29,174 results on '"Receptor, ErbB-2"'
Search Results
2. Noninvasive identification of HER2-low-positive status by MRI-based deep learning radiomics predicts the disease-free survival of patients with breast cancer.
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Guo, Yuan, Xie, Xiaotong, Tang, Wenjie, Chen, Siyi, Wang, Mingyu, Fan, Yaheng, Lin, Chuxuan, Hu, Wenke, Yang, Jing, Xiang, Jialin, Jiang, Kuiming, Wei, Xinhua, Huang, Bingsheng, and Jiang, Xinqing
- Subjects
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PROGRESSION-free survival , *OVERALL survival , *RADIOMICS , *DEEP learning , *EPIDERMAL growth factor receptors - Abstract
Objective: This study aimed to establish a MRI-based deep learning radiomics (DLR) signature to predict the human epidermal growth factor receptor 2 (HER2)-low-positive status and further verified the difference in prognosis by the DLR model. Methods: A total of 481 patients with breast cancer who underwent preoperative MRI were retrospectively recruited from two institutions. Traditional radiomics features and deep semantic segmentation feature-based radiomics (DSFR) features were extracted from segmented tumors to construct models separately. Then, the DLR model was constructed to assess the HER2 status by averaging the output probabilities of the two models. Finally, a Kaplan‒Meier survival analysis was conducted to explore the disease-free survival (DFS) in patients with HER2-low-positive status. The multivariate Cox proportional hazard model was constructed to further determine the factors associated with DFS. Results: First, the DLR model distinguished between HER2-negative and HER2-overexpressing patients with AUCs of 0.868 and 0.763 in the training and validation cohorts, respectively. Furthermore, the DLR model distinguished between HER2-low-positive and HER2-zero patients with AUCs of 0.855 and 0.750, respectively. Cox regression analysis showed that the prediction score obtained using the DLR model (HR, 0.175; p = 0.024) and lesion size (HR, 1.043; p = 0.009) were significant, independent predictors of DFS. Conclusions: We successfully constructed a DLR model based on MRI to noninvasively evaluate the HER2 status and further revealed prospects for predicting the DFS of patients with HER2-low-positive status. Clinical relevance statement: The MRI-based DLR model could noninvasively identify HER2-low-positive status, which is considered a novel prognostic predictor and therapeutic target. Key Points: • The DLR model effectively distinguished the HER2 status of breast cancer patients, especially the HER2-low-positive status. • The DLR model was better than the traditional radiomics model or DSFR model in distinguishing HER2 expression. • The prediction score obtained using the model and lesion size were significant independent predictors of DFS. [ABSTRACT FROM AUTHOR]
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- 2024
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3. A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Potential Anti-tumor Effects of SSGJ-705 in Patients With Advanced or Metastatic HER2-expressing Solid Tumors
- Published
- 2021
4. Age‐specific impacts of nicotine and withdrawal on hippocampal neuregulin signalling.
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Keady, Jack, Fisher, Miranda, Anderson, Erin, LeMalefant, Rachel, and Turner, Jill
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NEUREGULINS , *NICOTINE , *SMOKING cessation , *PROTEIN-tyrosine kinases , *HIPPOCAMPUS (Brain) - Abstract
Smoking remains the leading cause of preventable death in the United States, with 87% of smokers starting before the age of 18. Age of initiation is a major predictive factor for smoking frequency and successful smoking cessation. People who initiate smoking during adolescences are 2.33 times more likely to become heavy smokers and half as likely to quit compared with smokers who started during adulthood. Additionally, schizophrenia, a disease state linked to altered neurodevelopment during adolescence, is a major predictive factor for smoking status. Smoking rates among people suffering from schizophrenia are between 60% and 90%. Interestingly, the Neuregulin Signalling Pathway (NSP), which plays an important role in neurodevelopment, is implicated in both schizophrenia and nicotine use disorder. Specifically, SNPS in neuregulin 3 (Nrg3) and Erb‐B2 Receptor Tyrosine Kinase 4 (ErbB4) have been associated with smoking cessation outcomes and schizophrenia. Here, we examine the effects of chronic nicotine (18 mg/kg/day) and 24‐h withdrawal on NSP gene expression in the hippocampus of adult (20‐week‐old) and adolescent (4‐week‐old) mice. We show that withdrawal from chronic nicotine decreased the expression of Erbb4 mRNA in the hippocampus of the adult mice but increased the expression of cytosolic Erbb4 protein in adolescent mice. Nrg3 mRNA and protein expression was not altered by chronic nicotine or withdrawal in the adult or adolescent cohorts, but Nrg3 mRNA and synaptosomal protein expression was lower in the adult withdrawal group when compared with their adolescent counterparts. These results highlight the age‐specific effects of nicotine withdrawal on the NSP and may contribute to the lower quit rate and higher cigarette consumption of smokers who initiation during adolescences. [ABSTRACT FROM AUTHOR]
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- 2022
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5. The Population-level Effect of Adjuvant Therapies on Breast Cancer Recurrence: Application of the Trend-in-Trend Design.
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Collin LJ, Waller LA, Cronin-Fenton DP, Ahern TP, Goodman M, McCullough LE, Kjærsgaard A, Woolpert KM, Silliman RA, Christiansen PM, Ejlertsen B, Toft Sørensen H, and Lash TL
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- Humans, Female, Middle Aged, Chemotherapy, Adjuvant, Adult, Receptors, Estrogen, Denmark epidemiology, Pharmacoepidemiology, Aged, Antineoplastic Agents, Hormonal therapeutic use, Premenopause, Receptor, ErbB-2, Postmenopause, Breast Neoplasms drug therapy, Tamoxifen therapeutic use, Neoplasm Recurrence, Local epidemiology, Trastuzumab therapeutic use
- Abstract
Purpose: Breast cancer has an average 10-year relative survival reaching 84%. This favorable survival is due, in part, to the introduction of biomarker-guided therapies. We estimated the population-level effect of the introduction of two adjuvant therapies-tamoxifen and trastuzumab-on recurrence using the trend-in-trend pharmacoepidemiologic study design., Methods: We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007., Results: For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4)., Conclusions: We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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6. Clinical best practices in interdisciplinary management of human epidermal growth factor receptor 2 antibody-drug conjugates-induced interstitial lung disease/pneumonitis: An expert consensus in China.
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Xu C, Chen Z, Xia Y, Shi Y, Fu P, Chen Y, Wang X, Zhang L, Li H, Chen W, Fu J, Huang L, Shu J, Wang O, Wu W, Xie B, Wang T, Zhang W, Shen S, Li Q, Luo T, Zhang B, Xie Y, Wang H, Wang Q, Wang W, Li Z, Song Z, Fang W, Zhong W, Zhang Y, Zhan P, Liu H, Lv T, Miao L, Min L, Wang F, Meng R, Zhu Y, Wang L, Wan B, Wang D, Hao Y, Zhou J, Huang L, Zhang Z, Lv D, Fang M, Lu Y, Si L, Song Y, and Wang X
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- Humans, China, Pneumonia drug therapy, Female, Consensus, Trastuzumab therapeutic use, Trastuzumab adverse effects, Breast Neoplasms drug therapy, Camptothecin analogs & derivatives, Receptor, ErbB-2, Lung Diseases, Interstitial drug therapy, Lung Diseases, Interstitial chemically induced, Immunoconjugates therapeutic use, Immunoconjugates adverse effects
- Abstract
Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice., (© 2024 American Cancer Society.)
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- 2024
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7. Treatment strategy for HER2-negative advanced gastric cancer: salvage-line strategy for advanced gastric cancer.
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Nishida N, Sakai D, and Satoh T
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- Humans, Immune Checkpoint Inhibitors therapeutic use, Ramucirumab, Angiogenesis Inhibitors therapeutic use, Progression-Free Survival, Vascular Endothelial Growth Factor A antagonists & inhibitors, Vascular Endothelial Growth Factor A metabolism, Stomach Neoplasms drug therapy, Stomach Neoplasms pathology, Receptor, ErbB-2, Salvage Therapy methods, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
After immune checkpoint inhibitor (ICI) comes into third-line treatment of advanced gastric cancer, the therapeutic strategy has been dramatically changed. Recent first-line regimen, which consists of ICI and chemotherapeutic agents, prolonged progression-free survival, and subsequent treatment options enabled continuous treatment beyond second-line therapy. Moreover, the advent of vascular endothelial growth factor (VEGF)-targeted agents including angiogenesis inhibitors and TKIs provides an opportunity of considering the interaction between ICI and anti-VEGF agents, and facilitating novel treatment proposal. Although clinical benefit of prolonged VEGF blockade after disease progression has not been confirmed in gastric cancer, combination therapy of cytotoxic agents and anti-VEGF agent, such as irinotecan plus ramucirumab demonstrated favorable objective response rate and progression-free survival in third- or later-line setting. In this review, we discuss recent progress and future directions of later-line treatments of HER2-negative advancer gastric cancer., (© 2024. The Author(s).)
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- 2024
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8. The role of the size of affinity ligands in the detection and characterization of extracellular vesicles.
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Pham CV, Chowdhury R, Patel S, Melke H, Hou Y, Xu H, Jia L, Duan A, Duan W, and Xiang D
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- Humans, Ligands, Cell Line, Tumor, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal immunology, Extracellular Vesicles chemistry, Receptor, ErbB-2, Biosensing Techniques methods
- Abstract
Surface proteins on the membrane of nano-sized extracellular vesicles (EVs) not only play crucial roles in cell-to-cell communication, but also are specific binding targets for EV detection, isolation and tracking. The low abundance of protein biomarkers on EV surface, the formation of clusters and the complex EV surface network impose significant challenges to the study of EVs. Employing bulky sized affinity ligands, such as antibodies, in the detection and characterization of these vesicles often result in reduced sensitivity of detection or poor quantification of proteins on the EV surface. By virtue of their small size and high specificity, Affibody molecules emerge as a potential alternative to their monoclonal antibody counterparts as robust affinity ligands in EV research. In this study, we present a theoretical framework on the superiority of anti-HER2 Affibodies over anti-HER2 antibodies in labeling and detecting HER2-positive EVs, followed by the demonstration of the advantages of HER2 Affibodies in accessing EV surface and the detection of EVs through multiple types of approaches including fluorescence intensity, colorimetry, and fluorescence polarization. HER2 Affibodies outperformed by 10-fold over three HER2 antibody clones in accessing HER2-positive EVs derived from different human cancer cell lines. Furthermore, HRP-Affibody molecules could detect EVs from cancer cells spiked into human serum with at least a 2-fold higher sensitivity compared with that of their antibody counterparts. In addition, in fluorescence polarization assays in which no separation of free from bound ligand is required, FITC-labeled HER2 Affibodies could sensitively detect HER2-positive EVs with a clinically relevant limit of detection, whilst HER2 antibodies failed to detect EVs in the same conditions. With the demonstrated superiority in accessing and detecting surface targets over bulky-sized antibodies in EVs, Affibodies may become the next-generation of affinity ligands in the precise characterization and quantification of molecular architecture on the surface of EVs., Competing Interests: Declaration of competing interest We declare that there are no financial and personal relationships with other people or organizations that could inappropriately influence (bias) our work described in this mansucript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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9. Deep learning-assisted monitoring of trastuzumab efficacy in HER2-Overexpressing breast cancer via SERS immunoassays of tumor-derived urinary exosomal biomarkers.
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Kim J, Son HY, Lee S, Rho HW, Kim R, Jeong H, Park C, Mun B, Moon Y, Jeong E, Lim EK, and Haam S
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- Animals, Female, Mice, Humans, Immunoassay methods, Antineoplastic Agents, Immunological therapeutic use, Trastuzumab therapeutic use, Exosomes chemistry, Receptor, ErbB-2, Breast Neoplasms drug therapy, Breast Neoplasms urine, Spectrum Analysis, Raman methods, Deep Learning, Biomarkers, Tumor urine, Biosensing Techniques
- Abstract
Monitoring drug efficacy is significant in the current concept of companion diagnostics in metastatic breast cancer. Trastuzumab, a drug targeting human epidermal growth factor receptor 2 (HER2), is an effective treatment for metastatic breast cancer. However, some patients develop resistance to this therapy; therefore, monitoring its efficacy is essential. Here, we describe a deep learning-assisted monitoring of trastuzumab efficacy based on a surface-enhanced Raman spectroscopy (SERS) immunoassay against HER2-overexpressing mouse urinary exosomes. Individual Raman reporters bearing the desired SERS tag and exosome capture substrate were prepared for the SERS immunoassay; SERS tag signals were collected to prepare deep learning training data. Using this deep learning algorithm, various complicated mixtures of SERS tags were successfully quantified and classified. Exosomal antigen levels of five types of cell-derived exosomes were determined using SERS-deep learning analysis and compared with those obtained via quantitative reverse transcription polymerase chain reaction and western blot analysis. Finally, drug efficacy was monitored via SERS-deep learning analysis using urinary exosomes from trastuzumab-treated mice. Use of this monitoring system should allow proactive responses to any treatment-resistant issues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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10. Optimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance.
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Chen M, Huang R, Chen R, Pan F, Shen X, Li H, Rong Q, An X, Xue C, and Shi Y
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- Humans, Female, Middle Aged, Retrospective Studies, Aged, Adult, Receptor, ErbB-2, Trastuzumab therapeutic use, Trastuzumab pharmacology, Trastuzumab administration & dosage, Neoplasm Metastasis, Progression-Free Survival, Aged, 80 and over, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Immunoconjugates therapeutic use, Immunoconjugates pharmacology, Drug Resistance, Neoplasm drug effects
- Abstract
Background: The optimal sequential strategy for antibody-drug conjugates (ADCs) in breast cancer remains uncertain. This study aimed to evaluate the efficacy and potential resistance of second ADC (ADC2) following the first ADC (ADC1) in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low MBC., Methods: This retrospective, multicenter, real-world study enrolled patients with MBC who received at least 2 different types of ADCs in 3 hospitals in China between July 1, 2017 and May 1, 2023. Outcomes included the objective response rate (ORR) for ADC1 and ADC2, progression free survival 2 (PFS2), defined as the time from initiation of ADC2 to progression, and overall survival (OS)., Results: Seventy-nine female patients were included, 64 of whom had HER2-positive disease. The ORR for ADC2 with similar payload of ADC1 was found to be 5.3%. When switching to a different payload, the ORR of ADC2 increased to 22.6%. The PFS2 for ADC2 remained similar regardless of whether the payload was similar or different. Switching to different payload showed a higher ORR in patients with rapid progression and a durable response longer than 6 months (41.2% vs 15.0%). Specifically, significantly longer PFS2 and OS were seen in patients treated with trastuzumab deruxtecan (T-Dxd) compared to those treated with disitamab vedotin (RC48) after progression from trastuzumab emtansine (T-DM1; median PFS2 5.37 months vs 3.30 months, HR = 0.40, 95% CI 0.17-0.93, P = .034; median OS 50.6 months vs 20.2 months, HR = 0.27, 95% CI 0.08-0.91, P = .034). For patients who progressed after T-Dxd, the median PFS2 was 6.05 months for those treated with RC48 versus 0.93 months for those treated with T-DM1 (HR = 0.03, 95% CI 0.002-0.353, P = .0093). Genomic analysis revealed that alternation of retinoblastoma1 was significantly associated with superior PFS., Conclusion: The alternation of payload achieves different responses in different settings. T-Dxd followed by RC48 may be a potentially beneficial strategy in HER2-positive disease. Further research is needed to elucidate the mechanism of cross-resistance., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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11. The Omission of Anthracycline Chemotherapy in Women with Early HER2-Negative Breast Cancer-A Systematic Review and Meta-Analysis.
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Giffoni de Mello Morais Mata D, Rush MB, Smith-Uffen M, Younus J, Lohmann AE, Trudeau M, and Morgan RL
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- Humans, Female, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Taxoids therapeutic use, Docetaxel therapeutic use, Breast Neoplasms drug therapy, Anthracyclines therapeutic use
- Abstract
Background: Anthracycline-taxane is the standard chemotherapy strategy for treating high-risk early breast cancer despite the potentially life-threatening adverse events caused by anthracyclines. Commonly, the combination of docetaxel and cyclophosphamide (TC) is considered an alternative option. However, the efficacy of TC compared to anthracycline-taxane chemotherapy is unclear. This study compares disease-free survival (DFS), overall survival (OS) and cardiotoxicity between adjuvant TC and anthracycline-taxane for stages I-III, HER2-negative breast cancer., Methods: A systematic search on MEDLINE, Embase and Cochrane CENTRAL for randomized-controlled trials published until 11 March 2024, yielded 203 studies with 11,803 patients, and seven trials were included., Results: TC results in little to no difference in DFS (HR 1.09, 95% CI 0.98-1.20; moderate-certainty of evidence); OS (1.02, 95% CI 0.89-1.16; high-certainty of evidence); and cardiotoxicity (RR 0.54, 95% CI 0.16-1.76; high-certainty of evidence), compared to anthracycline-taxane. In the subgroup analysis, patients with ≥4 lymph nodes had improved DFS from anthracycline-taxane over TC., Conclusions: Overall, there was no difference between TC and anthracycline-taxane in DFS, OS and cardiotoxicity. In women with ≥4 nodes, anthracycline-taxane was associated with a substantial reduction in relapse events, compared to TC. Our study supports the current standard of practice, which is to use anthracycline-taxane and TC chemotherapy as a reasonable option in select cases.
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- 2024
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12. Carcinoma en Cuirasse as the heralding sign of underlying HER-2 positive male breast cancer.
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Kapoor M, Sundriyal D, Sehrawat A, and Khanna M
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- Humans, Male, Adult, Receptor, ErbB-2, Lymphatic Metastasis, Diagnosis, Differential, Breast Neoplasms, Male diagnosis, Breast Neoplasms, Male diagnostic imaging, Breast Neoplasms, Male pathology, Skin Neoplasms diagnosis, Skin Neoplasms pathology
- Abstract
Carcinoma en cuirasse (CeC) is an uncommon presentation of metastatic cutaneous carcinoma, most often originating from breast carcinoma. We present a case study of a man in his 30s exhibiting progressive skin thickening over the left chest, alongside appetite and weight loss. On examination, the patient had painless skin induration and palpable, matted, hard, immobile and non-tender axillary, cervical and inguinal lymphadenopathy. Imaging revealed metabolically active left cervical, retro pectoral, inguinal and bilateral axillary lymph nodes with muscle involvement, likely neoplastic. Histopathology demonstrated metastatic carcinoma, morphologically originating from the breast. CeC most often presents after therapy, but our case reveals that it may be a presenting sign of an occult malignancy. CeC should be differentiated from non-oncological causes of skin thickening. Detailed history, physical examination and appropriate radiological investigations are essential. Although rare in young individuals, neoplastic aetiology should be considered if the history and physical examination suggest it., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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13. Biomarker-oriented chemo-immunotherapy for advanced gastric cancer.
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Kono K, Nakajima S, and Mimura K
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- Humans, Molecular Targeted Therapy, Claudins, Stomach Neoplasms drug therapy, Stomach Neoplasms therapy, Stomach Neoplasms pathology, Biomarkers, Tumor, Immunotherapy methods, B7-H1 Antigen antagonists & inhibitors, Receptor, ErbB-2
- Abstract
The biomarker-oriented chemo-immunotherapy is useful and promising in the development of new anticancer agents, since the responders can be enriched by selecting patients with biomarkers. Compared to colorectal and lung cancers, the development of biomarker-driven molecular-targeted therapeutics for gastric cancers has been straggled. However, several new biomarkers in gastric cancers have been discovered and clinical trials in enrichment design with certain biomarkers have been conducted. Therefore, there are currently several treatment options to treat gastric cancer patients based on individual biomarker-oriented strategies. In the present review, we describe the useful biomarkers in gastric cancer, with focusing on HER2, PD-L1, and Claudin18.2, in relation to their clinical significance and associated targeted agents., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
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- 2024
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14. Clinicopathologic characteristics of HER2-positive pure mucinous carcinoma of the breast
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Yunjeong Jang, Hera Jung, Han-Na Kim, Youjeong Seo, Emad Alsharif, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Yeon Hee Park, Eun Yoon Cho, and Soo Youn Cho
- Subjects
breast neoplasms ,receptor, erbb-2 ,pure mucinous adenocarcinoma ,Pathology ,RB1-214 - Abstract
Background Pure mucinous carcinoma (PMC) is a rare type of breast cancer, estimated to represent 2% of invasive breast cancer. PMC is typically positive for estrogen receptors (ER) and progesterone receptors (PR) and negative for human epidermal growth factor receptor 2 (HER2). The clinicopathologic characteristics of HER2-positive PMC have not been investigated. Methods Pathology archives were searched for PMC diagnosed from January 1999 to April 2018. Clinicopathologic data and microscopic findings were reviewed and compared between HER2-positive PMC and HER2-negative PMC. We also analyzed the differences in disease-free survival (DFS) and overall survival according to clinicopathologic parameters including HER2 status in overall PMC cases. Results There were 21 HER2-positive cases (4.8%) in 438 PMCs. The average tumor size of HER2-positive PMC was 32.21 mm (± 26.55). Lymph node metastasis was present in seven cases. Compared to HER2-negative PMC, HER2-positive PMC presented with a more advanced T category (p < .001), more frequent lymph node metastasis (p = .009), and a higher nuclear and histologic grade (p < .001). Microscopically, signet ring cells were frequently observed in HER2-positive PMC (p < .001), whereas a micropapillary pattern was more frequent in HER2-negative PMC (p = .012). HER2-positive PMC was more frequently negative for ER (33.3% vs. 1.2%) and PR (28.6% vs. 7.2%) than HER2-negative PMC and showed a high Ki-67 labeling index. During follow-up, distant metastasis and recurrence developed in three HER2-positive PMC patients. Multivariate analysis revealed that only HER2-positivity and lymph node status were significantly associated with DFS. Conclusions Our results suggest that HER2-positive PMC is a more aggressive subgroup of PMC. HER2 positivity should be considered for adequate management of PMC.
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- 2020
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15. Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial.
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Hegde M, Navai S, DeRenzo C, Joseph SK, Sanber K, Wu M, Gad AZ, Janeway KA, Campbell M, Mullikin D, Nawas Z, Robertson C, Mathew PR, Zhang H, Mehta B, Bhat RR, Major A, Shree A, Gerken C, Kalra M, Chakraborty R, Thakkar SG, Dakhova O, Salsman VS, Grilley B, Lapteva N, Gee A, Dotti G, Bao R, Salem AH, Wang T, Brenner MK, Heslop HE, Wels WS, Hicks MJ, Gottschalk S, and Ahmed N
- Subjects
- Humans, Middle Aged, Female, Male, Adult, Aged, T-Lymphocytes immunology, Lymphocyte Depletion methods, Prospective Studies, Vidarabine analogs & derivatives, Vidarabine administration & dosage, Vidarabine therapeutic use, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Treatment Outcome, Sarcoma therapy, Sarcoma immunology, Receptor, ErbB-2, Immunotherapy, Adoptive methods, Immunotherapy, Adoptive adverse effects, Receptors, Chimeric Antigen immunology
- Abstract
In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 10
8 T cells per m2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 108 CAR+ T cells per m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)- Published
- 2024
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16. A multicentric study of radiomics and artificial intelligence analysis on contrast-enhanced mammography to identify different histotypes of breast cancer.
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Petrillo A, Fusco R, Petrosino T, Vallone P, Granata V, Rubulotta MR, Pariante P, Raiano N, Scognamiglio G, Fanizzi A, Massafra R, Lafranceschina M, La Forgia D, Greco L, Ferranti FR, De Soccio V, Vidiri A, Botta F, Dominelli V, Cassano E, Sorgente E, Pecori B, Cerciello V, and Boldrini L
- Subjects
- Humans, Female, Middle Aged, Aged, Italy, Adult, Neoplasm Grading, Radiographic Image Interpretation, Computer-Assisted methods, Receptor, ErbB-2, Sensitivity and Specificity, Radiomics, Breast Neoplasms diagnostic imaging, Breast Neoplasms pathology, Contrast Media, Artificial Intelligence, Mammography methods
- Abstract
Objective: To evaluate the performance of radiomic analysis on contrast-enhanced mammography images to identify different histotypes of breast cancer mainly in order to predict grading, to identify hormone receptors, to discriminate human epidermal growth factor receptor 2 (HER2) and to identify luminal histotype of the breast cancer., Methods: From four Italian centers were recruited 180 malignant lesions and 68 benign lesions. However, only the malignant lesions were considered for the analysis. All patients underwent contrast-enhanced mammography in cranium caudal (CC) and medium lateral oblique (MLO) view. Considering histological findings as the ground truth, four outcomes were considered: (1) G1 + G2 vs. G3; (2) HER2 + vs. HER2 - ; (3) HR + vs. HR - ; and (4) non-luminal vs. luminal A or HR + /HER2- and luminal B or HR + /HER2 + . For multivariate analysis feature selection, balancing techniques and patter recognition approaches were considered., Results: The univariate findings showed that the diagnostic performance is low for each outcome, while the results of the multivariate analysis showed that better performances can be obtained. In the HER2 + detection, the best performance (73% of accuracy and AUC = 0.77) was obtained using a linear regression model (LRM) with 12 features extracted by MLO view. In the HR + detection, the best performance (77% of accuracy and AUC = 0.80) was obtained using a LRM with 14 features extracted by MLO view. In grading classification, the best performance was obtained by a decision tree trained with three predictors extracted by MLO view reaching an accuracy of 82% on validation set. In the luminal versus non-luminal histotype classification, the best performance was obtained by a bagged tree trained with 15 predictors extracted by CC view reaching an accuracy of 94% on validation set., Conclusions: The results suggest that radiomics analysis can be effectively applied to design a tool to support physician decision making in breast cancer classification. In particular, the classification of luminal versus non-luminal histotypes can be performed with high accuracy., (© 2024. Italian Society of Medical Radiology.)
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- 2024
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17. [Trastuzumab-deruxtecan monotherapy in HER2-activated advanced non-small cell lung cancer pre-treated with platinum-based chemotherapy with or without immunotherapy].
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Rivier C and Lavaud P
- Subjects
- Humans, Antineoplastic Agents, Immunological therapeutic use, Immunoconjugates therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Female, Immunotherapy methods, Antibodies, Monoclonal, Humanized therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Trastuzumab therapeutic use, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Receptor, ErbB-2, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Camptothecin administration & dosage
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- 2024
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18. A real-world study of treatment sequences and second-line clinical outcomes in patients with HER2-positive metastatic breast cancer in US community practice.
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Varghese D, Cruz GI, Johanson C, Toland L, Miranda M, Faherty EC, Harland D, and Kaplan HG
- Subjects
- Humans, Female, Middle Aged, Aged, United States, Antibodies, Monoclonal, Humanized therapeutic use, Retrospective Studies, Neoplasm Metastasis, Progression-Free Survival, Treatment Outcome, Camptothecin analogs & derivatives, Immunoconjugates, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Receptor, ErbB-2, Trastuzumab therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Ado-Trastuzumab Emtansine therapeutic use
- Abstract
Purpose: Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US)., Methods: HER2 + mBC patients initiating 2L treatment (index date) between January 2014 and February 2021 were identified from the Syapse Learning Health Network (LHN) database. Summary statistics for patient characteristics, treatment received, reasons for 2L discontinuation and time to 2L-clinical outcomes are reported., Results: Of the 312 patients initiating 2L treatment, had a median age of 59 years (interquartile range [IQR], 50-66) at the start of 2L. The majority were white (69%) and had de novo mBC (62%). Top three 2L regimens included T-DM1 ± endocrine therapy (29%), trastuzumab/pertuzumab/taxane (10%) and T-DM1/trastuzumab (8%). Around 88% discontinued 2L and 63% received subsequent treatment. Median time-to-next-treatment was 10.6 months (95% CI, 8.8-13.3) and real-world progression-free-survival was 7.9 months (95% CI, 7.0-9.9). Among 274 patients who discontinued 2L, 47% discontinued due to progression and 17% because of intolerance/toxicity, respectively., Conclusion: This real-world US study showed that approximately two-thirds of 2L patients received subsequent therapy and disease progression was the most common reason for 2L discontinuation highlighting the need for timely 2L treatment with the most efficacious drug to allow patients to achieve longer treatment duration and delayed progression., (© 2024. The Author(s).)
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- 2024
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19. Breast cancer in northern Peru: molecular subtypes and HER2 low.
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Gómez-Rázuri K, Abad-Licham M, Astigueta J, and Moreno J
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- Humans, Peru, Female, Cross-Sectional Studies, Middle Aged, Adult, Aged, Aged, 80 and over, Young Adult, Receptor, ErbB-2, Breast Neoplasms classification, Breast Neoplasms genetics, Breast Neoplasms pathology
- Abstract
This study aimed to understand the immunohistochemical profile of breast cancer and to identify the HER2 low subgroup in the northern macro-region of Peru. A cross-sectional study was conducted in 1176 patients from the Regional Institute of Neoplastic Diseases Northern Peru, from January 2016 to December 2023. We analyzed the data (age, histological type, grade and complementary results), with frequencies and percentages. The profile corresponded to: luminal B (45.6%); luminal A (24.7%); triple negative (18.2%); and HER2 positive non luminal (11.5%). In addition, 215 patients presented HER2 low (25.1% of those previously considered negative). This study provides evidence that the subtyping of breast cancer has changed, being luminal B the most frequent. It is essential to involve health policies to acquire targeted therapies considering HER2 low patients. Motivation for the study. Molecular classification of breast cancer allows the use of targeted treatments. Information on this profile in the northern macroregion of Peru is unknown. In addition, new therapies have appeared for a subgroup of patients. Main findings. In this study, the most frequent molecular subtypes were: luminal B, luminal A, triple negative and non-luminal HER2. Also, 18.3% of patients had low HER2 expression. Implications. Health policies should be aligned with scientific advances, to guarantee targeted therapies and to update the information in health manuals or protocols.
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- 2024
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20. Trastuzumab-emtansine versus other anti-HER2 regimens in early or unresectable or metastatic HER-2 positive breast cancer: systematic review and network meta-analysis.
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Ciapponi A, Bardach A, Colaci C, Rodríguez Cairoli F, Argento F, Korbenfeld E, and García Martí S
- Subjects
- Humans, Female, Trastuzumab therapeutic use, Network Meta-Analysis, Randomized Controlled Trials as Topic, Neoplasm Metastasis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Maytansine analogs & derivatives, Maytansine therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Ado-Trastuzumab Emtansine therapeutic use, Receptor, ErbB-2, Antineoplastic Agents, Immunological therapeutic use
- Abstract
Objective.: Motivation for the study. Treatment options for HER2-positive breast cancer were evaluated, focusing on the efficacy and safety of trastuzumab-emtansine (T-DM1) compared to other anti-HER2 therapies. Main findings. Trastuzumab-deruxtecan (T-DXd) and PyroCap emerged as promising alternatives, showing substantial improvements in progression-free survival for locally advanced or metastatic breast cancer. T-DM1 showed superior efficacy to the other treatments. Implications. Our findings could inform healthcare decision-making processes to optimize strategies for HER2-positive breast cancer, and potentially improve health outcomes and quality of life. We aimed to study the efficacy and safety of trastuzumab-emtansine (T-DM1) versus other anti-HER2 therapies in HER2+ breast cancer (BC)., Materials and Methods.: We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs). Our study focused on patients undergoing treatment for unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (mBC), which included regimens involving trastuzumab and taxanes. Additionally, we considered cases within the first 6 months of treatment for HER2+ early breast cancer (EBC)., Results.: A total of 23 RCTs and 41 reports were included in our analysis. LABC and mBC showed no statistically significant difference in any of the comparisons of T-DM1 versus the other anti-HER2+ therapies. When assessing progression-free survival (PFS), trastuzumab-deruxtecan (T-DXd) and PyroCap demonstrated greater efficacy compared to other treatments (Hazard Ratio [HR]: 3.57; 95% confidence interval [CI]: 2.75-4.63 and HR: 1.82; 95% CI: 1.35-2.44; respectively), while T-DM1 alone exhibited superior effectiveness compared to LapCap (HR: 0.65; 95% CI: 0.55-0.77), TrasCap (HR: 0.65; 95% CI: 0.46-0.91), LapCapCitu (HR: 0.60; 95% CI: 0.33-1.10), Nera (HR: 0.55; 95% CI: 0.39-0.77), and Cap (HR: 0.37; 95% CI: 0.28-0.49)., Conclusions.: NMA allows a ranking based on the comparative efficacy and safety among the interventions available. Although superior to other schemes, T-DM1 showed a lower efficacy performance in PFS and overall response rate and a trend towards worse overall survival than T-DXd.
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- 2024
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21. Greatly isolated heterogeneous circulating tumor cells using hybrid engineered cell membrane-camouflaged magnetic nanoparticles.
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Jiang X, Zhang X, Guo C, Liu Z, Guo X, Tian Z, Wang Z, Yang J, Huang X, and Ou L
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- Humans, Cell Line, Tumor, Receptor, ErbB-2, Epithelial Cell Adhesion Molecule metabolism, ErbB Receptors genetics, ErbB Receptors metabolism, Neoplasms, Neoplastic Cells, Circulating pathology, Neoplastic Cells, Circulating metabolism, Magnetite Nanoparticles chemistry, Cell Separation methods, Cell Membrane metabolism, Cell Membrane chemistry, Biomarkers, Tumor blood
- Abstract
Background: Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation., Methods: To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis., Conclusions: This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis., (© 2024. The Author(s).)
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- 2024
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22. Prognostic stratification ability of the CPS+EG scoring system in HER2-low and HER2-zero early breast cancer treated with neoadjuvant chemotherapy.
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Roussot N, Constantin G, Desmoulins I, Bergeron A, Arnould L, Beltjens F, Mayeur D, Kaderbhai C, Hennequin A, Jankowski C, Padeano MM, Costaz H, Jacinto S, Michel E, Amet A, Coutant C, Costa B, Jouannaud C, Deblock M, Levy C, Ferrero JM, Kerbrat P, Brain E, Mouret-Reynier MA, Coudert B, Bertaut A, and Ladoire S
- Subjects
- Humans, Female, Prognosis, Neoadjuvant Therapy methods, Retrospective Studies, Neoplasm Staging, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemotherapy, Adjuvant, Disease-Free Survival, Breast Neoplasms pathology
- Abstract
Background: The CPS+EG scoring system was initially described in unselected early breast cancer (eBC) patients treated with neoadjuvant chemotherapy (NAC), leading to refined prognostic stratification, and thus helping to select patients for additional post-NAC treatments. It remains unknown whether the performance is the same in new biological breast cancer entities such as the HER2-low subtype., Patients and Methods: Outcomes (disease-free (DFS) and overall survival OS)) of 608 patients with HER2-non amplified eBC and treated with NAC were retrospectively analyzed according to CPS-EG score. We compared the prognostic stratification abilities of the CPS+EG in HER2-low and HER2-0 eBC, analyzing ER+ and ER- tumors separately., Results: In ER+ eBC, the CPS+EG scoring system seems to retain a prognostic value, both in HER2-low and HER2-0 tumors, by distinguishing populations with significantly different outcomes (good: score 0-1, poor: score 2-3, and very poor: score 4-5). Using C-indices for DFS and OS, CPS+EG provided the highest prognostic information in ER+ eBC, especially in HER2-0 tumors. In contrast, in ER- eBC, the CPS+EG does not appear to be able to distinguish different outcome groups, either in HER2-low or HER2-0 tumors. In ER- eBC, C-indices for DFS and OS were highest for pathological stage, reflecting the predominant prognostic importance of residual disease in this subtype., Conclusions: HER2-low status does not influence the prognostic performance of the CPS+EG score. Our results confirm the usefulness of the CPS+EG score in stratifying the prognosis of ER+ eBC after NAC, for both HER2-0 and HER2-low tumors. For ER- eBC, HER2-low status does not influence the performance of the CPS+EG score, which was lower than that of the pathological stage alone., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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23. Disease-free survival as a surrogate for overall survival in HR+/HER2- early breast cancer: A correlation analysis.
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Untch M, Pérol D, Mayer EL, Cortes J, Nusch A, Cameron D, Barrios C, Delea T, Danyliv A, Mishra N, Gupta R, Pathak P, and Fasching PA
- Subjects
- Adult, Humans, Female, Disease-Free Survival, Progression-Free Survival, Proportional Hazards Models, Chemotherapy, Adjuvant, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy
- Abstract
Background: Overall survival (OS) is a universally accepted measure of clinical benefit; however, prolonged follow-up is needed to observe sufficient events. Disease-free survival (DFS) has been widely adopted as a primary endpoint for early breast cancer (EBC) trials, as follow-up is comparatively shorter. Here, we present an analysis evaluating DFS as a surrogate for OS for adjuvant treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) EBC., Methods: A systematic literature review which included randomized controlled trials (RCTs) with ≥80% of adult patients with HR+/HER2- EBC was conducted. The RCTs evaluated various systemic therapeutic categories; key inclusion criteria included reporting of DFS and OS hazard ratios (HRs) and mature OS data. Spearman rank correlation and weighted linear regression analyses evaluated DFS and OS HR correlation. A scenario analysis tested base-case analysis robustness, and a parallel analysis using patient-level data was conducted., Results: The base case (N = 14 RCTs) showed an unweighted Spearman coefficient of 0.81 between OS and DFS (weighted: 0.81), with 84% of the variability in OS explained by DFS differences (R
2 from weighted regression). The surrogate threshold effect (Burzykowski T, Buyse M. Pharm Stat. 2006;5:173-186) was 0.82 for DFS/OS HR. Scenario analysis (n = 9 RCTs), which excluded chemotherapy trials, and patient-level analysis using FACE trial data were consistent with the base-case analysis., Conclusions: These analyses support DFS as a reliable surrogate endpoint for OS in adjuvant HR+/HER2- EBC trials. Using DFS as a surrogate measure will permit timelier access to novel treatments for patients with HR+/HER2- EBC., Competing Interests: Declaration of Competing Interest Representatives of the sponsor were responsible for trial design, data compilation, and confirming the accuracy of the analyses. All authors had access to the data and vouch for the completeness and accuracy of the data as well as the fidelity of the trial to the protocol. All authors participated in the writing and review of all manuscript drafts and contributed to the interpretation of the data. Medical writing support and editorial support were paid for by Novartis., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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24. ASO Author Reflections: Neoadjuvant Systemic Therapy and Nodal Management in cT1-2 N0 Triple-Negative Breast Cancer.
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Cortina CS, Rogers CC, and Teshome M
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- Humans, Female, Neoadjuvant Therapy, Sentinel Lymph Node Biopsy, Receptor, ErbB-2, Axilla, Triple Negative Breast Neoplasms drug therapy, Breast Neoplasms drug therapy
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- 2024
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25. Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).
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Tokunaga M, Machida N, Mizusawa J, Ito S, Yabusaki H, Hirao M, Watanabe M, Imamura H, Kinoshita T, Yasuda T, Hihara J, Fukuda H, Yoshikawa T, Boku N, and Terashima M
- Subjects
- Humans, Trastuzumab therapeutic use, Lymphatic Metastasis pathology, Japan, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Esophagogastric Junction pathology, Medical Oncology, Neoadjuvant Therapy, Stomach Neoplasms drug therapy, Stomach Neoplasms surgery, Stomach Neoplasms pathology, Adenocarcinoma drug therapy, Adenocarcinoma surgery, Adenocarcinoma pathology, Esophageal Neoplasms
- Abstract
Background: This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis., Methods: Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006., Results: This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively., Conclusions: Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)
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- 2024
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26. Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With BRAF, ERBB2/HER2, MET , or RET Alterations: A Systematic Literature Review.
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Akers KG, Oskar S, Zhao B, Frederickson AM, and Arunachalam A
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- Humans, Immune Checkpoint Inhibitors therapeutic use, Proto-Oncogene Proteins B-raf genetics, B7-H1 Antigen metabolism, Programmed Cell Death 1 Receptor, Proto-Oncogene Proteins c-ret genetics, Proto-Oncogene Proteins c-ret therapeutic use, Receptor, ErbB-2, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood. A systematic literature review was performed to summarize evidence from clinical trials and observational studies on objective response rate, progression-free survival, and overall survival in patients whose tumors express these biomarkers and who were treated with PD-1/PD-L1 inhibitors. Searches of Embase, MEDLINE, conference abstracts, and a clinical trial registry identified a total of 12 unique studies: 4 studies included patients with BRAF V600E mutation, 6 studies included patients with HER2/ERBB2 alteration, 7 studies included patients with MET exon 14 skipping mutation, and 5 studies included patients with RET rearrangement. Across studies, there was heterogeneity in treatment and patient characteristics and a lack of reporting on many important predictive and prognostic factors, including treatment regimens, patients' line of therapy, and tumor PD-L1 expression, which may explain the wide variation in objective response rate, progression-free survival, and overall survival across studies. Therefore, additional studies prospectively evaluating clinical outcomes of PD-1/PD-L1 inhibitors among patients with advanced or metastatic NSCLC whose tumors harbor emerging predictive or prognostic biomarkers are needed to determine whether this class of immunotherapy can provide additional survival benefits for these patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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27. Survival outcomes in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy: a meta-analysis.
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Xia LY, Cao XC, and Yu Y
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- Humans, Female, Neoadjuvant Therapy, Receptor, ErbB-2, Disease-Free Survival, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemotherapy, Adjuvant, Breast Neoplasms pathology
- Abstract
Background: The survival outcomes in HER2-low versus HER2-zero breast cancer (BC) after neoadjuvant chemotherapy (NACT) remain unclear. The meta-analysis was conducted to summarize current evidence about the survival outcomes in HER2-low versus HER2-zero BC., Methods: We conducted a systematic search in PubMed and EMBASE databases to identify relevant studies., Results: A total of 14 studies with 53,714 patients were included. Overall, 34,037 patients (63.37%) were HER2-low, and 19,677 patients (36.63%) were HER2-zero. Patients with HER2-low tumors had a significantly lower pathological complete response (pCR) rate than patients with HER2-zero tumors, regardless of the hormone receptor status. Compared with HER2-zero breast cancer, the overall survival (OS) and disease-free survival (DFS) of HER2-low BC were longer in the overall cohort (HR = 0.72; 95% CI = 0.61-0.85; P < 0.0001; HR = 0.83; 95% CI = 0.75-0.92; P = 0.0002); however, no differences were observed in terms of OS and DFS between HER2-low and HER2-zero BC in the HR-negative group. In the HR-positive group, HER2-low status had no significant impact on OS, while significantly associated with increased DFS (HR = 0.85; 95% CI = 0.76-0.96; P = 0.007)., Conclusion: These results suggest that although HER2-low BC has a poor response to NACT, it is correlated with favorable OS and DFS after NACT in the overall cohort as well as longer DFS in the HR-positive group., (© 2024. The Author(s).)
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- 2024
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28. Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials.
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Sheng X, Wang L, He Z, Shi Y, Luo H, Han W, Yao X, Shi B, Liu J, Hu C, Liu Z, Guo H, Yu G, Ji Z, Ying J, Ling Y, Yu S, Hu Y, Guo J, Fang J, Zhou A, and Guo J
- Subjects
- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Transitional Cell drug therapy, Urinary Bladder Neoplasms drug therapy, Neutropenia drug therapy, Antibodies, Monoclonal, Oligopeptides, Receptor, ErbB-2
- Abstract
Purpose: To evaluate the efficacy and safety of disitamab vedotin (DV, RC48-ADC), a novel humanized anti-human epidermal growth factor receptor 2 (HER2) antibody conjugated with monomethyl auristatin E, in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (UC) refractory to standard or regular therapies., Patients and Methods: The data analyzed and reported are from two phase II, open-label, multicenter, single-arm studies (RC48-C005 and RC48-C009) in patients with HER2-positive (immunohistochemistry 3+ or 2+) locally advanced or metastatic UC who have progressed on at least one previous line of systemic chemotherapy. Patients received DV treatment (2 mg/kg IV infusion, once every 2 weeks). The primary end point was objective response rate (ORR) assessed by a blinded independent review committee (BIRC). Progression-free survival (PFS), overall survival (OS), and safety were also assessed., Results: One hundred and seven patients were enrolled in total. The overall confirmed ORR by BIRC was 50.5% (95% CI, 40.6 to 60.3). Consistent results were observed in prespecified subgroups including patients with liver metastasis and patients previously treated with anti-PD-1/L1 therapies. By the cutoff date of May 10, 2022, the median duration of response was 7.3 months (95% CI, 5.7 to 10.8). The median PFS and OS were 5.9 months (95% CI, 4.3 to 7.2) and 14.2 months (95% CI, 9.7 to 18.8), respectively. The most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (68.2%), leukopenia (50.5%), AST increased (42.1%), and neutropenia (42.1%). Fifty-eight (54.2%) patients experienced grade ≥3 TRAEs, including peripheral sensory neuropathy (18.7%) and neutropenia (12.1%)., Conclusion: DV demonstrated a promising efficacy with a manageable safety profile in patients with HER2-positive locally advanced or metastatic UC who had progressed on at least one line of systemic chemotherapy.
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- 2024
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29. Breast cancer therapy in China: Introducing the Special Collection.
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Wang X and O'Regan RM
- Subjects
- Humans, Female, Receptor, ErbB-2, China epidemiology, Immunotherapy, Breast Neoplasms therapy, Triple Negative Breast Neoplasms therapy
- Published
- 2024
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30. Patient-Reported Outcomes in OlympiA: A Phase III, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib in g BRCA1/2 Mutations and High-Risk Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer.
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Ganz PA, Bandos H, Španić T, Friedman S, Müller V, Kuemmel S, Delaloge S, Brain E, Toi M, Yamauchi H, de Dueñas EM, Armstrong A, Im SA, Song CG, Zheng H, Sarosiek T, Sharma P, Geng C, Fu P, Rhiem K, Frauchiger-Heuer H, Wimberger P, t'Kint de Roodenbeke D, Liao N, Goodwin A, Chakiba-Brugère C, Friedlander M, Lee KS, Giacchetti S, Takano T, Henao-Carrasco F, Virani S, Valdes-Albini F, Domchek SM, Bane C, McCarron EC, Mita M, Rossi G, Rastogi P, Fielding A, Gelber RD, Scheepers ED, Cameron D, Garber J, Geyer CE, and Tutt ANJ
- Subjects
- Female, Humans, BRCA1 Protein genetics, BRCA2 Protein genetics, Fatigue chemically induced, Mutation, Nausea, Patient Reported Outcome Measures, Vomiting, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Phthalazines, Piperazines, Quality of Life, Receptor, ErbB-2
- Abstract
Purpose: The OlympiA randomized phase III trial compared 1 year of olaparib (OL) or placebo (PL) as adjuvant therapy in patients with germline BRCA1/2 , high-risk human epidermal growth factor receptor 2-negative early breast cancer after completing (neo)adjuvant chemotherapy ([N]ACT), surgery, and radiotherapy. The patient-reported outcome primary hypothesis was that OL-treated patients may experience greater fatigue during treatment., Methods: Data were collected before random assignment, and at 6, 12, 18, and 24 months. The primary end point was fatigue, measured with the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary end points, assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 item, included nausea and vomiting (NV), diarrhea, and multiple functional domains. Scores were compared between treatment groups using mixed model for repeated measures. Two-sided P values <.05 were statistically significant for the primary end point. All secondary end points were descriptive., Results: One thousand five hundred and thirty-eight patients (NACT: 746, ACT: 792) contributed to the analysis. Fatigue severity was statistically significantly greater for OL versus PL, but not clinically meaningfully different by prespecified criteria (≥3 points) at 6 months (diff OL v PL: NACT: -1.3 [95% CI, -2.4 to -0.2]; P = .022; ACT: -1.3 [95% CI, -2.3 to -0.2]; P = .017) and 12 months (NACT: -1.6 [95% CI, -2.8 to -0.3]; P = .017; ACT: -1.3 [95% CI, -2.4 to -0.2]; P = .025). There were no significant differences in fatigue severity between treatment groups at 18 and 24 months. NV severity was worse in patients treated with OL compared with PL at 6 months (NACT: 6.0 [95% CI, 4.1 to 8.0]; ACT: 5.3 [95% CI, 3.4 to 7.2]) and 12 months (NACT: 6.4 [95% CI, 4.4 to 8.3]; ACT: 4.5 [95% CI, 2.8 to 6.1]). During treatment, there were some clinically meaningful differences between groups for other symptoms but not for function subscales or global health status., Conclusion: Treatment-emergent symptoms from OL were limited, generally resolving after treatment ended. OL- and PL-treated patients had similar functional scores, slowly improving during the 24 months after (N)ACT and there was no clinically meaningful persistence of fatigue severity in OL-treated patients.
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- 2024
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31. Establishment of a Novel Cancer-Specific Anti-HER2 Monoclonal Antibody H 2 Mab-250/H 2 CasMab-2 for Breast Cancers.
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Kaneko MK, Suzuki H, and Kato Y
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- Humans, Female, Antibodies, Monoclonal, Trastuzumab, Receptor, ErbB-2, Cell Line, Tumor, Breast Neoplasms, Antineoplastic Agents
- Abstract
Overexpression of human epidermal growth factor receptor 2 (HER2) in breast and gastric cancers is an important target for monoclonal antibody (mAb) therapy. All therapeutic mAbs, including anti-HER2 mAbs, exhibit adverse effects probably due to the recognition of antigens expressed in normal cells. Therefore, tumor-selective or specific mAbs can be beneficial in reducing the adverse effects. In this study, we established a novel cancer-specific anti-HER2 monoclonal antibody, named H
2 Mab-250/H2 CasMab-2 (IgG1 , kappa). H2 Mab-250 reacted with HER2-positive breast cancer BT-474 and SK-BR-3 cells. Importantly, H2 Mab-250 did not react with nontransformed normal epithelial cells (HaCaT and MCF 10A) and immortalized normal epithelial cells in flow cytometry. In contrast, most anti-HER2 mAbs, such as H2 Mab-119 and trastuzumab reacted with both cancer and normal epithelial cells. Immunohistochemical analysis demonstrated that H2 Mab-250 possesses much higher reactivity to the HER2-positive breast cancer tissues compared with H2 Mab-119, and did not react with normal tissues, including heart, breast, stomach, lung, colon, kidney, and esophagus. The epitope mapping demonstrated that the Trp614 of HER2 domain IV mainly contributes to the recognition by H2 Mab-250. H2 Mab-250 could contribute to the development of chimeric antigen receptor-T or antibody-drug conjugates without adverse effects for breast cancer therapy.- Published
- 2024
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32. Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan.
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Heist RS, Sands J, Bardia A, Shimizu T, Lisberg A, Krop I, Yamamoto N, Kogawa T, Al-Hashimi S, Fung SSM, Galor A, Pisetzky F, Basak P, Lau C, and Meric-Bernstam F
- Subjects
- Humans, Female, Trastuzumab, Receptor, ErbB-2, Camptothecin, Clinical Trials, Phase I as Topic, Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms, Lung Neoplasms, Antineoplastic Agents, Immunoconjugates adverse effects, Breast Neoplasms
- Abstract
Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery of cytotoxic agents to tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2 (TROP2), a protein that is broadly expressed in several types of solid tumors. Dato-DXd is being investigated across multiple solid tumor indications. In the ongoing, first-in-human TROPION-PanTumor01 phase I study (ClinicalTrials.gov: NCT03401385), encouraging and durable antitumor activity and a manageable safety profile was demonstrated in patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor2-negative breast cancer (HR+/HER2- BC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC). Improved understanding of the adverse events (AEs) that are associated with Dato-DXd and their optimal management is essential to ensure safe and successful administration. Interstitial lung disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, and ocular surface events have been identified as AEs of special interest (AESIs) for which appropriate prevention, monitoring, and management is essential. This article summarizes the incidence of AESIs among patients with HR+/HER2- BC, TNBC, and NSCLC reported in TROPION-PanTumor01. We report our recommendations for AESI prophylaxis, early detection, and management, using experience gained from treating AESIs that occur with Dato-DXd in clinical trials., Competing Interests: Declaration of competing interest The authors have declared all competing financial interests or personal relationships that could have appeared to influence the work reported in this paper above., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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33. Model-informed dose selection for an investigational human epidermal growth factor receptor 2 antibody-drug conjugate FS-1502 in patients with human epidermal growth factor receptor 2-expressing advanced malignant solid tumours.
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Sun Y, Li C, Wang X, Zheng Y, Wu Z, Hui AM, and Diao L
- Subjects
- Humans, Receptor, ErbB-2, Antineoplastic Agents, Neoplasms drug therapy, Neoplasms chemically induced, Immunoconjugates adverse effects, Immunoconjugates pharmacokinetics
- Abstract
Aims: The dose-escalation phase (phase Ia study) of a novel human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) FS-1502 included a dose range from 0.1 to 3.5 mg/kg in HER2-expressing advanced malignant solid tumours. However, the defined maximum tolerated dose was not reached. This model-informed approach integrated population pharmacokinetic (PopPK) modelling and exposure-response (E-R) analysis to facilitate dose selection for phase II., Methods: The PopPK model was constructed using PK data from 109 Chinese patients who received doses of 0.1-3.5 mg/kg FS-1502 every 3 (Q3W) or 4 weeks during a phase I dose-escalation and dose expansion trial. The structural model consisted of compartment models for FS-1502 and unconjugated monomethyl auristatin F. E-R was explored for the percentage change in tumour size, overall response rate and treatment-related adverse events., Results: A semi-mechanistic 2-analyte PopPK model was developed. The FS-1502 PK data were best described by a 2-compartment PK model with parallel linear and nonlinear Michaelis-Menten eliminations. The PK of unconjugated monomethyl auristatin F was described by a 2-compartment model with first-order elimination. E-R analysis supported the clinically meaningful efficacy of FS-1502 at 2.3 mg/kg and above. However, 2.3 mg/kg Q3W was considered to have a better benefit-risk balance due to a lower incidence of safety events without a significant reduction in efficacy compared to 3.0 mg/kg Q3W., Conclusion: This PopPK and E-R analysis guided the recommended phase II dose selection of 2.3 mg/kg Q3W and supported body weight-based dosing for an investigational HER2 ADC FS-1502., (© 2023 British Pharmacological Society.)
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- 2024
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34. Is Pertuzumab Plus Trastuzumab Without Chemotherapy a Reasonable Treatment for ERBB2-Positive Metastatic Breast Cancer?
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Sun R and Wei LJ
- Subjects
- Humans, Female, Trastuzumab, Antibodies, Monoclonal, Humanized therapeutic use, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms pathology
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- 2024
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35. A Real-world Study of Everolimus Plus Aromatase Inhibitor in Hormone Receptor-positive, HER2-negative Advanced Breast Cancer.
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Ardavanis-Loukeris G, Kokkali S, Perdikari K, Karatrasoglou E, Talagani S, Tzovaras A, and Ardavanis A
- Subjects
- Humans, Female, Receptor, ErbB-2, Aromatase Inhibitors adverse effects, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols adverse effects, Androstadienes adverse effects, Everolimus adverse effects, Breast Neoplasms pathology
- Abstract
Background/aim: Everolimus in combination with exemestane was shown to offer benefit versus exemestane monotherapy in hormone receptor (HR)-positive, HER2-negative advanced breast cancer patients who progressed after aromatase inhibitor (AI) therapy., Patients and Methods: The medical records of metastatic breast cancer patients, treated with everolimus, were retrospectively reviewed to generate real life safety and efficacy data., Results: Sixty-eight percent of the patients had received chemotherapy (for early or metastatic disease) and 26% had received chemotherapy for metastatic disease. Among the 25 included patients, the most common adverse events were fatigue, neutropenia, epistaxis, stomatitis, and pneumonitis. Toxicity led to treatment discontinuation in 3 patients (12%). The median progression-free survival (PFS) was 7 months (95%CI=3.5-10.5). With a median follow-up of 73.3 months, the median overall survival was not reached. Twenty-five percent of the patients had received prior therapy with CDK4/6 inhibitors. Median PFS was significantly shorter in this subgroup (p=0.025). There was also a trend towards a longer PFS in patients with grade 3 breast cancer (p=0.085) and in patients receiving everolimus as first-line treatment (p=0.081). Some long responses were noted, with four patients exhibiting a PFS >5 years., Conclusion: These real-life data show that everolimus in combination with AI in patients with HER2-negative, HR-positive advanced breast cancer is an effective treatment with an acceptable toxicity profile., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2024
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36. Reduction of Tumor Biomarkers from very High to Normal and Extensive Metastatic Lesions to Undetectability in a Patient With Stage IV HER2-positive Breast Cancer Treated With Low-dose Trastuzumab Deruxtecan in Combination With Oral Recombinant Methioninase and a Low-methionine Diet.
- Author
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Sato M, Han Q, Mori R, Mizuta K, Kang BM, Morinaga S, Kobayashi N, Ichikawa Y, Nakajima A, and Hoffman RM
- Subjects
- Humans, Female, Aged, Biomarkers, Tumor, Trastuzumab therapeutic use, Methionine, Racemethionine, Diet, Receptor, ErbB-2, Breast Neoplasms drug therapy, Immunoconjugates, Camptothecin analogs & derivatives, Carbon-Sulfur Lyases
- Abstract
Background/aim: Breast cancer is the most common and the deadliest cancer among women in the world. Treatment options for HER2-positive metastatic breast cancer patients are limited. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC), has recently been introduced as second-line chemotherapy for HER2-positive metastatic breast cancer. The aim of the present study was to evaluate the efficacy of methionine restriction with oral recombinant methioninase (o-rMETase) and a low-methionine diet combined with T-DXd, on a patient with HER2-positive recurrent stage IV breast cancer., Case Report: A 66-year-old female was diagnosed with HER2-positive metastatic breast cancer. Computed tomography (CT) indicated peritoneal dissemination, thickening of the sigmoid colon and splenic flexure and widespread bone metastases. The patient was previously treated with fulvestrant, trastuzumab, pertuzumab, paclitaxel and capecitabine which were ineffective. T-DXd was administered as a second-line chemotherapy. Since the patient experienced strong side effects, the dose of T-Dxd was decreased. The patient began methionine restriction using o-rMETase and a low-methionine diet along with T-DXd. After the start of the combined treatment, CA15-3 and CA27.29, tumor markers for breast cancer, decreased rapidly from a very high level. The levels of both tumor markers are currently normal. Additionally, peritoneal-dissemination nodules, ascites and the thickness of the sigmoid colon and splenic flexure are no longer detected on CT. The patient maintains a high performance status, without severe side effects of the combination treatment., Conclusion: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with T-DXd as second-line chemotherapy, was highly effective in a patient with HER2-positive stage IV breast cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2024
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37. Real-world comparative effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer.
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Robert N, Chen C, Kim S, Zhang Z, Aguilar KM, Wang Y, Li B, Gaffney M, Huang X, and McRoy L
- Subjects
- Humans, Female, Aromatase Inhibitors therapeutic use, Cohort Studies, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols adverse effects, Retrospective Studies, Breast Neoplasms pathology, Piperazines, Pyridines
- Abstract
Aim: Provide real-world data on palbociclib as evidence of effectiveness in patient populations from routine clinical practice. Methods: This was a retrospective, observational cohort study of patients with HR+/HER2- metastatic breast cancer treated with palbociclib plus aromatase inhibitor (AI) or AI alone as first-line therapy within the US Oncology Network. Results: Patients treated with palbociclib plus AI (n = 838) versus AI alone (n = 450) had a numerically longer median overall survival (42.1 vs 35.7 months; hazard ratio [HR] = 0.90 [95% CI: 0.75-1.07]; p = 0.117) and a significantly extended real-world progression-free survival (21.0 vs 15.7 months; HR = 0.75 [95% CI: 0.64-0.88]; p = 0.0002) after normalized inverse probability treatment weighting. Conclusion: These real-world results support the use of palbociclib plus AI as first-line treatment in routine clinical practice for patients with HR+/HER2- metastatic breast cancer.
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- 2024
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38. Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer.
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Li Y, Qin J, Chen G, Wu W, and Sun X
- Subjects
- Humans, Female, Prognosis, Biomarkers, Tumor, Disease-Free Survival, Receptor, ErbB-2, Breast Neoplasms pathology, Brain Neoplasms
- Abstract
Background: Thrombospondin-1 (THBS1) is a secretory adhesive glycoprotein involved in the progression of multiple malignancies, including breast cancer. However, the clinical significance and prognostic role of plasma THBS1 in breast cancer have yet to be clarified., Methods: Plasma THBS1 levels in 627 breast cancer patients were analyzed by enzyme-linked immunosorbent assay. Bone marrow blood was drawn from the anterior/posterior superior iliac spine to detect the presence of disseminated tumor cells (DTCs). The effects of plasma THBS1 on the clinicopathological characteristics and survival prediction of breast cancer patients were explored., Results: Plasma THBS1 did not correlate with overall survival, breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) in the entire breast cancer cohort. Notably, HER2-enriched patients with high-plasma THBS1 levels had significantly shorter BCSS (P = 0.027) and DDFS (P = 0.011) than those with low levels. Multivariate analyses revealed that plasma THBS1 was an independent prognostic marker of BCSS (P = 0.026) and DDFS (P = 0.007) in HER2-enriched patients. THBS1 levels were 24% higher in positive DTC patients than in negative DTC patients (P = 0.031), and high levels were significantly associated with poor BCSS in positive DTC patients (HR 2.08, 95% CI 1.17-3.71; P = 0.019). Moreover, high-plasma THBS1 levels were specifically associated with an increased occurrence of brain metastasis in HER2-enriched patients (P = 0.041)., Conclusion: These findings suggest that plasma THBS1 may be serving as an unfavorable prognosis predictor for HER2-enriched breast cancer and justifies the need for further research., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
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- 2024
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39. Tucatinib Combination Treatment After Trastuzumab-Deruxtecan in Patients With ERBB2-Positive Metastatic Breast Cancer.
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Frenel JS, Zeghondy J, Guérin-Charbonnel C, Mailliez A, Volant E, Poumeaud F, Patsouris A, Arnedos M, Bailleux C, Cabal J, Galland L, de Nonneville A, Guiu S, Dalenc F, Pistilli B, Bachelot T, Pierga JY, Le Du F, Bocquet F, Larrouquere L, and Loirat D
- Subjects
- Humans, Middle Aged, Female, Capecitabine therapeutic use, Cohort Studies, Prospective Studies, Trastuzumab therapeutic use, Disease Progression, Receptor, ErbB-2, Breast Neoplasms drug therapy, Brain Neoplasms, Oxazoles, Pyridines, Quinazolines
- Abstract
Importance: Little is known regarding the outcomes associated with tucatinib combined with trastuzumab and capecitabine (TTC) after trastuzumab-deruxtecan exposure among patients with ERBB2 (previously HER2)-positive metastatic breast cancer (MBC)., Objective: To investigate outcomes following TTC treatment in patients with ERBB2-positive MBC who had previously received trastuzumab-deruxtecan., Design, Setting, and Participants: This cohort study included all patients with MBC who were treated in 12 French comprehensive cancer centers between August 1, 2020, and December 31, 2022., Exposure: Tucatinib combined with trastuzumab and capecitabine administered at the recommended dose., Main Outcomes and Measures: Clinical end points included progression-free survival (PFS), time to next treatment (TTNT), overall survival (OS), and overall response rate (ORR)., Results: A total of 101 patients with MBC were included (median age, 56 [range, 31-85] years). The median number of prior treatment lines for metastatic disease at TTC treatment initiation was 4 (range, 2-15), including 82 patients (81.2%) with previous trastuzumab and/or pertuzumab and 94 (93.1%) with previous ado-trastuzumab-emtansine) exposure. The median duration of trastuzumab-deruxtecan treatment was 8.9 (range, 1.4-25.8) months, and 82 patients (81.2%) had disease progression during trastuzumab-deruxtecan treatment, whereas 18 (17.8%) had stopped trastuzumab-deruxtecan for toxic effects and 1 (1.0%) for other reasons. Tucatinib combined with trastuzumab and capecitabine was provided as a third- or fourth-line treatment in 37 patients (36.6%) and was the immediate treatment after trastuzumab-deruxtecan in 86 (85.1%). With a median follow-up of 11.6 (95% CI, 10.5-13.4) months, 76 of 101 patients (75.2%) stopped TTC treatment due to disease progression. The median PFS was 4.7 (95% CI, 3.9-5.6) months; median TTNT, 5.2 (95% CI, 4.5-7.0) months; and median OS, 13.4 (95% CI, 11.1 to not reached [NR]) months. Patients who received TTC immediately after trastuzumab-deruxtecan had a median PFS of 5.0 (95% CI, 4.2-6.0) months; median TTNT of 5.5 (95% CI, 4.8-7.2) months, and median OS of 13.4 (95% CI, 11.9-NR) months. Those who received TTC due to trastuzumab-deruxtecan toxicity-related discontinuation had a median PFS of 7.3 (95% CI, 3.0-NR) months. Best ORR was 29 of 89 patients (32.6%). Sixteen patients with active brain metastasis had a median PFS of 4.7 (95% CI, 3.0-7.3) months, median TTNT of 5.6 (95% CI, 4.4 to NR), and median OS of 12.4 (95% CI, 8.3-NR) months., Conclusions and Relevance: In this study, TTC therapy was associated with clinically meaningful outcomes in patients with ERBB2-positive MBC after previous trastuzumab-deruxtecan treatment, including those with brain metastases. Prospective data on optimal drug sequencing in this rapidly changing therapeutic landscape are needed.
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- 2024
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40. Anatomy Versus Biology: What Guides Chemotherapy Decisions in Older Patients With Breast Cancer?
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Record SM, Thomas SM, Tian WM, van den Bruele AB, Chiba A, DiLalla G, DiNome ML, Kimmick G, Rosenberger LH, Woriax HE, Hwang ES, and Plichta JK
- Subjects
- Humans, Aged, Female, Receptor, ErbB-2, Sentinel Lymph Node Biopsy, Proportional Hazards Models, Biology, Axilla pathology, Lymph Node Excision, Breast Neoplasms pathology
- Abstract
Introduction: With the increasing utilization of genomic assays, such as the Oncotype DX recurrence score (RS), the relevance of anatomic staging has been questioned for select older patients with breast cancer. We sought to evaluate differences in chemotherapy receipt and/or survival among older patients based on RS and sentinel lymph node biopsy (SLNB) receipt/result., Methods: Patients aged ≥ 65 diagnosed with pT1-2/cN0/M0 hormone-receptor-positive (HR+)/HER2-breast cancer (2010-2019) were selected from the National Cancer Database. Logistic regression was used to identify factors associated with chemotherapy receipt. Cox proportional hazards models were used to estimate the association of RS/SLNB group with overall survival. A cost-benefit study was also performed., Results: Of the 75,428 patients included, the majority had an intermediate RS (58.2% versus 27.9% low, 13.8% high) and were SLNB- (85.1% versus 11.6% SLNB+, 3.3% none). Chemotherapy was recommended for 13,442 patients (17.8%). After adjustment, chemotherapy receipt was more likely with higher RS and SLNB+. After adjustment, SLNB receipt/result was only associated with overall survival among those with an intermediate RS. However, returning to the OR for SLNB is not cost-effective., Conclusions: SLNB receipt/result was associated with survival for those with an intermediate RS, but not a low or high RS, suggesting that an SLNB may indeed be unnecessary for select older patients with breast cancer., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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41. Cardiovascular complications of ribociclib in breast cancer patients.
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Fiste O, Mavrothalassitis E, Apostolidou K, Trika C, Liontos M, Koutsoukos K, Kaparelou M, Dimitrakakis C, Gavriatopoulou M, Dimopoulos MA, and Zagouri F
- Subjects
- Female, Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Protein Kinase Inhibitors therapeutic use, Quality of Life, Receptor, ErbB-2, Clinical Trials as Topic, Aminopyridines, Breast Neoplasms complications, Breast Neoplasms drug therapy, Purines
- Abstract
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have unprecedentedly advanced hormone-dependent breast cancer treatment paradigm. In the metastatic setting, ribociclib has consistently demonstrated survival benefit in pre-, peri-, and postmenopausal patients, conjugating efficacy with health-related quality of life preservation. Accordingly, the emergence of cardiac and/or vascular adverse events related to this novel targeted agent is gaining significant interest. This narrative review provides an overview of the incidence and spectrum of cardiovascular toxicity, in both clinical trial framework and real-world evidence. The potential pathogenetic mechanism, along with the available diagnostic parameters including biomarkers, and proper management, are also summarized., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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42. Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy.
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Ye HS, Zhou D, Li H, Lv J, Huang HQ, She JJ, Nie JH, Li TT, Lu MD, Du BL, Yang SQ, Chen PX, Li S, Ye GL, Luo W, and Liu J
- Subjects
- Humans, Female, Neoadjuvant Therapy, Disease-Free Survival, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms pathology
- Abstract
Background: 13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy., Methods: OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests., Results: Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST., Conclusions: The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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43. Association of clinical biomarkers and response to neoadjuvant therapy in breast cancer.
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Feeney G, Waldron R, Miller N, Malone C, Sweeney K, McLaughlin R, Lowery A, Barry K, and Kerin M
- Subjects
- Humans, Adult, Middle Aged, Female, Neoadjuvant Therapy, Lymphocytes, Neutrophils, Biomarkers, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Receptor, ErbB-2, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Triple Negative Breast Neoplasms pathology
- Abstract
Introduction: Neoadjuvant therapy is an essential component of multimodality therapy for locally advanced breast adenocarcinoma (BC). Complete pathologic response (pCR) is a useful surrogate for long-term oncologic outcome., Aim: To assess the association between clinicopathologic, molecular and immunological markers and treatment response to neoadjuvant therapy in BC., Methods: BC patients undergoing neoadjuvant therapy were identified from a prospectively maintained institutional database. Serum haematological/biochemical values, histopathologic, immunohistochemical data and TNM stage were obtained from electronic records. Patients were categorised into complete responders vs non-complete responders and responders vs non-responders. Statistical analysis was performed via SPSS., Results: Overall, 299 BC patients were included. The average age was 49.8 ± 11.5 years. A pCR was evident in 22.6% (n = 69). pCR was associated with early T stage and non-luminal subtypes (HER2 enriched [HER2 +] and triple negative [TNBC]). The neutrophil-lymphocyte ratio (NLR) pre-operatively was lower in patients with a pCR (p = 0.02). The lymphocyte-CRP ratio (LCR) was also slightly reduced in responders (p = 0.049) at diagnosis. A pre-op NLR greater than 2 was not found to be a significant predictive factor (p = 0.071) on multivariable logistic regression analysis. T stage at diagnosis (p = 0.024), N stage (p = 0.001) and breast cancer subtype (p = 0.0001) were also determined to be significant predictive factors of complete response., Conclusion: pCR was more likely in patients with less advanced disease in BC. The presence of HER2 + or TNBC in BC also increases the likelihood of pCR. Neoadjuvant therapy stimulates the systemic inflammatory response; however, a reduced baseline NLR may be associated with increased pCR. Confirmation with larger datasets is required., (© 2023. The Author(s).)
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- 2024
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44. Discrimination between human epidermal growth factor receptor 2 (HER2)-low-expressing and HER2-overexpressing breast cancers: a comparative study of four MRI diffusion models.
- Author
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Mao C, Hu L, Jiang W, Qiu Y, Yang Z, Liu Y, Wang M, Wang D, Su Y, Lin J, Yan X, Cai Z, Zhang X, and Shen J
- Subjects
- Female, Humans, Prospective Studies, Receptors, Progesterone, Diffusion Magnetic Resonance Imaging, Receptors, Estrogen metabolism, Breast Neoplasms pathology, Receptor, ErbB-2
- Abstract
Objectives: To determine the value of conventional DWI, continuous-time random walk (CTRW), fractional order calculus (FROC), and stretched exponential model (SEM) in discriminating human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC)., Methods: This prospective study included 158 women who underwent DWI, CTRW, FROC, and SEM and were pathologically categorized into the HER2-zero-expressing group (n = 10), HER2-low-expressing group (n = 86), and HER2-overexpressing group (n = 62). Nine diffusion parameters, namely ADC, α
CTRW , βCTRW , DCTRW , βFROC , DFROC , μFROC , αSEM , and DDCSEM of the primary tumor, were derived from four diffusion models. These diffusion metrics and clinicopathologic features were compared between groups. Logistic regression was used to determine the optimal diffusion metrics and clinicopathologic variables for classifying the HER2-expressing statuses. Receiver operating characteristic (ROC) curves were used to evaluate their discriminative ability., Results: The estrogen receptor (ER) status, progesterone receptor (PR) status, and tumor size differed between HER2-low-expressing and HER2-overexpressing groups (p < 0.001 to p = 0.009). The αCTRW , DCTRW , βFROC , DFROC , μFROC , αSEM , and DDCSEM were significantly lower in HER2-low-expressing BCs than those in HER2-overexpressing BCs (p < 0.001 to p = 0.01). Further multivariable logistic regression analysis showed that the αCTRW was the single best discriminative metric, with an area under the curve (AUC) being higher than that of ADC (0.802 vs. 0.610, p < 0.05); the addition of ER status, PR status, and tumor size to the αCTRW improved the AUC to 0.877., Conclusions: The αCTRW could help discriminate the HER2-low-expressing and HER2-overexpressing BCs., Clinical Relevance Statement: Human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC) might also benefit from the HER2-targeted therapy. Prediction of HER2-low-expressing BC or HER2-overexpressing BC is crucial for appropriate management. Advanced continuous-time random walk diffusion MRI offers a solution to this clinical issue., Key Points: • Human epidermal receptor 2 (HER2)-low-expressing BC had lower αCTRW , DCTRW , βFROC , DFROC , μFROC , αSEM , and DDCSEM values compared with HER2-overexpressing breast cancer. • The αCTRW was the single best diffusion metric (AUC = 0.802) for discrimination between the HER2-low-expressing and HER2-overexpressing breast cancers. • The addition of αCTRW to the clinicopathologic features (estrogen receptor status, progesterone receptor status, and tumor size) further improved the discriminative ability., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)- Published
- 2024
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45. Is Pertuzumab Plus Trastuzumab Without Chemotherapy a Reasonable Treatment for ERBB2-Positive Metastatic Breast Cancer?-Reply.
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Huober J, Thürlimann B, and Dietrich D
- Subjects
- Humans, Female, Trastuzumab, Antibodies, Monoclonal, Humanized therapeutic use, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms pathology
- Published
- 2024
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46. Survival, treatment patterns, and costs of HER2+ metastatic breast cancer patients in Ontario between 2005 to 2020.
- Author
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Seung SJ, Saherawala H, Moldaver D, Shokar S, Ammendolea C, and Brezden-Masley C
- Subjects
- Female, Humans, Middle Aged, Ado-Trastuzumab Emtansine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Ontario epidemiology, Receptor, ErbB-2, Retrospective Studies, Trastuzumab therapeutic use, Adult, Aged, Breast Neoplasms drug therapy, Breast Neoplasms epidemiology
- Abstract
Background: To enable the integration of novel therapies, it is critical to understand current long-term outcomes in HER2-positive metastatic breast cancer (mBC), including survival, treatment patterns, and costs. We sought to define these outcomes among patients with mBC in Ontario., Methods: We conducted a retrospective population-level study in Ontario women diagnosed with breast cancer of any stage between January 1, 2005 and December 31, 2019, with follow-up until December 31, 2020. HER2-positivity was based on receipt of a HER2-targeted therapy (HER2-TT) in the first line (1L) metastatic setting. Administrative databases at ICES were used to assess outcomes., Results: In Ontario, 2557 patients were diagnosed with mBC and received a HER2-TT, and of these 1606 were diagnosed with early-stage (stage I-III) that became metastatic (recurrent), while 951 were diagnosed with late stage/de novo mBC (stage IV). The average age of all patients was 54.8 years ± 12.7 years. Treatment regimens that included pertuzumab and trastuzumab (cohort name: pert_tras) were the most frequently used HER2-TT for 1L mBC (51.4%), while T-DM1 was the most frequent therapy (87.5%) in second line (2L). The median overall survival (mOS) from initiation of 1L pert_tras was not reached, whereas mOS from initiation of T-DM1 in 2L was 18.7 months. The overall mean cost per patient on pert_tras during 1L was $267,282. The main cost drivers were the cost of systemic therapy, followed by cancer clinic visits, with a mean cost per patient at $158,961 and $73,882, respectively., Conclusion: The baseline characteristics and treatment patterns for patients who received HER2-TT in our study align with previously reported results. However, the mOS observed for 2L T-DM1 was shorter than that found in pivotal, clinical trial literature. As expected, anti-cancer systemic therapy costs were the main contributor to the over quarter-million dollar mean cost per patient on pert_tras in 1L., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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47. Efficacy of Neratinib Plus Capecitabine in the Subgroup of Patients with Central Nervous System Involvement from the NALA Trial.
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Hurvitz, Sara A., Saura, Cristina, Oliveira, Mafalda, Trudeau, Maureen E., Moy, Beverly, Delaloge, Suzette, Gradishar, William, Kim, Sung‐Bae, Haley, Barbara, Ryvo, Larisa, Dai, Ming‐Shen, Milovanov, Vladimir, Alarcón, Jesús, Kalmadi, Sujith, Cronemberger, Eduardo, Souza, Cristiano, Landeiro, Luciana, Bose, Ron, Bebchuk, Judith, and Kabbinavar, Fairooz
- Subjects
THERAPEUTIC use of antimetabolites ,THERAPEUTIC use of antineoplastic agents ,CONFIDENCE intervals ,METASTASIS ,CENTRAL nervous system tumors ,ANTINEOPLASTIC agents ,PROTEIN-tyrosine kinase inhibitors ,TREATMENT effectiveness ,COMPARATIVE studies ,ANTIMETABOLITES ,DESCRIPTIVE statistics ,BREAST tumors - Abstract
Background: Neratinib has efficacy in central nervous system (CNS) metastases from HER2‐positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C). Materials and Methods: NALA was a randomized, active‐controlled trial in patients who received two or more previous HER2‐directed regimens for HER2‐positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m2 twice daily) orally. Independently adjudicated progression‐free survival (PFS), overall survival (OS), and CNS endpoints were considered. Results: Of 621 patients enrolled, 101 (16.3%) had known CNS metastases at baseline (N + C, n = 51; L + C, n = 50); 81 had received prior CNS‐directed radiotherapy and/or surgery. In the CNS subgroup, mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.41–1.05), and mean OS through 48 months was 16.4 versus 15.4 months (HR, 0.90; 95% CI, 0.59–1.38). At 12 months, cumulative incidence of interventions for CNS disease was 25.5% for N + C versus 36.0% for L + C, and cumulative incidence of progressive CNS disease was 26.2% versus 41.6%, respectively. In patients with target CNS lesions at baseline (n = 32), confirmed intracranial objective response rates were 26.3% and 15.4%, respectively. No new safety signals were observed. Conclusion: These analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2‐positive MBC. Implications for Practice: In a subgroup of patients with central nervous system (CNS) metastases from HER2‐positive breast cancer after two or more previous HER2‐directed regimens, the combination of neratinib plus capecitabine was associated with improved progression‐free survival and CNS outcomes compared with lapatinib plus capecitabine. These findings build on previous phase II and III studies describing efficacy of neratinib in the prevention and treatment of CNS metastases, and support a role for neratinib as a systemic treatment option in the management of patients with HER2‐positive brain metastases following antibody‐based HER2‐directed therapies. This article reports outcomes among HER2‐positive breast cancer patients with central nervous system metastases at baseline from the phase III NALA trial of neratinib plus capecitabine versus lapatinib plus capecitabine. [ABSTRACT FROM AUTHOR]
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- 2021
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48. Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer
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Lajos Pusztai, Gabriel N. Hortobagyi, Bryan T. Hennessy, Massimo Cristofanilli, Chafika Mazouni, Fabrice Andre, Attila Tordai, W. Fraser Symmans, Cornelia Liedtke, Marjorie C. Green, Ana M. Gonzalez-Angulo, Kenneth R. Hess, and Jaime A. Mejia
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Adult ,Oncology ,medicine.medical_specialty ,Cancer Research ,Neoplasm, Residual ,Neoplasms, Hormone-Dependent ,Receptor, ErbB-2 ,medicine.medical_treatment ,Estrogen receptor ,Breast Neoplasms ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Prospective Studies ,Survival rate ,Neoadjuvant therapy ,Triple-negative breast cancer ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Gynecology ,business.industry ,Carcinoma, Ductal, Breast ,Cancer ,Triple Negative Breast Neoplasms ,Middle Aged ,Prognosis ,medicine.disease ,Neoadjuvant Therapy ,Survival Rate ,Receptors, Estrogen ,Chemotherapy, Adjuvant ,Female ,Breast disease ,Neoplasm Recurrence, Local ,Receptors, Progesterone ,business - Abstract
PURPOSE Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC. PATIENTS AND METHODS Analysis of a prospectively collected clinical database was performed. We included 1,118 patients who received neoadjuvant chemotherapy at M.D. Anderson Cancer Center for stage I-III breast cancer from 1985 to 2004 and for whom complete receptor information were available. Clinical and pathologic parameters, pathologic complete response rates (pCR), survival measurements, and organ-specific relapse rates were compared between patients with TNBC and non-TNBC. RESULTS Two hundred fifty-five patients (23%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates (22% v 11%; P = .034), but decreased 3-year progression-free survival rates ( P < .0001) and 3-year overall survival (OS) rates ( P < .0001). TNBC was associated with increased risk for visceral metastases ( P = .0005), lower risk for bone recurrence ( P = .027), and shorter postrecurrence survival ( P < .0001). Recurrence and death rates were higher for TNBC only in the first 3 years. If pCR was achieved, patients with TNBC and non-TNBC had similar survival ( P = .24). In contrast, patients with residual disease (RD) had worse OS if they had TNBC compared with non-TNBC ( P < .0001). CONCLUSION Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR have excellent survival. However, patients with RD after neoadjuvant chemotherapy have significantly worse survival if they have TNBC compared with non-TNBC, particularly in the first 3 years.
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- 2023
49. Genomic characterisation of hormone receptor-positive breast cancer arising in very young women
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Luen, SJ, Viale, G, Nik-Zainal, S, Savas, P, Kammler, R, Dell'Orto, P, Biasi, O, Degasperi, A, Brown, LC, Láng, I, MacGrogan, G, Tondini, C, Bellet, M, Villa, F, Bernardo, A, Ciruelos, E, Karlsson, P, Neven, P, Climent, M, Müller, B, Jochum, W, Bonnefoi, H, Martino, S, Davidson, NE, Geyer, C, Chia, SK, Ingle, JN, Coleman, R, Solbach, C, Thürlimann, B, Colleoni, M, Coates, AS, Goldhirsch, A, Fleming, GF, Francis, PA, Speed, TP, Regan, MM, Loi, S, Nik-Zainal, Serena [0000-0001-5054-1727], and Apollo - University of Cambridge Repository
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young women ,breast cancer ,Oncology ,Receptor, ErbB-2 ,Class I Phosphatidylinositol 3-Kinases ,genomics ,Humans ,Female ,Breast Neoplasms ,hormone receptor positive ,prognosis ,Hematology ,Aged - Abstract
BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (
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- 2023
50. Prediction of breast cancer molecular subtypes on DCE-MRI using convolutional neural network with transfer learning between two centers.
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Zhang, Yang, Chen, Jeon-Hor, Lin, Yezhi, Chan, Siwa, Zhou, Jiejie, Chow, Daniel, Chang, Peter, Kwong, Tiffany, Yeh, Dah-Cherng, Wang, Xinxin, Parajuli, Ritesh, Mehta, Rita S., Wang, Meihao, and Su, Min-Ying
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CONVOLUTIONAL neural networks , *DEEP learning , *SIGNAL convolution , *BREAST cancer , *RECURRENT neural networks , *MACHINE learning - Abstract
Objectives: To apply deep learning algorithms using a conventional convolutional neural network (CNN) and a recurrent CNN to differentiate three breast cancer molecular subtypes on MRI. Methods: A total of 244 patients were analyzed, 99 in training dataset scanned at 1.5 T and 83 in testing-1 and 62 in testing-2 scanned at 3 T. Patients were classified into 3 subtypes based on hormonal receptor (HR) and HER2 receptor: (HR+/HER2−), HER2+, and triple negative (TN). Only images acquired in the DCE sequence were used in the analysis. The smallest bounding box covering tumor ROI was used as the input for deep learning to develop the model in the training dataset, by using a conventional CNN and the convolutional long short-term memory (CLSTM). Then, transfer learning was applied to re-tune the model using testing-1(2) and evaluated in testing-2(1). Results: In the training dataset, the mean accuracy evaluated using tenfold cross-validation was higher by using CLSTM (0.91) than by using CNN (0.79). When the developed model was applied to the independent testing datasets, the accuracy was 0.4–0.5. With transfer learning by re-tuning parameters in testing-1, the mean accuracy reached 0.91 by CNN and 0.83 by CLSTM, and improved accuracy in testing-2 from 0.47 to 0.78 by CNN and from 0.39 to 0.74 by CLSTM. Overall, transfer learning could improve the classification accuracy by greater than 30%. Conclusions: The recurrent network using CLSTM could track changes in signal intensity during DCE acquisition, and achieved a higher accuracy compared with conventional CNN during training. For datasets acquired using different settings, transfer learning can be applied to re-tune the model and improve accuracy. Key Points: • Deep learning can be applied to differentiate breast cancer molecular subtypes. • The recurrent neural network using CLSTM could track the change of signal intensity in DCE images, and achieved a higher accuracy compared with conventional CNN during training. • For datasets acquired using different scanners with different imaging protocols, transfer learning provided an efficient method to re-tune the classification model and improve accuracy. [ABSTRACT FROM AUTHOR]
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- 2021
- Full Text
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