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Background: Recent data showed benefit of the addition of immune checkpoint inhibitor (ICI) therapy to cytotoxic chemotherapy in the neoadjuvant setting for patients with early triple negative breast cancer. Acute presentations in patients treated with ICI therapy and combined chemotherapy/ICI therapy can be challenging and have significant resource implications.
Materials And Methods: A prospective analysis was performed at a specialist oncology hospital in England from December 1, 2022 to December 31, 2024. The primary outcome measure was whether the acute presentation was due to an ICI-related toxicity. Secondary outcome measures were number of inpatient bed days and the proportion of patients with grade ≥3 diarrhoea or transaminases that were diagnosed with ICI-related toxicity.
Results: During the study period, 285 patients were treated with neoadjuvant PC-EC/Pembro for triple negative breast cancer with 210 emergency presentations in 168 patients to the acute floor. Fifty-three (25.2 %) patients were diagnosed with an ICI-related toxicity of which 5 were a relapsed/recurrent presentation. One hundred and nine patients (51.9 %) were discharged on the day of presentation. A total of 576 inpatient bed days were used in the management of the cohort. Sixteen (7.6 %) patients had grade 3 diarrhoea at presentation; only 5 (31.3 %) of these were ICI-mediated. Eleven (5.2 %) patients had a grade ≥3 ALT rise at presentation; only 3 (27.2 %) of these were ICI-mediated.
Conclusion: In triple negative breast cancer being treated in the neoadjuvant setting with chemotherapy/immune checkpoint inhibition only 25.2 % of acute presentations had an ICI-related toxicity driving their attendance. Toxicities in this cohort may require a different approach to those treated with chemotherapy or ICI alone and may necessitate new clinical practice guidance.
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http://dx.doi.org/10.1016/j.breast.2025.104536 | DOI Listing |
J Med Chem
September 2025
Department of Natural Products and Medicinal Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
Nitric oxide (NO) is a multifunctional signaling molecule in oncology, influencing tumor progression, apoptosis, and immune responses. In contrast, chlorambucil (Cbl), a DNA-alkylating chemotherapeutic, induces cytotoxicity through DNA damage. Here, we report a photoresponsive nanoparticle platform for sequential codelivery of NO and Cbl, where NO is released within 10 min of irradiation, followed by Cbl release within 30 min.
View Article and Find Full Text PDFBreast Cancer Res Treat
September 2025
Department of Pharmacy, Duke University Hospital, Durham, NC, USA.
Purpose: Limited data is available assessing sequencing of antibody drug conjugates (ADCs) in patients with hormone receptor-positive (HR +), human epidermal growth factor 2 (HER2)-negative, HER2-low, and triple-negative metastatic breast cancer (MBC), including patients with brain metastases (BrM) or leptomeningeal disease (LMD). This study assesses the efficacy and safety of sequential sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) in MBC and impact on chemotherapy (CTX).
Methods: This is a single-center, retrospective, cohort study in adult patients with HR + , HER2-negative, or low MBC who received T-DXd and/or SG.
Oncogene
September 2025
Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Cholesterol biosynthesis is more activated in triple negative breast cancer (TNBC) than in other subtype breast cancer and plays essential role in facilitating TNBC. However, the regulatory network and how cholesterol biosynthesis contribute to TNBC development and progression are not well elucidated. Here, we found that reticulum membrane protein complex 2 (EMC2) is highly expressed in TNBC and predicts short survival of patients.
View Article and Find Full Text PDFMethods Cell Biol
September 2025
LR18ES03 Laboratory of Neurophysiology, Cellular Physiopathology and Valorisation of Biomolecules, Faculty of Science of Tunis, University Tunis El Manar, Tunis, Tunisia. Electronic address:
Breast cancer (BC) represents a major socio-economic challenge worldwide due to its high morbidity and mortality rates. Despite various therapeutic strategies, the heterogeneity of breast cancer and the resistance of tumour cells often lead to treatment failure. Consequently, the use of animal models of BC is crucial for understanding the cellular and molecular mechanisms involved in the different stages of carcinogenesis and for screening new drugs to assess their efficacy, potential safety and side effects.
View Article and Find Full Text PDFCell Signal
September 2025
School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, People's Republic of China.
Triple-negative breast cancer (TNBC) presents a formidable therapeutic challenge due to its aggressive behavior, molecular heterogeneity, and lack of actionable targets. This study identifies activation-induced cytidine deaminase (AID) as a pivotal epigenetic driver reprogramming the tumor microenvironment (TME) via non-canonical regulation of NOTCH signaling. Mechanistically, AID recruits histone acetyltransferase 1 (HAT1) to form a chromatin-remodeling complex that binds the JAG1 promoter region (-1.
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