Response in Locally Advanced Her2+ Breast Cancer: The TRISKELE Multicenter Prospective Study.

Autor:	Krasniqi E; Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Di Lisa FS; Phase IV Clinical Studies Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Di Benedetto A; Pathology Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Barba M; Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Pizzuti L; Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Filomeno L; Phase IV Clinical Studies Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Ercolani C; Pathology Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Tinari N; Department of Medical, Oral and Biotechnological Sciences, Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, 66100 Chieti, Italy., Grassadonia A; Department of Innovative Technologies in Medicine and Dentistry, Centre for Advanced Studies and Technology (CAST), G. D'Annunzio University, 66100 Chieti, Italy., Santini D; 'Sapienza' University of Rome, Polo Pontino, 04011 Aprilia, Italy., Minelli M; Division of Oncology, San Giovanni Hospital, 00184 Rome, Italy., Montemurro F; Breast Unit, Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia-IRCCS (Istituti di Ricovero e Cura a Carattere Scientifico), 10060 Candiolo, Italy., Fabbri MA; Medical Oncology Unit, Belcolle Hospital, 01100 Viterbo, Italy., Mazzotta M; Medical Oncology Unit, Belcolle Hospital, 01100 Viterbo, Italy., Gamucci T; Medical Oncology, Sandro Pertini Hospital, 00157 Rome, Italy., D'Auria G; Medical Oncology, Sandro Pertini Hospital, 00157 Rome, Italy., Botti C; Department of Surgery, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Pelle F; Department of Surgery, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Cavicchi F; Department of Surgery, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Cappelli S; Department of Surgery, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Cappuzzo F; Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Sanguineti G; Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Tomao S; Department of Radiological, Oncological and Anatomo-Pathological Sciences, 'Sapienza' University of Rome, 00185 Rome, Italy., Botticelli A; Department of Radiological, Oncological and Anatomo-Pathological Sciences, 'Sapienza' University of Rome, 00185 Rome, Italy., Marchetti P; Istituto Dermopatico dell'Immacolata, IDI-IRCCS, 00167 Rome, Italy., Maugeri-Saccà M; Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.; Clinical Trial Center, Biostatistics and Bioinformatics, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., De Maria R; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.; Fondazione Policlinico Universitario 'A. Gemelli', IRCCS (Istituti di Ricovero e Cura a Carattere Scientifico), 00168 Rome, Italy., Ciliberto G; Scientific Direction, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Sperati F; Clinical Trial Center, Biostatistics and Bioinformatics, San Gallicano Dermatological Institute IRCCS, 00144 Rome, Italy., Vici P; Phase IV Clinical Studies Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.
Jazyk:	angličtina
Zdroj:	Cancers [Cancers (Basel)] 2022 Oct 03; Vol. 14 (19). Date of Electronic Publication: 2022 Oct 03.
DOI:	10.3390/cancers14194835
Abstrakt:	The Hippo pathway and its two key effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are consistently altered in breast cancer. Pivotal regulators of cell metabolism such as the AMP-activated protein kinase (AMPK), Stearoyl-CoA-desaturase 1 (SCD1), and HMG-CoA reductase (HMGCR) are relevant modulators of TAZ/YAP activity. In this prospective study, we measured the tumor expression of TAZ, YAP, AMPK, SCD1, and HMGCR by immunohistochemistry in 65 Her2+ breast cancer patients who underwent trastuzumab-based neoadjuvant treatment. The aim of the study was to assess the impact of the immunohistochemical expression of the Hippo pathway transducers and cell metabolism regulators on pathological complete response. Low expression of cytoplasmic TAZ, both alone and in the context of a composite signature identified by machine learning including also low nuclear levels of YAP and HMGCR and high cytoplasmic levels of SCD1, was a predictor of residual disease in the univariate logistic regression. This finding was not confirmed in the multivariate model including estrogen receptor > 70% and body mass index > 20. However, our findings were concordant with overall survival data from the TCGA cohort. Our results, possibly affected by the relatively small sample size of this study population, deserve further investigation in adequately sized, ad hoc prospective studies.
Databáze:	MEDLINE
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