Your browser doesn't support javascript.
loading
Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies.
Wolf, Denise M; Yau, Christina; Wulfkuhle, Julia; Brown-Swigart, Lamorna; Gallagher, Rosa I; Lee, Pei Rong Evelyn; Zhu, Zelos; Magbanua, Mark J; Sayaman, Rosalyn; O'Grady, Nicholas; Basu, Amrita; Delson, Amy; Coppé, Jean Philippe; Lu, Ruixiao; Braun, Jerome; Asare, Smita M; Sit, Laura; Matthews, Jeffrey B; Perlmutter, Jane; Hylton, Nola; Liu, Minetta C; Pohlmann, Paula; Symmans, W Fraser; Rugo, Hope S; Isaacs, Claudine; DeMichele, Angela M; Yee, Douglas; Berry, Donald A; Pusztai, Lajos; Petricoin, Emanuel F; Hirst, Gillian L; Esserman, Laura J; van 't Veer, Laura J.
Afiliação
  • Wolf DM; Department of Laboratory Medicine, University of California, San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA. Electronic address: denise.wolf@ucsf.edu.
  • Yau C; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: cyau@buckinstitute.org.
  • Wulfkuhle J; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.
  • Brown-Swigart L; Department of Laboratory Medicine, University of California, San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.
  • Gallagher RI; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.
  • Lee PRE; Department of Laboratory Medicine, University of California, San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.
  • Zhu Z; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Magbanua MJ; Department of Laboratory Medicine, University of California, San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.
  • Sayaman R; Department of Laboratory Medicine, University of California, San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.
  • O'Grady N; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Basu A; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Delson A; Breast Science Advocacy Core, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Coppé JP; Department of Laboratory Medicine, University of California, San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.
  • Lu R; Quantum Leap Healthcare Collaborative, San Francisco, CA 94118, USA.
  • Braun J; Quantum Leap Healthcare Collaborative, San Francisco, CA 94118, USA.
  • Asare SM; Quantum Leap Healthcare Collaborative, San Francisco, CA 94118, USA.
  • Sit L; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Matthews JB; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Perlmutter J; Gemini Group, Ann Arbor, MI 48107, USA.
  • Hylton N; Department of Radiology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Liu MC; Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA.
  • Pohlmann P; MedStar Georgetown University Hospital, Georgetown University, Washington, DC 20057, USA.
  • Symmans WF; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Rugo HS; Division of Hematology/Oncology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Isaacs C; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA.
  • DeMichele AM; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Yee D; Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Berry DA; Berry Consultants, LLC, Austin, TX 78746, USA.
  • Pusztai L; Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
  • Petricoin EF; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.
  • Hirst GL; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Esserman LJ; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
  • van 't Veer LJ; Department of Laboratory Medicine, University of California, San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA. Electronic address: laura.vantveer@ucsf.edu.
Cancer Cell ; 40(6): 609-623.e6, 2022 06 13.
Article em En | MEDLINE | ID: mdl-35623341
ABSTRACT
Using pre-treatment gene expression, protein/phosphoprotein, and clinical data from the I-SPY2 neoadjuvant platform trial (NCT01042379), we create alternative breast cancer subtypes incorporating tumor biology beyond clinical hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status to better predict drug responses. We assess the predictive performance of mechanism-of-action biomarkers from ∼990 patients treated with 10 regimens targeting diverse biology. We explore >11 subtyping schemas and identify treatment-subtype pairs maximizing the pathologic complete response (pCR) rate over the population. The best performing schemas incorporate Immune, DNA repair, and HER2/Luminal phenotypes. Subsequent treatment allocation increases the overall pCR rate to 63% from 51% using HR/HER2-based treatment selection. pCR gains from reclassification and improved patient selection are highest in HR+ subsets (>15%). As new treatments are introduced, the subtyping schema determines the minimum response needed to show efficacy. This data platform provides an unprecedented resource and supports the usage of response-based subtypes to guide future treatment prioritization.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article