Background: The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status.
Methods: The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18-90 years who received neoadjuvant chemotherapy and had clinical and genomic data available. Chemosensitivity and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed. In a post hoc subanalysis, results were stratified by age (≤ 50 vs. > 50 years) and menopausal status in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) tumors.
Results: MammaPrint and BluePrint further classified 23% of tumors to a different subtype compared with immunohistochemistry, with more precise correspondence to pCR rates. Five-year DMFS and OS were highest in MammaPrint Low Risk, Luminal A-type and HER2-type tumors, and lowest in MammaPrint High Risk, Luminal B-type and Basal-type tumors. There was no significant difference in chemosensitivity between younger and older patients with Low-Risk (2.2% vs. 3.8%; p = 0.64) or High-Risk tumors (14.5% vs. 11.5%; p = 0.42), or within each BluePrint subtype; this was similar when stratifying by menopausal status. The 5-year outcomes were comparable by age or menopausal status for each molecular subtype.
Conclusion: Intrinsic preoperative chemosensitivity and long-term outcomes were precisely determined by BluePrint and MammaPrint regardless of patient age, supporting the utility of these assays to inform treatment and surgical decisions in early-stage breast cancer.
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http://dx.doi.org/10.1245/s10434-022-11666-2 | DOI Listing |
JCI Insight
January 2025
Department of Biomedical Engineering, Oregon Health and Science University, Portland, United States of America.
Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Laboratory of Translational Oncology and Translational Cancer Therapeutics, Warren Alpert Medical School of Brown University, Providence, United States of America.
Radiotherapy can be limited by pneumonitis which is impacted by innate immunity, including pathways regulated by TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from toxic effects of radiation and found two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) and oral TRAIL-Inducing Compound (TIC10/ONC201) could reduce pneumonitis, alveolar-wall thickness, and oxygen desaturation. Lung protection extended to late effects of radiation including less fibrosis at 22-weeks in TLY012-rescued survivors versus un-rescued surviving irradiated-mice.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Department of Laboratory Medicine, Division of Translational Cancer Researc, Lund University Cancer Centre, Lund University, Lund, Sweden.
The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated macrophages (TAMs) that, by virtue of their unanticipated Acvrl1 expression, are effector targets for adjuvant anti-angiogenic immunotherapy in mouse models of metastatic breast cancer. The combinatorial benefit depended on ALK1-mediated modulation of the differentiation potential of bone marrow-derived granulocyte-macrophage progenitors, the release of CD14+ monocytes into circulation, and their eventual extravasation.
View Article and Find Full Text PDFBreast Cancer
January 2025
Division of Breast and Endocrine Surgery, Department of Surgery, School of Medicine, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
Purpose: The aim of this study was to examine the clinical utility of tumor-infiltrating lymphocytes (TILs) evaluated by "average" and "hot-spot" methods in breast cancer patients.
Methods: We examined 367 breast cancer patients without neoadjuvant chemotherapy (NAC) by average and hot-spot methods to determine the consistency of TIL scores between biopsy and surgical specimens. TIL scores before NAC were also compared with the pathological complete response (pCR) rate and clinical outcomes in 144 breast cancer patients that received NAC.
Breast Cancer
January 2025
Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Exosome markers, CD63 and CD81, belong to the tetraspanin family and are expressed in solid tumors. It has been reported that these tetraspanin family members are prognostic factors in some cancers. However, the expression of CD63 and CD81 in pathological breast cancer specimens has not been reported.
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