• Mashup Score: 2
    NKG2A is a Therapeutic Vulnerability in Immunotherapy Resistant MHC-I Heterogeneous Triple Negative Breast Cancer - 7 month(s) ago

    Abstract. Despite the success of immune checkpoint inhibition (ICI) in treating cancer, patients with triple-negative breast cancer (TNBC) often develop resistance to therapy, and the underlying mechanisms are unclear. MHC-I expression is essential for antigen presentation and T cell-directed immunotherapy responses. This study demonstrates that TNBC patients display intratumor heterogeneity in regional MHC-I expression. In murine models, loss of MHC-I negates anti-tumor immunity and ICI response, whereas intratumor MHC-I heterogeneity leads to increased infiltration of NK cells in IFNγ dependent manner. Using spatial technologies, MHC-I heterogeneity is associated with clinical resistance to anti-PD-L1 therapy and increased NK:T cell ratios in human breast tumors. MHC-I heterogeneous tumors require NKG2A to suppress NK cell function. Combining anti-NKG2A and anti-PD-L1 therapies restores complete response in heterogeneous MHC-I murine models, dependent on the presence of activated, tu

    Source: aacrjournals.org
    Categories: Hem/Onc News and Journals, Latest Headlines
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      CD_AACR

      OnlineFirst: NKG2A is a Therapeutic Vulnerability in #Immunotherapy Resistant MHC-I Heterogeneous Triple Negative #BreastCancer, by @BCT255, @SXPung, @BalkoLab et al. https://t.co/0YZRI5NkAH @VUMCDiscoveries #TNBC https://t.co/QOdgRgZ5vo

  • Mashup Score: 0
    A phase 1 trial of fuzuloparib in combination with apatinib for advanced ovarian and triple-negative breast cancer: efficacy, safety, pharmacokinetics and germline BRCA mutation analysis - BMC Medicine - 7 month(s) ago

    Background The effect of the combination of an anti-angiogenic agent with a poly (ADP-ribose) polymerase (PARP) inhibitor in cancer treatment is unclear. We assessed the oral combination of fuzuloparib, a PARP inhibitor, and apatinib, a VEGFR2 inhibitor for treating advanced ovarian cancer (OC) or triple-negative breast cancer (TNBC). Methods This dose-escalation and pharmacokinetics-expansion phase 1 trial was conducted in China. We used a standard 3 + 3 dose-escalation design, with 7 dose levels tested. Patients received fuzuloparib orally twice daily, and apatinib orally once daily. The study objectives were to determine the safety profile, recommended phase 2 dose (RP2D), pharmacokinetics, preliminary efficacy, and efficacy in relation to germline BRCA mutation (gBRCAmut). Results Fifty-two pre-treated patients were enrolled (30 OC/22 TNBC). 5 (9.6%) patients had complete response, 14 (26.9%) had partial response, and 15 (28.8%) had stable disease. Objective response rate (ORR) and

    Source: bmcmedicine.biomedcentral.com
    Categories: General Medicine Journals and Societies, Latest Headlines
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      BMCMedicine

      New findings from a phase 1 trial: #Fuzuloparib plus #apatinib had acceptable safety in patients with advanced #ovariancancer (OC) or triple-negative breast cancer (#TNBC): https://t.co/QI8AYj7lhR https://t.co/JIpSmZOW23

  • Mashup Score: 3
    New Challenge in Triple-Negative Breast Cancer: Optimizing the Sequencing of Treatments - The ASCO Post - 8 month(s) ago

    New approaches are offering hope for better outcomes in metastatic triple-negative breast cancer, according to Suchita Pakkala, MD, of Emory University’s Winship Cancer Institute, Atlanta. She shared her thoughts on using PARP inhibitors and antibody-drug conjugates at the 2023 Debates and Didactics in Hematology and Oncology Conference, sponsored annually by Winship, in Sea Island, Georgia. 1 “The study [DESTINY-Breast04] got a standing ovation at the 2022 ASCO Annual Meeting, and for good reason.” —

    Source: ascopost.com
    Categories: Hem/Onc News and Journals, Latest Headlines
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      ASCOPost

      New Challenge in Triple-Negative Breast Cancer: Optimizing the Sequencing of Treatments https://t.co/113dYKagXT #bcsm #breastcancer #TNBC #oncology

  • Mashup Score: 5
    Triple-negative Breast Carcinoma With Apocrine and... : The American Journal of Surgical Pathology - 9 month(s) ago

    ment of 18 non–high-grade TNBCs with apocrine and/or histiocytoid features. All were grade I or II with low Ki-67 (≤20%). Thirteen (72%) showed apocrine features, and 5 (28%) showed histiocytoid and lobular features. In all, 17/18 expressed the androgen receptor, and 13/13 expressed gross cystic disease fluid protein 15. Four (22.2%) patients were treated with neoadjuvant chemotherapy, but none achieved a pathologic complete response. In all, 2/18 patients (11%) had lymph node metastasis at the time of surgery. None of the cases had a recurrence or disease-specific death, with an average follow-up time of 38 months. Thirteen cases were profiled by targeted capture-based next-generation DNA sequencing. Genomic alterations (GAs) were most significant for PI3K-PKB/Akt pathway (69%) genes, including PIK3R1 (23%), PIK3CA (38%), and PTEN (23%), and RTK-RAS pathway (62%) including FGFR4 (46%) and ERBB2 (15%). TP53 GA was seen in only 31% of patients. Our findings support those on high-grade T

    Source: journals.lww.com
    Categories: Hem/Oncs, Latest Headlines
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      DrSGraff

      Sharing our latest work! Triple-negative Breast Carcinoma With Apocrine and Histiocytoid Features A Clinicopathologic and Molecular Study of 18 Cases @BrownUCancer @LiangChengMD #PathTwitter #bcsm #TNBC https://t.co/4ZdtbuzXxp

  • Mashup Score: 0
    HER2-Low Status Is ‘Dynamic’ for Patients With Triple-Negative Breast Cancer - The ASCO Post - 9 month(s) ago

    The probability of obtaining a HER2-low test result increases with the number of biopsies performed, according to a study of more than 500 biopsy samples in patients with triple-negative breast cancer. For patients originally labeled as having no HER2 expression (HER2 0), each successive biopsy rendered one-third of these patients HER2-low, potentially qualifying them for treatment with fam-trastuzumab deruxtecan-nxki (T-DXd). 1 “Our findings show that HER2 status is dynamic in patients with triple-negativ

    Source: ascopost.com
    Categories: Hem/Onc News and Journals, Latest Headlines
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      ASCOPost

      HER2-Low Status Is ‘Dynamic’ for Patients With Triple-Negative Breast Cancer https://t.co/zp7QdiMJ9r #bcsm #breastcancer #oncology #TNBC

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