New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?pi.
Essia Mezni,Cecile Vicier,Mathilde Guerin,Renaud Sabatier,François Bertucci,Anthony Gonçalves +5 more
TLDR
Questions remain unresolved, like the optimal management of HER2-positive/HR-positive advanced breast cancer and the identification of predictive biomarkers to better define populations that can benefit most from these new therapies and approaches.Abstract:
Over the last few decades, improved knowledge of oncogenic activation mechanisms of HER2 protein has led to the development of HER2 targeted therapies that are currently commonly used in HER2-positive advanced breast cancer, such as trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine. The management of this breast cancer subgroup has thus been revolutionized and its prognosis has changed dramatically. Nevertheless, HER2-positive advanced breast cancer remains an incurable disease and resistance to conventional anti-HER2 drugs is almost unavoidable. Nowadays, biochemical and pharmaceutical advances are meeting the challenge of developing increasingly sophisticated therapies directed against HER2, including novel anti HER2 antibodies with increased affinity. New antibody-drug conjugates (ADC) with more advanced pharmacological properties, and dual targeting of epitopes via bispecific monoclonal antibodies are also emerging. In addition, more potent and more specific HER2 tyrosine kinase inhibitors have shown interesting outcomes and are under development. Finally, researchers’ interest in tumor microenvironment, particularly tumor-infiltrating lymphocytes, and the major role that signaling pathways, such as the PI3K/AKT/mTOR pathway, play in the development of resistance to anti-HER2 therapies have spurred the development of clinical trials evaluating innovative combinations of anti-HER2 with PD-1/PDL-1, CDK4/6 and PI3K inhibitors. However, several questions remain unresolved, like the optimal management of HER2-positive/HR-positive advanced breast cancer and the identification of predictive biomarkers to better define populations that can benefit most from these new therapies and approaches.read more
Citations
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Fatima Cardoso,Ana Costa,Elżbieta Senkus,Matti Aapro,Fabrice Andre,Carlos H. Barrios,Jonas Bergh,G. Bhattacharyya,Laura Biganzoli,Maria João Cardoso,Lisa A. Carey,D. Corneliussen-James,Giuseppe Curigliano,Véronique Diéras,N.S. El Saghir,Alex Eniu,Lesley Fallowfield,D. Fenech,Prudence A. Francis,Karen A. Gelmon,Alessandra Gennari,Nadia Harbeck,Clifford A. Hudis,Bella Kaufman,Ian E. Krop,Musa Mayer,H. Meijer,Shirley Mertz,S. Ohno,Olivia Pagani,E. Papadopoulos,Fedro A. Peccatori,Frédérique Penault-Llorca,Martine Piccart,Jean-Yves Pierga,Hope S. Rugo,Lillie D. Shockney,George W. Sledge,Sandra M Swain,Christoph Thomssen,Andrew Tutt,Daniel A. Vorobiof,Binghe Xu,Larry Norton,Eric P. Winer +44 more
TL;DR: This ESO-ESMO ABC 5 Clinical Practice Guideline provides key recommendations for managing advanced breast cancer patients, and provides updates on managing patients with all breast cancer subtypes, LABC, follow-up, palliative and supportive care.