Title | Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Wolf, DM, Yau, C, Wulfkuhle, J, Brown-Swigart, L, Gallagher, RI, Lee, PRong Evely, Zhu, Z, Magbanua, MJ, Sayaman, R, O'Grady, N, Basu, A, Delson, A, Coppé, JPhilippe, Lu, R, Braun, J, Asare, SM, Sit, L, Matthews, JB, Perlmutter, J, Hylton, N, Liu, MC, Pohlmann, P, W Symmans, F, Rugo, HS, Isaacs, C, DeMichele, AM, Yee, D, Berry, DA, Pusztai, L, Petricoin, EF, Hirst, GL, Esserman, LJ, Veer, LJ van 't |
Corporate Authors | |
Journal | Cancer Cell |
Volume | 40 |
Issue | 6 |
Pagination | 609-623.e6 |
Date Published | 2022 Jun 13 |
ISSN | 1878-3686 |
Keywords | Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Breast Neoplasms, Female, Humans, Neoadjuvant Therapy, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone |
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. |
DOI | 10.1016/j.ccell.2022.05.005 |
Alternate Journal | Cancer Cell |
PubMed ID | 35623341 |
PubMed Central ID | PMC9426306 |
Grant List | UL1 TR001863 / TR / NCATS NIH HHS / United States P30 CA082103 / CA / NCI NIH HHS / United States U54 HG007990 / HG / NHGRI NIH HHS / United States P30 CA016672 / CA / NCI NIH HHS / United States R01 CA255442 / CA / NCI NIH HHS / United States P01 CA210961 / CA / NCI NIH HHS / United States U54 CA209891 / CA / NCI NIH HHS / United States |