1. Clinical significance and biology of circulating tumor DNA in high-risk early-stage HER2-negative breast cancer receiving neoadjuvant chemotherapy
- Author
-
Magbanua, Mark Jesus M, Brown Swigart, Lamorna, Ahmed, Ziad, Sayaman, Rosalyn W, Renner, Derrick, Kalashnikova, Ekaterina, Hirst, Gillian L, Yau, Christina, Wolf, Denise M, Li, Wen, Delson, Amy L, Asare, Smita, Liu, Minetta C, Albain, Kathy, Chien, A Jo, Forero-Torres, Andres, Isaacs, Claudine, Nanda, Rita, Tripathy, Debu, Rodriguez, Angel, Sethi, Himanshu, Aleshin, Alexey, Rabinowitz, Matthew, Perlmutter, Jane, Symmans, W Fraser, Yee, Douglas, Hylton, Nola M, Esserman, Laura J, DeMichele, Angela M, Rugo, Hope S, and van 't Veer, Laura J
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer Genomics ,Clinical Trials and Supportive Activities ,Cancer ,Genetics ,Women's Health ,Breast Cancer ,Human Genome ,Clinical Research ,Good Health and Well Being ,Humans ,Female ,Breast Neoplasms ,Triple Negative Breast Neoplasms ,Circulating Tumor DNA ,Neoadjuvant Therapy ,Clinical Relevance ,Antineoplastic Combined Chemotherapy Protocols ,Biology ,Receptor ,ErbB-2 ,Receptor ,erbB-2 ,circulating tumor DNA ,gene expression ,neoadjuvant chemotherapy ,pathologic complete response ,receptor subtype ,residual cancer burden ,Neurosciences ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized ctDNA analysis in hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NAC) in the I-SPY2 trial. ctDNA positivity rates before, during, and after NAC are higher in TNBC than in HR-positive/HER2-negative breast cancer patients. Early clearance of ctDNA 3 weeks after treatment initiation predicts a favorable response to NAC in TNBC only. Whereas ctDNA positivity associates with reduced distant recurrence-free survival in both subtypes. Conversely, ctDNA negativity after NAC correlates with improved outcomes, even in patients with extensive residual cancer. Pretreatment tumor mRNA profiling reveals associations between ctDNA shedding and cell cycle and immune-associated signaling. On the basis of these findings, the I-SPY2 trial will prospectively test ctDNA for utility in redirecting therapy to improve response and prognosis.
- Published
- 2023