Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer

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Abstract

PIK3CA mutations occur in approximately 40% of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. The PI3Kα-specific inhibitor alpelisib has shown antitumor activity in early studies.

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Most cited references 4

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Phosphatidylinositol 3-Kinase, Growth Disorders, and Cancer

Marcus D. Goncalves, Benjamin D Hopkins, Lewis Cantley (2018)

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Nicholas Turner, Patrick Neven, Sibylle Loibl … (2017)

Oestrogen-receptor-positive breast cancer is the most common subtype of breast cancer. Endocrine therapies that target the dependence of this subtype on the oestrogen receptor have substantial activity, yet the development of resistance to therapy is inevitable in advanced cancer. Major progress has been made in identifying the drivers of oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into major advances in the treatment of advanced breast cancer, with several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of mTOR and inhibitors of the cyclin-dependent kinases CDK4 and CDK6 substantially improve progression-free survival. A new wave of targeted therapies is being developed, including inhibitors of PI3K, AKT, and HER2, and a new generation of oestrogen-receptor degraders. Considerable challenges remain in patient selection, deciding on the most appropriate order in which to administer therapies, and establishing whether cross-resistance occurs between therapies.

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Treatment for the endocrine resistant breast cancer: Current options and future perspectives

Ling-Ming Tseng, Tzu-Ting Huang, Karineh Petrossian … (2017)

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Author and article information

Journal

Title: New England Journal of Medicine

Abbreviated Title: N Engl J Med

Publisher: Massachusetts Medical Society

ISSN (Print): 0028-4793

ISSN (Electronic): 1533-4406

Publication date Created: May 16 2019

Publication date (Print): May 16 2019

Volume: 380

Issue: 20

Pages: 1929-1940

Affiliations

[1 ]From Institut Gustave Roussy, INSERM Unité 981, Université Paris-Sud, Villejuif (F.A.), Institut de Cancérologie de l’Ouest, St. Herblain (M.C.), and Novartis Pharma, Paris (A.-S.L.) — all in France; Hospital Universitario 12 de Octubre, Madrid (E.C.); National Institute of Oncology (G.R.) and Duna Medical Center (Z.P.), Budapest, Hungary; German Breast Group, Neu-Isenburg, and Center for Hematology and Oncology Bethanien, Frankfurt — both in Germany (S.L.); UCSF Helen Diller Family Comprehensive Cancer...