Cancer Research and Treatment

Original Articles

Breast cancer

Combination Therapy of Pyrotinib and Metronomic Vinorelbine in HER2+ Advanced Breast Cancer after Trastuzumab Failure (PROVE): A Prospective Phase 2 Study: Chunfang Hao, Xu Wang, Yehui Shi, Zhongsheng Tong, Shufen Li, Xiaodong Liu, Lan Zhang, Jie Zhang, Wenjing Meng, Li Zhang; Cancer Res Treat. 2025;57(2):434-442. Published online August 9, 2024; DOI: https://doi.org/10.4143/crt.2024.340

Purpose
Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients.
Materials and Methods
In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.
Results
From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs.
Conclusion
Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Citations

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Adjuvant Metronomic Chemotherapy After Surgery in pT1-T2 N0 M0 HER2-Positive and ER/PR-Positive Breast Cancer Plus Targeted Therapy, Anti-Hormonal Therapy, and Radiotherapy, with or Without Immunotherapy: A New Operational Proposal
Luca Roncati
Cancers.2025; 17(8): 1323. CrossRef

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Trastuzumab Biosimilar (HLX02), Pertuzumab Plus Chemotherapy in Patients with HER2-Positive Metastatic Breast Cancer after Progression of Trastuzumab: A Prospective, Phase II Study: Ruyan Zhang, Xiaoran Liu, Guohong Song, Yan Zhang, Huiping Li; Cancer Res Treat. 2024;56(3):795-801. Published online December 20, 2023; DOI: https://doi.org/10.4143/crt.2023.1151

Abstract PDF PubReader ePub: Purpose
This study aims to evaluate the efficacy and safety of trastuzumab biosimilar (HLX02) in combination with pertuzumab and chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) after progression of trastuzumab.
Materials and Methods
In this prospective, single-arm, phase II study, patients with HER2-positive MBC after progression of trastuzumab received pertuzuamb, HLX02, and chemotherapy in Beijing Cancer Hospital from March 2020 to December 2022. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov (NCT05188495).
Results
A total of 45 patients were included in this study. Twelve patients (26.7%) were treated in second-line and 33 patients (73.3%) were in third-line and later setting. Eighty percent and 15.5% patients had previously received pyrotinib/lapatinib and T-DM1, respectively. With a median follow-up of 24.4 months (range, 1.2 to 43.9 months), the median PFS was 7.6 months (95% confidence interval, 4.3 to 10.9), OS was not reached, the ORR was 31.1%, and DCR was 91.1%. The treatment was well tolerated.
Conclusion
The combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited promising efficacy and a favorable safety profile as second- and beyond-line treatment in HER2-positive MBC.

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Gastrointestinal cancer

Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis: Ting Xu, Xicheng Wang, Ying Xin, Zhenghang Wang, Jifang Gong, Xiaotian Zhang, Yanyan Li, Congcong Ji, Yu Sun, Feilong Zhao, Depei Huang, Yuezong Bai, Jian Li, Lin Shen; Cancer Res Treat. 2023;55(2):626-635. Published online December 23, 2022; DOI: https://doi.org/10.4143/crt.2022.1058

Abstract PDF Supplementary Material PubReader ePub

Purpose
The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC).
Materials and Methods
An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m² days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate.
Results
Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC.
Conclusion
Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

Citations

Citations to this article as recorded by

HER2-targeted therapy in colorectal cancer: a comprehensive review
Yeliz Benli, Helin Arıkan, Özge Akbulut-Çalışkan
Clinical and Translational Oncology.2025;[Epub] CrossRef
Enhancing treatment strategies for small bowel cancer: a clinical review of targeted therapy and immunotherapy approaches
Mehrshad Ebrahimpour, Hamidreza Hosseinzadeh, Farshad Abedi, Mohammad Moeini Nodeh, Abolghasem Allahyari, Amirhossein Sahebkar, Omid Arasteh
Naunyn-Schmiedeberg's Archives of Pharmacology.2024; 397(7): 4601. CrossRef
Drug combinations of camptothecin derivatives promote the antitumor properties
Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng
European Journal of Medicinal Chemistry.2024; 279: 116872. CrossRef
Functionalised Ligand-Based Nanomaterial Drug Targeting Approaches for Colorectal Cancer Therapy
Amol A. Dixit, Deepa S. Mandlik, Satish K. Mandlik
Recent Advances in Drug Delivery and Formulation.2024; 18(3): 170. CrossRef
Nimotuzumab and irinotecan synergistically induce ROS‐mediated apoptosis by endoplasmic reticulum stress and mitochondrial‐mediated pathway in cervical cancer
Fei Teng, Lujun Zhao
Biotechnology and Applied Biochemistry.2024;[Epub] CrossRef
Current Targeted Therapy for Metastatic Colorectal Cancer
Tomokazu Ohishi, Mika K. Kaneko, Yukihiro Yoshida, Atsuo Takashima, Yukinari Kato, Manabu Kawada
International Journal of Molecular Sciences.2023; 24(2): 1702. CrossRef
Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview
Jingjing Li, Xuanfu Xu
International Journal of General Medicine.2023; Volume 16: 1527. CrossRef
Mechanism of multidrug resistance to chemotherapy mediated by P‑glycoprotein (Review)
Yichen Tian, Yongrong Lei, Yani Wang, Jiejuan Lai, Jianhua Wang, Feng Xia
International Journal of Oncology.2023;[Epub] CrossRef
Successful treatment with trastuzumab plus chemotherapy as the first‑line regimen in advanced small bowel adenocarcinoma harboring HER2 amplification: A report of two cases
Jingwen Wang, Xia Zhu, Jiayan Chen, Fei Liu, Xi Tang
Oncology Letters.2023;[Epub] CrossRef

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Breast cancer

Real-World Evidence of Trastuzumab, Pertuzumab, and Docetaxel Combination as a First-Line Treatment for Korean Patients with HER2-Positive Metastatic Breast Cancer: Yong-Pyo Lee, Min-Sang Lee, HongSik Kim, Ji-Yeon Kim, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park; Cancer Res Treat. 2022;54(4):1130-1137. Published online January 17, 2022; DOI: https://doi.org/10.4143/crt.2021.1103

Abstract PDF Supplementary Material PubReader ePub

Purpose
Trastuzumab has markedly improved the survival outcomes of patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer, and dual blockade of HER2 using trastuzumab and pertuzumab in combination with taxanes (THP) has become a standard of care for HER2-positive metastatic breast cancer (MBC) worldwide since the CLEOPATRA trial. We assessed the outcomes of THP as a first-line treatment for Korean HER2-positive MBC patients in the real-world setting.
Materials and Methods
Between August 2008 and October 2020, we identified 228 HER2-positive MBC patients who received THP as a first-line palliative chemotherapy. We analyzed survival outcomes, efficacy, and adverse events of THP retrospectively.
Results
After a median follow-up duration of 28.7 months, median overall survival and progression-free survival were 58.3 months (95% confidence interval [CI], 36.6 to 80.0) and 19.1 months (95% CI, 16.2 to 21.9), respectively. Better survival outcomes were observed in patient who received docetaxel for more than six cycles. Patients exposed to anti-HER2 directed therapies in a perioperative setting had poor survival outcomes. The overall response rate was 86.8% with a complete response (CR) rate of 17.7%. Among responders, 16.7% of patients sustained THP over 35 months and showed better survivals and higher CR rates. Adverse events were comparable to those reported in previous studies.
Conclusion
In a real-world context, clinical outcomes of Korean HER2-positive MBC patients treated with THP were similar to those of patients in the CLEOPATRA trial. Much longer follow-up results would be warranted.

Citations

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Pertuzumab in Combination with Trastuzumab and Docetaxel as Adjuvant Doublet Therapy for HER2-Positive Breast Cancer: A Systematic Review
Ignacio Ventura, Nerea Pinilla Salcedo, Marcelino Pérez-Bermejo, Javier Pérez-Murillo, Manuel Tejeda-Adell, Francisco Tomás-Aguirre, María Ester Legidos-García, María Teresa Murillo-Llorente
International Journal of Molecular Sciences.2025; 26(5): 1908. CrossRef
Real-world impact of dual anti-HER2 antibodies on cardiac function in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer
Kelvin KH. Bao, Jeffrey CH. Chan, Jocelyn G. Chan, Leone Sutanto, Ka Man Cheung, Harry HY. Yiu
The Breast.2024; 73: 103612. CrossRef
Bilateral inflammatory recurrence of HER-2 positive breast cancer: a unique case report and literature review
Rong Qin, Xiangyang Wang, Tingting Fan, Ting Wu, Chao Lu, Xun Shao, Liang Yin
Frontiers in Oncology.2024;[Epub] CrossRef
Biosensing chips for cancer diagnosis and treatment: a new wave towards clinical innovation
Muhammad Javed Iqbal, Zeeshan Javed, Jesús Herrera-Bravo, Haleema Sadia, Faiza Anum, Shahid Raza, Arifa Tahir, Muhammad Naeem Shahwani, Javad Sharifi-Rad, Daniela Calina, William C. Cho
Cancer Cell International.2022;[Epub] CrossRef

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Gastrointestinal cancer

Trends in Chemotherapy Patterns and Survival of Patients with Advanced Gastric Cancer over a 16-Year Period: Impact of Anti-HER2–Targeted Agent in the Real-World Setting: Dong-Hoe Koo, Min-Hee Ryu, Mi-Yeon Lee, Heejung Chae, Eo Jin Kim, Mee-Sun Moon, Yoon-Koo Kang; Cancer Res Treat. 2021;53(2):436-444. Published online October 6, 2020; DOI: https://doi.org/10.4143/crt.2020.725

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns.
Materials and Methods
A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4).
Results
There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The OS rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% CI, 15.5–20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8–11.6).
Conclusion
The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.

Citations

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Treatment Modalities and Survival Outcomes in Gastric Cancer: Insights From Najran, Saudi Arabia
Ahmed M Badheeb, Ibrahim A Alyami, Ahlam Y Alyami, Mohammed Alyami, Mugahed Al Walani, Samer Alkarak, Abdelaziz A Aman, Fahad M Albaiji, Ali G Al Masad, Abdullah S Alyami, Islam A Seada, Abdullah Abu Bakar
Cureus.2025;[Epub] CrossRef
Treatment patterns and outcomes in advanced or metastatic gastric/gastroesophageal junction adenocarcinoma in China
Jingdong Zhang, Guangyu Wang, Xianhe Xie, Wensheng Pan, Qian Dong, Nianhai Zhang, Jie Dong, Li Zhou, Chan Zhou, Jinnan Li, Grace Segall, Yanqiao Zhang
Future Oncology.2025; 21(10): 1179. CrossRef
Factors associated with the efficacy of first-line nivolumab plus chemotherapy in advanced gastric cancer patients with deficient mismatch repair
Young-Gyu Park, Hyung-Don Kim, Jaewon Hyung, Young Soo Park, Min-Hee Ryu
Gastric Cancer.2024; 27(4): 840. CrossRef
Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13)
Dong-Hoe Koo, Minkyu Jung, Yeul Hong Kim, Hei-Cheul Jeung, Dae Young Zang, Woo Kyun Bae, Hyunki Kim, Hyo Song Kim, Choong-kun Lee, Woo Sun Kwon, Hyun Cheol Chung, Sun Young Rha
Cancer Research and Treatment.2024; 56(4): 1136. CrossRef
Breakthroughs in the Systemic Treatment of HER2-Positive Advanced/Metastatic Gastric Cancer: From Singlet Chemotherapy to Triple Combination
Sun Young Rha, Hyun Cheol Chung
Journal of Gastric Cancer.2023;[Epub] CrossRef
Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab
Kyunghye Bang, Jaekyung Cheon, Young Soo Park, Hyung-Don Kim, Min-Hee Ryu, Yangsoon Park, Meesun Moon, Hyungeun Lee, Yoon-Koo Kang
Gastric Cancer.2022; 25(4): 794. CrossRef
Clinicopathological features and CT findings of papillary gastric adenocarcinoma
Mengying Xu, Song Liu, Xiangmei Qiao, Lin Li, Changfeng Ji, Zhengyang Zhou
Abdominal Radiology.2022; 47(11): 3698. CrossRef
New prognostic model for patients with advanced gastric cancer: Fluoropyrimidine/platinum doublet for first-line chemotherapy
Dong-Hoe Koo, Min-Hee Ryu, Mi-Yeon Lee, Mee-Sun Moon, Yoon-Koo Kang
World Journal of Gastroenterology.2021; 27(48): 8357. CrossRef

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BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy: Sung-Bae Kim, In-Gu Do, Janice Tsang, Tae-You Kim, Yoon-Sim Yap, Gerardo Cornelio, Gyungyub Gong, Soonmyung Paik, Suee Lee, Ting-Ying Ng, Sarah Park, Ho-Suk Oh, Joanne Chiu, Joohyuk Sohn, Moonhee Lee, Young-Jin Choi, Eun Mi Lee, Kyong-Hwa Park, Christos Nathaniel, Jungsil Ro; Cancer Res Treat. 2019;51(4):1527-1539. Published online June 4, 2019; DOI: https://doi.org/10.4143/crt.2018.598

Abstract PDF PubReader ePub

Purpose
BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. Materials and Methods Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored.
Results
p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib.
Conclusion
The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

Citations

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PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Research and Treatment.2023; 55(2): 531. CrossRef
Discordance of PIK3CA mutational status between primary and metastatic breast cancer: a systematic review and meta-analysis
Justus Rosin, Ella Svegrup, Antonios Valachis, Ioannis Zerdes
Breast Cancer Research and Treatment.2023; 201(2): 161. CrossRef
Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data
Haizhu Chen, Xingbin Hu, Daquan Wang, Ying Wang, Yunfang Yu, Herui Yao
Translational Oncology.2023; 37: 101738. CrossRef
Comparison of PIK3CA Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations
Jessica W. Chen, Karthikeyan Murugesan, Justin Y. Newberg, Ethan S. Sokol, Heidi M. Savage, Thomas J. Stout, Sophia L. Maund, Katherine E. Hutchinson
JCO Precision Oncology.2022;[Epub] CrossRef
Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments
Ugo Testa, Germana Castelli, Elvira Pelosi
Medical Sciences.2020; 8(1): 18. CrossRef

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Early Decline in Left Ventricular Ejection Fraction Can Predict Trastuzumab-Related Cardiotoxicity in Patients with Breast Cancer: A Study Using 13 Years of Registry Data: Eun Kyoung Kim, Jinhyun Cho, Ji-Yeon Kim, Sung-A Chang, Sung-Ji Park, Jin Oh Choi, Sang Chol Lee, Jin Seok Ahn, Seung Woo Park, Young-Hyuck Im, Eun Seok Jeon, Yeon Hee Park; Cancer Res Treat. 2019;51(2):727-736. Published online September 4, 2018; DOI: https://doi.org/10.4143/crt.2018.262

Abstract PDF PubReader ePub

Purpose
While concerns regarding trastuzumab-related cardiac dysfunction (TRCD) in patients with breast cancer are increasing, there is a lack of evidence supporting the current recommendations for TRCD monitoring. We aimed to investigate the clinical predictors of TRCD in the adjuvant setting of human epidermal growth factor receptor 2–positive breast cancer patients.
Materials and Methods
From August 2003 to April 2016, consecutive 998 patients who were treated with adjuvant trastuzumab for breast cancer were retrospectively evaluated. TRCD was defined as a decrease ≥10% in left ventricular ejection fraction (LVEF), with a decline below the normal limit or symptomatic heart failure.
Results
Among 787 eligible patients who had complete data sets consisting of both baseline and follow-up assessment of left ventricular systolic function by echocardiography (mean age, 49.9±9.5 years), 58 (7.4%) developed TRCD. TRCD patients had lower baseline LVEF (63% [59–66] vs. 65% [61–68], p=0.016) and more frequently administered Adriamycin (98% vs. 89%, p=0.022) than those without TRCD. On follow-up echocardiography, a drop in LVEF ≥5% within the first 3 months was more frequent in TRCD patients (78.3% vs. 38.4%, p<0.001). Regardless of baseline LVEF and Adriamycin treatment, a drop in LVEF ≥5% within the first 3 months of trastuzumab administration was strongly associated with the development of TRCD (adjusted hazard ratio, 45.1[17.0–127.6], p<0.001).
Conclusion
The overall incidence of TRCD was 7.4% in Asian breast cancer patients treated with adjuvant trastuzumab. A decline in LVEF ≥5% within the first 3 months of trastuzumab initiation was strongly associated with TRCD development in patients with breast cancer.

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Yi Wang, Lixue Yin
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ABSDELL Model: Development and Internal Validation of a Risk Prediction Model of LVEF Decline in Breast Cancer Patients Treated With Trastuzumab
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Determinants of left ventricular ejection fraction and a novel method to improve its assessment of myocardial contractility
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Zhuyu Xu, Dandan Guo, Zhongliang Jiang, Rongsheng Tong, Peidu Jiang, Lan Bai, Lu Chen, Yuxuan Zhu, Chun Guo, Jianyou Shi, Dongke Yu
European Journal of Medicinal Chemistry.2019; 183: 111682. CrossRef

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Case Report

Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and Leptomeningeal Carcinomatosis: Won-Young Park, Han-Jo Kim, Kyoungha Kim, Sang-Byung Bae, Namsu Lee, Kyu-Taek Lee, Jong-Ho Won, Hee-Sook Park, Sang-Cheol Lee; Cancer Res Treat. 2016;48(2):843-847. Published online March 2, 2015; DOI: https://doi.org/10.4143/crt.2014.234

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Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.

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Original Articles

Serum HER2 as a Response Indicator to Various Chemotherapeutic Agents in Tissue HER2 Positive Metastatic Breast Cancer: Sun-Young Kong, Do Hoon Lee, Eun Sook Lee, Susan Park, Keun Seok Lee, Jungsil Ro; Cancer Res Treat. 2006;38(1):35-39. Published online February 28, 2006; DOI: https://doi.org/10.4143/crt.2006.38.1.35

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Purpose

The aim of study was to evaluate the usefulness of serum HER2 as a therapeutic response indicator in patients with HER2 positive metastatic breast cancer (MBC).

Materials and Methods

The levels of serum HER2 and CA15.3 were assayed in 148 serial serum samples from 50 HER2 positive MBC patients at both the baseline and follow-ups. The changes in the levels of serum HER2 and CA15.3 in relation to the tumor responses to the various chemotherapy regimens were monitored.

Results

The levels of serum HER2 and CA15.3 were elevated in 82% and 62% of tissue HER2 positive patients, respectively, prior to therapies, with the changes in both tumor markers showing statistical significance in relation to the tumor responses (p<0.01) in patients with elevated baseline serum markers.

Conclusion

The level of serum HER2 could be a valuable response indicator, not only for trastuzumab containing therapy, but also for other common MBC chemotherapeutic agents. Also, as it is more frequently elevated, the serum level of HER2 may also be a more useful tumor marker than CA15.3 in HER2 positive MBC.

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AlGaN/GaN HEMT Based Biosensor for Detection of the HER2 Antigen Spiked in Human Serum
Shivanshu Mishra, Pharyanshu Kachhawa, Prasenjit Mondal, Surajit Ghosh, Chaturvedula Tripura, Nidhi Chaturvedi
IEEE Transactions on Electron Devices.2022; 69(8): 4527. CrossRef
Amphiregulin confers trastuzumab resistance via AKT and ERK activation in HER2-positive breast cancer
Ji-Won Kim, Debora K. Kim, Ahrum Min, Kyung-Hun Lee, Hyun-Jin Nam, Jee Hyun Kim, Jin-Soo Kim, Tae-Yong Kim, Seock-Ah Im, In Ae Park
Journal of Cancer Research and Clinical Oncology.2016; 142(1): 157. CrossRef
The Significance of Serum HER2 Levels at Diagnosis on Intrinsic Subtype-Specific Outcome of Operable Breast Cancer Patients
Moo Hyun Lee, So-Youn Jung, Sun Hee Kang, Eun Jin Song, In Hae Park, Sun-Young Kong, Young Mee Kwon, Keun Seok Lee, Han-Sung Kang, Eun Sook Lee, Aamir Ahmad
PLOS ONE.2016; 11(10): e0163370. CrossRef
HER2 amplification level is not a prognostic factor for HER2-positive breast cancer with trastuzumab-based adjuvant treatment: a systematic review and meta-analysis
Qian-Qian Xu, Bo Pan, Chang-Jun Wang, Yi-Dong Zhou, Feng Mao, Yan Lin, Jing-Hong Guan, Song-Jie Shen, Xiao-Hui Zhang, Ya-Li Xu, Ying Zhong, Xue-Jing Wang, Yan-Na Zhang, Qiang Sun
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Serum HER2 levels are increased in cats with mammary carcinomas and predict tissue HER2 status
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Serum epidermal growth factor is associated with prognosis and hormone receptor status in patients with HER2-positive metastatic breast cancer treated with first-line trastuzumab plus taxane chemotherapy
Ji-Won Kim, Jee Hyun Kim, Seock-Ah Im, Kyung-Hun Lee, Jin-Soo Kim, Tae-Yong Kim, Sae-Won Han, Yoon Kyung Jeon, Do-Youn Oh, Tae-You Kim, In Ae Park
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Ji-Won Kim, Jee Hyun Kim, Seock-Ah Im, Yu Jung Kim, Hye-Suk Han, Jin-Soo Kim, Sae-Won Han, Yoon Kyung Jeon, Do-Youn Oh, Wonshik Han, Tae-You Kim, In Ae Park, Dong-Young Noh, Yung-Jue Bang
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The Prognostic Significance of the Overexpression of HER-2/ neu in Korean Gastric Carcinomas and the In Vitro Effects of Anti-HER-2/neu Antibody on Cell Growth in the Gastric Carcinoma Cell Lines: Seock Ah Im, Kyung Eun Lee, Eunmi Nam, Seung Hyun Nam, Do Yeun Kim, Chu Myong Seong, Hae Young Park, Woon Sup Han, Ju Young Seoh, Soon Nam Lee; Cancer Res Treat. 2003;35(2):109-116. Published online April 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.2.109

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PURPOSE
The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185(HER2)) that has partial homology with the epidermal growth factor receptor (EGFR) and shares intrinsic tyrosine kinase activity. The HER2 gene has been found to be amplified in various human cancers and to be associated with poor prognosis. The authors investigated the correlation between clinicopathologic factors and the overexpression of the p185(HER2) in Korean gastric adenocarcinoma patients, and determined whether the antiproliferative effects of anti- p185(HER2) antibody can also be observed on gastric cancer cell lines that overexpress this growth factor receptor. MATERIALS AND METHODS: We evaluated the relationship between p185(HER2) overexpression and clinicopathological features in 94 (M: F=52: 42) gastric adenocarcinoma patients (median age 59 years). Protein expression was analysed by immunohistochemical staining in paraffin embedded tissues with monoclonal antibody for p185(HER2). To explore the role of humanized anti-p185(HER2) monoclonal antibody trastuzumab (Herceptin ) in vitro, the growth curve of Korean gastric cancer cells that overexpress the p185(HER2) protein was studied and a cell cycle analysis was performed. RESULTS: p185(HER2) overexpression correlates positively with lymph node metastasis (p=0.002), distant metastasis (p=0.01), AJCC classification (p=0.01), higher relapse rate p=0.001), and a tendential association with the pT stage (p=0.054). p185(HER2) overexpression was found to be more frequent in advanced gastric cancer than early gastric cancer (54.1% vs 24.2%, p=0.008). Patients with overexpression of p185(HER2) were found to have significantly lower relapse-free (p=0.003) and overall survival (p= 0.0004) than patients without overexpression. Among several Korean gastric cancer cell lines, SNU-1, SNU-5, and SNU-620 overexpress p185(HER2). Trastuzumab inhibited the proliferation of p185(HER2) overexpressed Korean gastric cancer cell line by 21% with down-regulation of p185(HER2) protein expression. DNA fluorescence flow cytometry of propidium iodide-stained nuclei showed a reduction in the fraction of the S phase following treatment with trastuzumab. CONCLUSIONS: Taken together, our observations suggest the potential prognostic significance of p185(HER2) overexpression in Korean gastric adenocarcinoma patients and point to the need for further research on this mechanism. This suggests the possible use of p185(HER2) as a therapeutic target in gastric cancer.

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