Cancer Research and Treatment

Original Article

The HDAC Inhibitor Entinostat Mediates HER2 Downregulation in Gastric Cancer, Providing the Basis for Its Particular Efficacy in HER2 Amplified Tumors and in Combination Therapies: Tamara Zenz, Robert Jenke, René Thieme, Tim Kahl, Hannes Borchardt, Ines Gockel, Finn K Hansen, Achim Aigner, Thomas RH Büch; Received June 10, 2024 Accepted November 28, 2024 Published online December 10, 2024; DOI: https://doi.org/10.4143/crt.2024.546 [Accepted]

Abstract PDF: Purpose
HER2 inhibition represents a therapeutic approach with proven clinical efficacy in gastric cancer. However, resistance against HER2-directed therapeutics highlights the need for alternative approaches or drug combinations. Histone deacetylase inhibitors (HDACi) display a broad spectrum of antitumor properties, which may include effects on receptor tyrosine kinases.
Materials and Methods
We analyzed the effects of the class I HDACi entinostat in a panel of HER2-amplified and non-amplified gastric adenocarcinoma cells in 2D cell culture as well as in tumor slice models ex vivo and in patient-derived xenografts in vivo. Effects on protein expression / signal transduction were evaluated by immunoblotting and quantitative RT-PCR.
Results
HDAC inhibition reduced HER2 protein expression independently of initial HER2 expression levels. This was associated with the upregulation of the HER2-inhibiting microRNA miR-205. The downregulation of HER2 resulted in reduced AKT phosphorylation, apoptosis induction and antiproliferative effects, with particularly high efficiency in HER2-amplified gastric cancer cells. Inhibiting HER2 by a specific kinase inhibitor in gastric cancer cells with low basal HER2 expression led to HER2 upregulation. This was reversed by entinostat treatment and provided the basis for synergistic cell inhibition upon double treatment.
Conclusion
We describe the downregulation of HER2 in gastric carcinoma cells upon HDACi treatment. Concomitantly, cells with high basal or treatment-induced HER2 expression showed most profound sensitivities towards HDACi. These findings may thus provide the basis for HDACi treatment as a therapeutic option (1) particularly valuable in HER2-amplified gastric cancer and (2) particularly useful in combination therapies with HER2 inhibitors.

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Review Article

The Era of Antibody Drug Conjugates in Lung Cancer: Trick or Threat?: Mariona Riudavets, David Planchard; Received July 26, 2024 Accepted November 27, 2024 Published online November 28, 2024; DOI: https://doi.org/10.4143/crt.2024.714 [Accepted]

Abstract PDF: Antibody Drug Conjugates (ADCs) are a novel class of therapeutics that structurally are composed by an antibody directed to a tumour epitope connected via a linker to a cytotoxic payload, and that have shown significant antitumor activity across a range of malignancies including lung cancer. In this article we review the pharmacology and design of ADCs, as well as we describe the results of different studies evaluating ADCs in lung cancer directed to several targets including HER2, HER3, TROP2, MET, CEACAM5 and DLL3, among others.

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Original Articles

A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2– Locally Advanced Breast Cancer: Integrated Analysis of ¹⁸F-FES PET-CT and Metabolites with Treatment Response: Qing Shao, Ningning Zhang, Xianjun Pan, Wenqi Zhou, Yali Wang, Xiaoliang Chen, Jing Wu, Xiaohua Zeng; Received November 24, 2023 Accepted July 7, 2024 Published online July 9, 2024; DOI: https://doi.org/10.4143/crt.2023.1251 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (¹⁸F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy.
Materials and Methods
Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received ¹⁸F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety.
Results
Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of ¹⁸F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways.
Conclusion
This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. ¹⁸F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

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Gastrointestinal cancer

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 Res Treat. 2024;56(4):1136-1145. Published online April 29, 2024; DOI: https://doi.org/10.4143/crt.2023.1324

Abstract PDF Supplementary Material PubReader ePub

Purpose
Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC).
Materials and Methods
Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity.
Results
RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D.
Conclusion
A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

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Unraveling the future: Innovative design strategies and emerging challenges in HER2-targeted tyrosine kinase inhibitors for cancer therapy
Sixiang Zheng, Ruixian Chen, Lele Zhang, Lun Tan, Lintao Li, Fangyi Long, Ting Wang
European Journal of Medicinal Chemistry.2024; 276: 116702. CrossRef

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Breast cancer

A Nationwide Study on HER2-Low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols: Min Chong Kim, Eun Yoon Cho, So Yeon Park, Hee Jin Lee, Ji Shin Lee, Jee Yeon Kim, Ho-chang Lee, Jin Ye Yoo, Hee Sung Kim, Bomi Kim, Wan Seop Kim, Nari Shin, Young Hee Maeng, Hun Soo Kim, Sun Young Kwon, Chungyeul Kim, Sun-Young Jun, Gui Young Kwon, Hye Jeong Choi, So Mang Lee, Ji Eun Choi, Ae Ri An, Hyun Joo Choi, EunKyung Kim, Ahrong Kim, Ji-Young Kim, Jeong Yun Shim, Gyungyub Gong, Young Kyung Bae; Cancer Res Treat. 2024;56(4):1096-1104. Published online March 6, 2024; DOI: https://doi.org/10.4143/crt.2024.092

Abstract PDF Supplementary Material PubReader ePub

Purpose
Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results.
Materials and Methods
The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected.
Results
Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients.
Conclusion
The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

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Impact of immunohistochemistry staining conditions on the incidence of human epidermal growth factor receptor 2 (HER2)-low breast cancer
Min Chong Kim, Sun Young Kwon, Hye Ra Jung, Young Kyung Bae
Virchows Archiv.2024;[Epub] CrossRef
Breast Cancer: Extracellular Matrix and Microbiome Interactions
Lourdes Herrera-Quintana, Héctor Vázquez-Lorente, Julio Plaza-Diaz
International Journal of Molecular Sciences.2024; 25(13): 7226. CrossRef

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Lung and Thoracic cancer

Comparison of Clinicopathogenomic Features and Treatment Outcomes of EGFR and HER2 Exon 20 Insertion Mutations in Non–Small Cell Lung Cancer: Single-Institution Experience: So Heun Lee, Hyehyun Jeong, Deok Hoon Kim, Se Jin Jang, Sang-We Kim, Shinkyo Yoon, Dae Ho Lee; Cancer Res Treat. 2024;56(3):774-784. Published online January 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1177

Abstract PDF PubReader ePub: Purpose
Exon 20 insertion mutations (E20ins) in epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) in non–small cell lung cancer (NSCLC) patients has become more important with emergence of novel agents targeting E20ins.
Materials and Methods
Advanced/Metastatic NSCLC patients with E20ins were included. EGFR E20ins was identified by two methods, next-generation sequencing (NGS) or real-time polymerase chain reaction (PCR), while HER2 E20ins was done by NGS only.
Results
Between December 2013 and July 2021, E20ins were identified in 107 patients at Asan Medical Center; 67 EGFR E20ins and 40 HER2 E20ins. Out of 32 patients with EGFR E20ins who had tested both PCR and NGS, 17 were identified only through NGS and the other 15 through both tests, giving a discordance rate of 53.1%. There was no clinically significant difference in clinicopathologic features between EGFR and HER2 E20ins; both were observed more frequently in adenocarcinoma, female and never-smokers. Brain metastases were evident at diagnosis in 31.8% of EGFR E20ins and 27.5% of HER2 E20ins, respectively. Platinum-based doublets demonstrated objective response rates (ORR) of 13.3% with a median progression-free survival (PFS) of 4.2 months for EGFR E20ins and 35.3% with 4.7 months for HER2 E20ins, respectively. In contrast, novel EGFR E20ins-targeted agents exhibited an ORR of 46.2% with a median PFS of 5.4 months, while HER2-targeted agents showed an ORR of 50% with that of 7.0 months.
Conclusion
Identification of EGFR and HER2 E20ins is more important as their targeted therapies improved outcomes. Upfront NGS test as a comprehensive molecular approach is strongly warranted.

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Review Article

HER2-Low Breast Cancer: Now and in the Future: Sora Kang, Sung-Bae Kim; Cancer Res Treat. 2024;56(3):700-720. Published online January 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1138

Abstract PDF PubReader ePub: Breast cancer is a heterogeneous disease, and its subtypes are characterized by hormone receptor and human epidermal growth factor receptor 2 (HER2) expression status. “HER2-low” tumors, which exhibit a low level of HER2 expression (immunohistochemistry 1+ or 2+ without gene amplification), were conventionally considered not amenable to anti-HER2 targeting agents based on the results of a phase III trial of trastuzumab. However, this perspective is being challenged by the emergence of novel anti-HER2 antibody-drug conjugates, such as trastuzumab-deruxtecan. These innovative therapies have demonstrated remarkable efficacy against HER2-low breast cancer, shedding new light on a previously overlooked category of breast cancer. Such promising results highlight the need for in-depth investigations of the biology and prognostic implications of HER2-low tumors. In this review, we comprehensively summarize the current evidence surrounding this topic and highlight areas that warrant further exploration and research in the future.

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Original Articles

Breast cancer

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

First-in-Human Phase 1 Study of a B Cell– and Monocyte-Based Immunotherapeutic Vaccine against HER2-Positive Advanced Gastric Cancer: Minkyu Jung, Jii Bum Lee, Hyo Song Kim, Woo Sun Kwon, Hyun Ok Kim, Sinyoung Kim, Myunghwan Park, Wuhyun Kim, Ki-Young Choi, Taegwon Oh, Chang-Yuil Kang, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2024;56(1):208-218. Published online June 28, 2023; DOI: https://doi.org/10.4143/crt.2022.1328

Abstract PDF Supplementary Material PubReader ePub

Purpose
BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer.
Materials and Methods
Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×10⁷ cells/dose), medium (5.0×10⁷ cells/dose), or high dose (1.0×10⁸ cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses.
Results
Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients.
Conclusion
BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.

Citations

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HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments
Magdalena K. Scheck, Ralf D. Hofheinz, Sylvie Lorenzen
Cancers.2024; 16(7): 1336. CrossRef

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GASTric Cancer HER2 Re-Assessment Study 2 (GASTHER2): HER2 Re-assessment for Initially HER2-Negative Advanced Gastric Cancer Patients after Progression on First-Line Treatment: Jaewon Hyung, Hyung-Don Kim, Min-Hee Ryu, Young Soo Park, Meesun Moon, Yoon-Koo Kang; Cancer Res Treat. 2024;56(1):199-207. Published online June 20, 2023; DOI: https://doi.org/10.4143/crt.2023.490

Abstract PDF Supplementary Material PubReader ePub: Purpose
Heterogeneous human epidermal growth factor receptor 2 (HER2) overexpression in gastric cancer may lead to a misdiagnosis of HER2 status. Accurate assessment of HER2 status is essential for optimal treatment as novel HER2-directed agents are being investigated in various clinical settings. We evaluated the usefulness of HER2 re-assessment following progression on first-line treatment in initially HER2-negative advanced gastric cancer (AGC) patients.
Materials and Methods
We enrolled 177 patients with baseline HER2-negative AGC and performed HER2 re-assessment after progression on first-line treatment from February 2012 to June 2016 at Asan Medical Center, Seoul, Korea. The re-assessed HER2 status was analyzed with baseline HER2 status and clinical characteristics.
Results
The median age was 54 years (range, 24 to 80 years), and 123 patients (69.5%) were men. Seven patients (4.0%) were HER2-positive on the re-assessment. Patients with baseline HER2 negativity confirmed by a single test (n=100) had a higher HER2-positive re-assessment rate compared to those who had repeated baseline testing (n=77) (5.0% vs. 2.6%). Among the patients with single baseline HER2 testing, the rate was higher in patients with baseline HER2 immunohistochemistry (IHC) 1+ compared to those with IHC 0 (13.4% vs. 3.6%).
Conclusion
Overall, 4.0% of patients with baseline HER2-negative AGC were HER2-positive on re-assessment, and the HER2-positive re-assessment rate was higher among patients who had a single test at baseline. HER2 re assessment may be considered for initially HER2-negative patients to determine their eligibility for HER2-directed therapy, particularly if their HER2 negativity was determined by a single test, especially if they had a single baseline HER2 IHC 1+ test.

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Breast cancer

Prognostic Value of the Evolution of HER2-Low Expression after Neoadjuvant Chemotherapy: Youzhao Ma, Mingda Zhu, Jingyang Zhang, Minhao Lv, Xiuchun Chen, Zhenzhen Liu; Cancer Res Treat. 2023;55(4):1210-1221. Published online April 4, 2023; DOI: https://doi.org/10.4143/crt.2022.1633

Abstract PDF PubReader ePub

Purpose
Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT).
Materials and Methods
The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined.
Results
Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016).
Conclusion
Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Citations

Citations to this article as recorded by

The Modified Neo-Bioscore System for Staging Breast Cancer Treated with Neoadjuvant Therapy Based on Prognostic Significance of HER2-Low Expression
Yingying Zhao, Xinru Chen, Yaohui Wang, Xueqing Zhang, Jingsong Lu, Wenjin Yin
Journal of Clinical Medicine.2024; 13(7): 1850. CrossRef
Preoperative Differentiation of HER2‐Zero and HER2‐Low from HER2‐Positive Invasive Ductal Breast Cancers Using BI‐RADS MRI Features and Machine Learning Modeling
Jiejie Zhou, Yang Zhang, Haiwei Miao, Ga Young Yoon, Jinhao Wang, Yezhi Lin, Hailing Wang, Yan‐Lin Liu, Jeon‐Hor Chen, Zhifang Pan, Min‐Ying Su, Meihao Wang
Journal of Magnetic Resonance Imaging.2024;[Epub] CrossRef
Comparison of the Pathological Complete Response Rate and Survival Between HER2-Low and HER2-Zero Breast Cancer in Neoadjuvant Chemotherapy Setting: A Systematic Review and Meta-Analysis
Mei Liu, Qin Xiang, Fengsheng Dai, Yixiao Yuan, Zhongjun Wu, Tingxiu Xiang
Clinical Breast Cancer.2024; 24(7): 575. CrossRef
Neoadjuvant chemotherapy efficacy and prognosis in HER2-low and HER2-zero breast cancer patients by HR status: a retrospective study in China
Shaorong Zhao, Yuyun Wang, Angxiao Zhou, Xu Liu, Yi Zhang, Jin Zhang
PeerJ.2024; 12: e17492. CrossRef
Alteration of HER2 Status During Breast Cancer Progression: A Clinicopathological Analysis Focusing on HER2-Low Status
Kyungah Bai, Ji Won Woo, Hyun Jung Kwon, Yul Ri Chung, Koung Jin Suh, Se Hyun Kim, Jee Hyun Kim, So Yeon Park
Laboratory Investigation.2024; 104(8): 102092. CrossRef
HER2-Low Breast Cancer: Now and in the Future
Sora Kang, Sung-Bae Kim
Cancer Research and Treatment.2024; 56(3): 700. CrossRef
Stable or at least once HER2-low status during neoadjuvant chemotherapy confers survival benefit in patients with breast cancer
Yingying Zhao, Xinru Chen, Yaohui Wang, Xueqing Zhang, Yumei Ye, Shuguang Xu, Liheng Zhou, Yanping Lin, Jingsong Lu, Wenjin Yin
Annals of Medicine.2024;[Epub] CrossRef
The prognostic impact of Her2 status in early triple negative breast cancer: a Turkish Oncology Group (TOG) study
Neslihan Özyurt, Ali Alkan, Burcu Gülbağcı, Mustafa Seyyar, Esra Aydın, Mustafa Şahbazlar, Mehmet Türker, Oğuzcan Kınıkoğlu, Tahir Yerlikaya, Gülhan Dinç, Ali Aytaç, Ziya Kalkan, Senar Ebinç, İlkay Gültürk, Merve Keskinkılıç, Zehra Sucuoğlu İşleyen, Dilek
Scientific Reports.2024;[Epub] CrossRef
Prognostic implications of HER2 changes after neoadjuvant chemotherapy in patients with HER2-zero and HER2-low breast cancer
Sora Kang, So Heun Lee, Hee Jin Lee, Hyehyun Jeong, Jae Ho Jeong, Jeong Eun Kim, Jin-Hee Ahn, Kyung Hae Jung, Gyungyub Gong, Hak Hee Kim, Saebyeol Lee, Jongwon Lee, Sung-Bae Kim
European Journal of Cancer.2023; : 112956. CrossRef

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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

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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
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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
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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

5,312 View
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8 Crossref

Breast cancer

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 Res Treat. 2023;55(2):531-541. Published online September 7, 2022; DOI: https://doi.org/10.4143/crt.2022.221

Abstract PDF Supplementary Material PubReader ePub

Purpose
Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer.
Materials and Methods
We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment.
Results
Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors.
Conclusion
Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

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Safety and efficacy of pyrotinib for HER‑2‑positive breast cancer in the neoadjuvant setting: A systematic review and meta‑analysis
Qian Ma, Bai Wei, Bi-Cheng Wang, Ganxin Wang, Xuan Zhou, Yan Wang
Oncology Letters.2024;[Epub] CrossRef
A novel PIK3CA hot-spot mutation in breast cancer patients detected by HRM-COLD-PCR analysis
Saoussen Debouki-Joudi, Wala Ben Kridis, Fatma Trifa, Wajdi Ayadi, Abdelmajid Khabir, Tahia Sellami-Boudawara, Jamel Daoud, Afef Khanfir, Raja Mokdad-Gargouri
Breast Disease.2024; 43(1): 213. CrossRef
Liquid Biopsy in the Clinical Management of Cancers
Ho-Yin Ho, Kei-See (Kasey) Chung, Chau-Ming Kan, Sze-Chuen (Cesar) Wong
International Journal of Molecular Sciences.2024; 25(16): 8594. CrossRef
Modeling the management of patients with human epidermal growth factor receptor 2-positive breast cancer with liquid biopsy: the future of precision medicine
Eleonora Nicolò, Caterina Gianni, Giuseppe Curigliano, Carolina Reduzzi, Massimo Cristofanilli
Current Opinion in Oncology.2024; 36(6): 503. CrossRef
Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer
Li Yin, Gui-lai Chen, Zhuo Xiang, Yu-lin Liu, Xing-yu Li, Jing-wang Bi, Qiang Wang
Biomedicine & Pharmacotherapy.2023; 162: 114648. CrossRef
Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
Scientific Reports.2023;[Epub] 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
Appraisal of Systemic Treatment Strategies in Early HER2-Positive Breast Cancer—A Literature Review
Danilo Giffoni de Mello Morais Mata, Rania Chehade, Malek B. Hannouf, Jacques Raphael, Phillip Blanchette, Abdullah Al-Humiqani, Monali Ray
Cancers.2023; 15(17): 4336. CrossRef
The clinical significance of HER2 expression in DCIS
Ioanna Akrida, Francesk Mulita
Medical Oncology.2022;[Epub] CrossRef

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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.

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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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305 Download
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Real World Evidence of Neoadjuvant Docetaxel/Carboplatin/Trastuzumab/Pertuzumab (TCHP) in Patients with HER2-Positive Early or Locally Advanced Breast Cancer: A Single-Institutional Clinical Experience: Ji-Yeon Kim, Seok Jin Nam, Jeong Eon Lee, Jonghan Yu, Byung Joo Chae, Se Kyung Lee, Jai Min Ryu, Jin Seok Ahn, Young-Hyuck Im, Seok Won Kim, Yeon Hee Park; Cancer Res Treat. 2022;54(4):1091-1098. Published online January 10, 2022; DOI: https://doi.org/10.4143/crt.2021.901

Abstract PDF Supplementary Material PubReader ePub

Purpose
Docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) regimen is frequently used to treat early and locally advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC) in neoadjuvant setting. However, large-scaled real-world evidence did not exist.
Materials and Methods
We retrospectively reviewed medical records of patients with early or locally advanced HER2-positive BC who underwent neoadjuvant TCHP followed by curative surgery at Samsung Medical Center between January 2016 and August 2020.
Results
Of 447 patients, 316 (70.7%) received breast-conserving surgery and 131 (29.3%) received total mastectomy. In terms of neoadjuvant chemotherapy response, pathologic complete response (pCR) and residual cancer burden (RCB) score were analyzed. The rate of pCR was 64% a class of RCB 0 was observed in 65% of cases, RCB class I in 12%, RCB class II in 14%, and RCB class III in 2%. The 3-year event-free survival rate was 90.6%, BC with pCR occurred in 92.8%, and BC with non-pCR in 86.3% (p=0.016). In terms of distant metastasis, the 3-year distant recurrence-free survival rate was 93.5%; BC with pCR occurred in 95.9% and BC with non-pCR in 89.2% (p=0.013). Mucositis (85.2%), pain (83.2%), and diarrhea (70.5%) were the most common non-hematologic adverse events. In terms of hematologic adverse events, anemia (89.9%) was the most commonly observed adverse events followed by thrombocytopenia (29.8%).
Conclusion
Neoadjuvant TCHP therapy had a pCR rate of 64% and a 3-year event-free survival of 90% in real world experience. In terms of toxicity profile, anemia was frequently observed and adequate management including occasional transfusion was required.

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De-escalation of neoadjuvant taxane and carboplatin therapy in HER2-positive breast cancer with dual HER2 blockade: a multicenter real-world experience in China
Song Wu, Li Bian, Haibo Wang, Shaohua Zhang, Tao Wang, Zhigang Yu, Jianbin Li, Feng Li, Kun Wang, Zefei Jiang
World Journal of Surgical Oncology.2024;[Epub] CrossRef
Distinct ER and PR expression patterns significantly affect the clinical outcomes of early HER2-positive breast cancer: A real-world analysis of 871 patients treated with neoadjuvant therapy
Haizhu Chen, Xiujuan Gui, Ziwei Zhou, Fengxi Su, Chang Gong, Shunrong Li, Wei Wu, Nanyan Rao, Qiang Liu, Herui Yao
The Breast.2024; 75: 103733. CrossRef
Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study
Ahmet Bilici, Omer Fatih Olmez, Muhammed Ali Kaplan, Berna Oksuzoglu, Ahmet Sezer, Nuri Karadurmus, Erdem Cubukcu, Mehmet Ali Nahit Sendur, Sercan Aksoy, Dilek Erdem, Gul Basaran, Burcu Cakar, Abdallah T. M. Shbair, Cagatay Arslan, Ahmet Taner Sumbul, Sem
Acta Oncologica.2023; 62(4): 381. CrossRef
Pathologic Complete Response Achieved in Early-Stage HER2-Positive Breast Cancer After Neoadjuvant Therapy With Trastuzumab and Chemotherapy vs. Trastuzumab, Chemotherapy, and Pertuzumab: A Systematic Review and Meta-Analysis of Clinical Trials
Faizan Fazal, Muhammad Nauman Bashir, Maham Leeza Adil, Usama Tanveer, Mansoor Ahmed, Taha Zahid Chaudhry, Ali Ahmad Ijaz, Muhammad Haider
Cureus.2023;[Epub] CrossRef
Trends of axillary surgery in breast cancer patients with axillary lymph node metastasis: a comprehensive single-center retrospective study
Yeon Jin Kim, Hye Jin Kim, Soo Yeon Chung, Se Kyung Lee, Byung Joo Chae, Jonghan Yu, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Jai Min Ryu
Annals of Surgical Treatment and Research.2023; 105(1): 10. CrossRef
Anthracyclines versus No Anthracyclines in the Neoadjuvant Strategy for HER2+ Breast Cancer: Real-World Evidence
Inês Soares de Pinho, Paulo Luz, Lucy Alves, Raquel Lopes-Brás, Vanessa Patel, Miguel Esperança-Martins, Lisa Gonçalves, Ritas Freitas, Diana Simão, Maria Roldán Galnares, Isabel Fernandes, Silvia Artacho Criado, Salvador Gamez Casado, Jose Baena Cañada,
Clinical Drug Investigation.2023; 43(9): 691. CrossRef
Benefit of postoperative regional nodal irradiation in patients receiving preoperative systemic therapy with docetaxel/carboplatin/trastuzumab/pertuzumab for HER2-positive breast cancer
Nalee Kim, Ji-Yeon Kim, Won Park, Won Kyung Cho, Tae Gyu Kim, Young-Hyuck Im, Jin Seok Ahn, Jeong Eon Lee, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung Joo Chae, Sei Kyung Lee, Jai-Min Ryu, Yeon Hee Park, Haeyoung Kim
The Breast.2023; 72: 103594. CrossRef
Response Rate and Safety of a Neoadjuvant Pertuzumab, Atezolizumab, Docetaxel, and Trastuzumab Regimen for Patients With ERBB2-Positive Stage II/III Breast Cancer
Hee Kyung Ahn, Sung Hoon Sim, Koung Jin Suh, Min Hwan Kim, Jae Ho Jeong, Ji-Yeon Kim, Dae-Won Lee, Jin-Hee Ahn, Heejung Chae, Kyung-Hun Lee, Jee Hyun Kim, Keun Seok Lee, Joo Hyuk Sohn, Yoon-La Choi, Seock-Ah Im, Kyung Hae Jung, Yeon Hee Park
JAMA Oncology.2022; 8(9): 1271. CrossRef

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Clinical Significance of Major Angiogenesis-Related Effectors in Patients with Metastatic Breast Cancer Treated with Trastuzumab-Based Regimens: Helen P. Kourea, Foteinos-Ioannis Dimitrakopoulos, Georgia-Angeliki Koliou, Anna Batistatou, Kyriaki Papadopoulou, Mattheos Bobos, Anthoula Asimaki-Vlachopoulou, Sofia Chrisafi, Kitty Pavlakis, Kyriakos Chatzopoulos, Eleni Galani, George Pentheroudakis, Dimitrios Pectasides, Dimitrios Bafaloukos, Eleni Res, Pavlos Papakostas, Angelos Koutras, Vassiliki Kotoula, George Fountzilas; Cancer Res Treat. 2022;54(4):1053-1064. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.748

Abstract PDF Supplementary Material PubReader ePub

Purpose
Angiogenesis is a crucial phenomenon in the development and progression of breast cancer (BC), but the clinical significance of angiogenesis-related proteins in metastatic BC remains unknown. This study investigates the prognostic value of vascular endothelial growth factor receptors 1, 2, 3 (VEGFR1, VEGFR2, VEGFR3) as well as vascular endothelial growth factors A and C (VEGFA and VEGFC) in metastatic BC patients treated with trastuzumab-based regimens.
Materials and Methods
Two hundred female patients were included. Protein and mRNA expression of the studied angiogenesis-related factors were evaluated by immunohistochemistry and quantitative polymerase chain reaction, respectively.
Results
High expression of VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 in the tumor cells was observed in 43.5%, 24.2%, 36%, 29.5%, and 43%, respectively. Stromal elements expressed high levels of VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 in 78.9%, 93.3%, 90.7%, 90.2%, and 74.8% of tumors with available data. High tumor cell expression of VEGFR1 was a favorable prognosticator for survival among patients with human epidermal growth factor receptor 2 (HER2)–positive tumors (hazard ratio [HR], 0.55; p=0.013). A trend towards longer progression-free survival was detected univariately for patients with HER2-negative tumors and high expression of VEGFR2 (HR, 0.60; p=0.059).
Conclusion
VEGFR1 and VEGFR2 seem to have significant prognostic value in BC patients with metastatic disease treated with trastuzumab-based regimens.

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Apatinib beyond first progression is associated with prolonged overall survival in patients with advanced breast cancer: Results from an observational study
Jing Wang, Jinghao Jia, Jingjing Liu, Xuemin Yao, Zhiyong Yuan
Experimental and Therapeutic Medicine.2024;[Epub] CrossRef

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109 Download
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1 Crossref

Breast Cancer

Talazoparib Versus Chemotherapy in Patients with HER2-negative Advanced Breast Cancer and a Germline BRCA1/2 Mutation Enrolled in Asian Countries: Exploratory Subgroup Analysis of the Phase III EMBRACA Trial: Kyung-Hun Lee, Joohyuk Sohn, Annabel Goodwin, Tiziana Usari, Silvana Lanzalone, Seock-Ah Im, Sung-Bae Kim; Cancer Res Treat. 2021;53(4):1084-1095. Published online March 24, 2021; DOI: https://doi.org/10.4143/crt.2020.1381

Abstract PDF Supplementary Material PubReader ePub

Purpose
We evaluated study outcomes in patients enrolled in Asian regions in the phase III EMBRACA trial of talazoparib vs. chemotherapy.
Materials and Methods
Patients with human epidermal growth factor receptor 2–negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician’s choice). Primary endpoint was progression-free survival (PFS) per independent central review in the intent-to-treat (ITT) population. This post-hoc analysis evaluated efficacy/safety endpoints in the ITT population of patients enrolled in Asian regions.
Results
Thirty-three patients were enrolled at Asian sites (talazoparib, n=23; chemotherapy, n=10). Baseline characteristics were generally comparable with the overall EMBRACA population. In Asian patients, median PFS was 9.0 months (95% confidence interval [CI] 3.0, 15.2) for talazoparib and 7.1 months (95% CI, 1.2, not reached) for chemotherapy (hazard ratio [HR] 0.74 [95% CI, 0.22, 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy (62.5% [95% CI, 35.4, 84.8] vs. 25.0% [95% CI, 3.2, 65.1]). Median overall survival was 20.7 months (95% CI, 9.4, 40.1) versus 21.2 months (95% CI, 2.7, 35.0) months (HR, 1.41 [95% CI, 0.49, 4.05]). In Asian patients, fewer grade 3/4 adverse events (AEs), serious AEs (SAEs), grade 3/4 SAEs, and AEs resulting in dose reduction/discontinuation occurred with talazoparib than chemotherapy; for talazoparib, the frequency of these events was lower in Asian patients versus overall EMBRACA population.
Conclusion
In this subgroup analysis, talazoparib numerically improved efficacy versus chemotherapy and was generally well tolerated in Asian patients, with fewer grade 3/4 TEAEs, SAEs, and TEAEs leading to dose modification vs. the overall EMBRACA population.

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HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis
Pu-Chun Li, Yi-Fan Zhu, Jia-Ni Pan, Qiao-Yan Zhu, Yu-Yang Liao, Xiao-Wen Ding, Lin-Feng Zheng, Wen-Ming Cao
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Detection and analysis of the safety profile of talazoparib based on FAERS database
Mufei Tang, Peiyan Liu, Linzhe Du, Yuanyuan Li, Jinjin Chen, Yang Li
Expert Opinion on Drug Safety.2024; : 1. CrossRef
Facing inevitable PARPis resistance: Mechanisms and therapeutic strategies for breast cancer treatment
Haixia Liu, Xiaohui Chen, Yimin Jia, Hengyi Chen, Xiaohui Wang, Guoxiang Liu, Yang Luo
Interdisciplinary Medicine.2023;[Epub] CrossRef
Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer
Shicheng Yang, Allen Green, Needa Brown, Alexis Robinson, Merline Senat, Bryanna Testino, Daniela M. Dinulescu, Srinivas Sridhar
Frontiers in Oncology.2023;[Epub] CrossRef
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer
S.-A. Im, A. Gennari, Y.H. Park, J.H. Kim, Z.-F. Jiang, S. Gupta, T.H. Fadjari, K. Tamura, M.Y. Mastura, M.L.T. Abesamis-Tiambeng, E.H. Lim, C.-H. Lin, A. Sookprasert, N. Parinyanitikul, L.-M. Tseng, S.-C. Lee, P. Caguioa, M. Singh, Y. Naito, R.A. Hukom,
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Zhiying Zhang, Rui Zhang, Donghai Li
Biologics: Targets and Therapy.2023; Volume 17: 113. CrossRef
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Evthokia A. Hobbs, Jennifer K. Litton, Timothy A. Yap
Expert Opinion on Pharmacotherapy.2021; : 1. CrossRef

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Breast cancer

Real-World Data of Pyrotinib-Based Therapy in Metastatic HER2-Positive Breast Cancer: Promising Efficacy in Lapatinib-Treated Patients and in Brain Metastasis: Ying Lin, Mingxi Lin, Jian Zhang, Biyun Wang, Zhonghua Tao, Yiqun Du, Sheng Zhang, Jun Cao, Leiping Wang, Xichun Hu; Cancer Res Treat. 2020;52(4):1059-1066. Published online April 24, 2020; DOI: https://doi.org/10.4143/crt.2019.633

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis.
Materials and Methods
One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included.
Results
Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea.
Conclusion
Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.

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Dagmara Buczek, Renata Zaucha, Jacek Jassem
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Comparison of the prognostic effect of pyrotinib plus trastuzumab and chemotherapy different lines therapy in HER2-positive advanced breast cancer
Yangqingqing Zhou, Hui Wang, Jiao Yang, Fan Wang, Danfeng Dong, Xiaoai Zhao, Le Wang, Ruiyuan He, Zhiping Ruan, Jin Yang
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Min-long Chen, Wenjie Yu, Binbin Cui, Yijian Yu, Zhaosheng Ma
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Efficacy and safety of inetetamab-containing regimens in patients with HER2-positive metastatic breast cancer: a real-world retrospective study in China
Xiaoyu Liu, Peng Zhang, Chao Li, Xiang Song, Zhaoyun Liu, Wenna Shao, Sumei Li, Xinzhao Wang, Zhiyong Yu
Frontiers in Oncology.2023;[Epub] CrossRef
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Matthew N. Mills, Whitney King, Aixa Soyano, Yolanda Pina, Brian J. Czerniecki, Peter A. Forsyth, Hatem Soliman, Hyo S. Han, Kamran A. Ahmed
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Chengcheng Gong, Cheng Liu, Zhonghua Tao, Jian Zhang, Leiping Wang, Jun Cao, Yannan Zhao, Yizhao Xie, Xichun Hu, Zhongyi Yang, Biyun Wang
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Yuwen Bao, Zhuolin Zhang, Xuan He, Lele Cai, Xiao Wang, Xin Li
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Mohammed Kaleem, Mahmood Hassan Dalhat, Lubna Azmi, Turky Omar Asar, Wasim Ahmad, Maimonah Alghanmi, Amal Almostadi, Torki A. Zughaibi, Shams Tabrez
International Journal of Molecular Sciences.2022; 23(19): 11687. CrossRef
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Jing Liu, Xianglu Sun, Qianyu Du, Jinghao Yao, Mengfen Dai, Qianqian Cheng, Han Xu, Yawei Li, Xiuli Liu, Mingliang Zhang, Yongchun Zhou, Yan Yang
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Renaud Sabatier, Johan Martin, Cécile Vicier, Mathilde Guérin, Audrey Monneur, Magali Provansal, Louis Tassy, Carole Tarpin, Jean-Marc Extra, Frédéric Viret, Anthony Goncalves
Journal of Clinical Medicine.2021; 10(6): 1272. CrossRef
Pyrotinib Combined With Vinorelbine in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study
Yi Li, Yixuan Qiu, Huihui Li, Ting Luo, Wei Li, Hong Wang, Bin Shao, Biyun Wang, Rui Ge
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Yueyue Liu, Qian Zhang, Chao Lu, Wei Hu
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Alejandro Garcia-Alvarez, Andri Papakonstantinou, Mafalda Oliveira
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Yizhao Xie, Yi Li, Luo Ting, Die Sang, Peng Yuan, Wei Li, Huihui Li, Rui Ge, Biyun Wang
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D. J Ouyang, Q. T Chen, M. Anwar, N. Xie, Q. C. Ouyang, P. Z. Fan, L. Y. Qian, G. N. Chen, E. X. Zhou, L. Guo, X. W. Gu, B. N. Ding, X. H. Yang, L. P. Liu, C. Deng, Z. Xiao, J. Li, Y. Q. Wang, S. Zeng, Shouman Wang, Wenjun Yi
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Akanksha Sharma, Lauren Singer, Priya Kumthekar
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16 Crossref

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
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Case Report

Effective Treatment of Solitary Pituitary Metastasis with Panhypopituitarism in HER2-Positive Breast Cancer by Lapatinib: Youngmok Park, Hyemin Kim, Eui-Hyun Kim, Chang-Ok Suh, Soohyeon Lee; Cancer Res Treat. 2016;48(1):403-408. Published online February 16, 2015; DOI: https://doi.org/10.4143/crt.2014.165

Abstract PDF PubReader ePub

Brain metastasis affects one third of patients with HER2-positive breast cancer after treatment with trastuzumab. Surgical resection and radiation therapy are often unsuccessful at accomplishing complete control of metastasis. Lapatinib is presumed to cross the blood-brain barrier, and exhibits clinical activities for treatment of HER2- positive breast cancer. A 43-year-old woman was treated for early breast carcinoma with total mastectomy, axillary lymph-node dissection, and adjuvant chemotherapy with cyclophosphamide plus doxorubicin. After the end of adjuvant trastuzumab therapy, she was diagnosed with panhypopituitarism due to pituitary metastasis. Surgical removal and whole brain radiation therapy were performed, but a portion of viable tumor remained. Only taking lapatinib, the size of the metastatic lesion began to shrink. Trastuzumab may have controlled the micro-metastasis of breast cancer, but it was unable to control its progression to the central nervous system. Lapatinib is a possible option for HER2-positive metastatic breast cancer patients with brain metastasis.

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Hajrullah Ahmeti, Eva Jüttner, Christoph Röcken, Olav Jansen, Matthias Laudes, Michael Synowitz
Journal of Neurological Surgery Part A: Central European Neurosurgery.2023; 84(03): 295. CrossRef
Endonasal endoscopic approach for sellar metastatic pathologies: a national observation
Gokmen Kahilogullari, Eyup Bayatli, Murat Geyik, Burak Cabuk, Suha Beton, Omur Gunaldi, Osman Tanrıverdi, Nuri Eralp Cetinalp, Ozgur Tarkan, Ali Erdem Yıldırım, Yahya Efe Guner, Ali Nehir, Ethem Goksu, Mahmut Akyuz, İlkay Isikay, Bulent Duz, Emrah Celtikc
British Journal of Neurosurgery.2023; 37(2): 206. CrossRef
Pituitary metastases: a case series and scoping review
Kaiyun Yang, Sabrina L. Begley, Daniel Lynch, Vincent Ye, Jasleen Saini, Enrique Gutierrez, Jaclyn Vialet, Barbara-Ann Millar, Tatianna Conrad, Normand Laperriere, Mark Bernstein, Gelareh Zadeh, David B. Shultz, Paul N. Kongkham
Pituitary.2023; 26(5): 538. CrossRef
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Neilen P Rasiah, Abdulrahman Albakr, Suzanne Kosteniuk, Yves Starreveld
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Xiaohai Liu, Renzhi Wang, Mingchu Li, Ge Chen
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Sellar Metastases
Mostafa Shahein, Thiago Albonette-Felicio, Ricardo L. Carrau, Daniel M. Prevedello
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World Neurosurgery.2019; 124: 445. CrossRef
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Yi Zhao, Wei Lian, Bing Xing, Ming Feng, Xiaohai Liu, Renzhi Wang, Weixun Zhou
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Capecitabine/lapatinib/paclitaxel

Reactions Weekly.2016; 1596(1): 49. CrossRef
Unexpected Single Crystal Growth Induced by a Wire and New Crystalline Structures of Lapatinib
Gabriel L. B. de Araujo, Matthias Zeller, Daniel Smith, Haichen Nie, Stephen R. Byrn
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Original Articles

Prognostic Role of Interleukin-6, Interleukin-8, and Leptin Levels According to Breast Cancer Subtype: Young Ae Cho, Mi-Kyung Sung, Jee-Young Yeon, Jungsil Ro, Jeongseon Kim; Cancer Res Treat. 2013;45(3):210-219. Published online September 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.3.210

Abstract PDF PubReader ePub

PURPOSE
Inflammation within the tumor microenvironment has been reported to show an association with poor prognosis in breast cancer. However, the associations may differ according to breast cancer subtype. In this study, we investigated the association between inflammation-related markers and breast cancer recurrence according to patients' tumor subtypes.
MATERIALS AND METHODS
This prospective study included 240 patients who underwent surgery for management of newly diagnosed breast cancer. Levels of inflammation-related markers (interleukin [IL]-1beta, IL-6, IL-8, monocyte chemoattractant protein-1 [MCP-1], leptin, and adiponectin) were measured at diagnosis, and the associations between these markers and breast cancer recurrence during a six-year follow-up period were examined using the Kaplan-Meier statistical method.
RESULTS
Overall, inflammation-related markers showed no association with breast cancer recurrence. However, when data were stratified by tumor subtype, higher levels of some mediators showed an association with poor prognosis among patients with particular subtypes. Compared to patients without recurrence, patients with recurrence had higher levels of circulating IL-6 (p=0.024) and IL-8 (p=0.016) only among those with HER2- tumors and had higher levels of leptin (p=0.034) only among those with estrogen receptor (ER)+/progesterone receptor (PR)+ tumors. Results of survival analyses revealed an association of high levels of IL-6 (p=0.016) and IL-8 (p=0.022) with poor recurrence-free survival in patients with HER2- tumors. In addition, higher leptin levels indicated shorter recurrence-free survival time only among patients with ER+/PR+ tumors (p=0.022).
CONCLUSION
We found that certain cytokines could have a differential prognostic impact on breast cancer recurrence according to breast cancer subtype. Conduct of additional large studies will be required in order to elucidate the precise roles of these cytokines in breast cancer progression.

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Correlation of AR, EGFR, and HER2 Expression Levels in Prostate Cancer: Immunohistochemical Analysis and Chromogenic In Situ Hybridization: Kwang Hyun Baek, Min Eui Hong, Yoon Yang Jung, Chung Hun Lee, Tae Jin Lee, Eon Sub Park, Mi Kyung Kim, Jae Hyung Yoo, Soo Whan Lee; Cancer Res Treat. 2012;44(1):50-56. Published online March 31, 2012; DOI: https://doi.org/10.4143/crt.2012.44.1.50

Abstract PDF PubReader ePub

PURPOSE
The androgen receptor (AR) plays a central role in prostate cancer. Evidence from several groups indicates that epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) may enhance AR activity in prostate cancer cell lines. This study was designed to investigate the protein expression of AR, EGFR, and HER2 and to determine whether the EGFR and HER2 genes are amplified in prostate cancer tissues.
MATERIALS AND METHODS
The protein expression levels of AR, EGFR, and HER2 in a tissue microarray block of 66 prostate cancer samples were investigated by immunohistochemical analysis and chromogenic in situ hybridization was used to determine whether the EGFR and HER2 genes were amplified in these tissues.
RESULTS
The AR and EGFR proteins were expressed in 59.1% and 40.9% of prostate cancers, respectively, but their expression levels were not significantly associated with clinicopathologic factors. Of the cases in which tissues were negative for EGFR protein expression, 69.2% were positive for AR protein expression; however, AR protein expression was significantly reduced (44.4%) in tissues in which EGFR protein was expressed. HER2 expression was detected in only 1 case (1.5%). No amplification of the EGFR or HER2 genes was found in prostate cancer specimens.
CONCLUSION
This study was limited by small number of subjects, but it can still be inferred that the expression levels of the AR and EGFR proteins are inversely correlated in prostate cancer patients. The potential utility of EGFR and HER2 as prognostic factors or therapeutic targets warrants further study.

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Implications of Bone-Only Metastases in Breast Cancer: Favorable Preference with Excellent Outcomes of Hormone Receptor Positive Breast Cancer: Su Jin Lee, Silvia Park, Hee Kyung Ahn, Jun Ho Yi, Eun Yoon Cho, Jong Mu Sun, Jeong Eon Lee, Seok Jin Nam, Jung-Hyun Yang, Yeon Hee Park, Jin Seok Ahn, Young-Hyuck Im; Cancer Res Treat. 2011;43(2):89-95. Published online June 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.2.89

Abstract PDF PubReader ePub

PURPOSE
The aim of the current study was to determine the incidence, clinical presentation, and treatment outcomes of "bone-only metastases" in patients with breast cancer and to analyze the impact of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status on prognosis.
MATERIALS AND METHODS
Between 1994 and 2007, of 968 patients with metastatic breast cancer who underwent palliative management at Samsung Medical Center, 565 (57%) relapsed with distant metastases. Of the 968, 146 (15%) had bone-only metastases during a median follow-up period of 75 months. Among the 146 patients with bone-only metastases, 122 (84%) were relapsed patients after curative surgery and 24 (26%) were initially metastatic cases.
RESULTS
The median time from primary surgery to bone-only metastases of the 122 patients was 37 months (95% confidence interval [CI], 27 to 46 months). Bone-only metastases were more common in the HR-positive group than in the other subtypes (85% for HR+; 8.2% for HER2+; 6.8% for triple negative. Among all 146 patients, 75 (51%) were treated with hormone therapy. The median post-relapse progression-free survival was 15 months (95%CI, 13 to 17 months). The median overall survival was much longer in the HR+ patients than the HER2+ and triple negative breast cancer patients with marginal statistical significance (65 vs. 40 vs. 40 months, p=0.077).
CONCLUSION
Breast cancer patients with "bone-only metastases" had excellent clinical outcomes. Further study is now warranted to reveal the underlying biology that regulates the behavior of this indolent tumor, as it should identify 'favorable tumor characteristics' in addition to 'favorable preferential metastatic site.'

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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.

Citations

Citations to this article as recorded by

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
Oncotarget.2016; 7(39): 63571. CrossRef
Serum HER2 levels are increased in cats with mammary carcinomas and predict tissue HER2 status
Maria Soares, Rita Ribeiro, Shabir Najmudin, Andreia Gameiro, Rita Rodrigues, Fátima Cardoso, Fernando Ferreira
Oncotarget.2016; 7(14): 17314. CrossRef
A comparative study of disease genes and drug targets in the human protein interactome
Jingchun Sun, Kevin Zhu, W Jim Zheng, Hua Xu
BMC Bioinformatics.2015;[Epub] CrossRef
Classification of Cancer Primary Sites Using Machine Learning and Somatic Mutations
Yukun Chen, Jingchun Sun, Liang-Chin Huang, Hua Xu, Zhongming Zhao
BioMed Research International.2015; 2015: 1. CrossRef
HER2/CEP17 ratio and HER2 immunohistochemistry predict clinical outcome after first-line trastuzumab plus taxane chemotherapy in patients with HER2 fluorescence in situ hybridization-positive metastatic breast cancer
Ji-Won Kim, Jee Hyun Kim, Seock-Ah Im, Yu Jung Kim, Hye-Suk Han, Jin-Soo Kim, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Yoon Kyung Jeon, Do-Youn Oh, Tae-You Kim, In Ae Park
Cancer Chemotherapy and Pharmacology.2013; 72(1): 109. CrossRef
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
Cancer Chemotherapy and Pharmacology.2013; 72(5): 1023. CrossRef
ABCB1, FCGR2A, and FCGR3A Polymorphisms in Patients with HER2-Positive Metastatic Breast Cancer Who Were Treated with First-Line Taxane plus Trastuzumab Chemotherapy
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
Oncology.2012; 83(4): 218. CrossRef
In vivo activity of novel anti-ErbB2 antibody chA21 alone and with Paclitaxel or Trastuzumab in breast and ovarian cancer xenograft models
Guodong Shen, Hui Huang, Anli Zhang, Ting Zhao, Siyi Hu, Liansheng Cheng, Jing Liu, Weihua Xiao, Bin Ling, Qiang Wu, Lihua Song, Wei Wei
Cancer Immunology, Immunotherapy.2011; 60(3): 339. CrossRef
Serum HER2 Level Measured by Dot Blot: A Valid and Inexpensive Assay for Monitoring Breast Cancer Progression
Li-Duan Tan, Yuan-Yuan Xu, Yue Yu, Xiao-Qing Li, Ying Chen, Yu-Mei Feng, Irina Lebedeva
PLoS ONE.2011; 6(4): e18764. CrossRef

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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

Abstract PDF

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.

Citations

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A case of pathological complete regression in combined modality treatment of resectable Her2/neu-positive gastric cancer
A. V. Avgustinovich, S. G. Afanasyev, L. V. Spirina, E. V. Kaygorodova, R. V. Ermolenko, E. N. Samtsov, I. G. Frolova, O. V. Cheremisina
Siberian journal of oncology.2024; 23(1): 170. CrossRef
The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer
Feng‐Hua Wang, Lin Shen, Jin Li, Zhi‐Wei Zhou, Han Liang, Xiao‐Tian Zhang, Lei Tang, Yan Xin, Jing Jin, Yu‐Jing Zhang, Xiang‐Lin Yuan, Tian‐Shu Liu, Guo‐Xin Li, Qi Wu, Hui‐Mian Xu, Jia‐Fu Ji, Yuan‐Fang Li, Xin Wang, Shan Yu, Hao Liu, Wen‐Long Guan, Rui‐Hu
Cancer Communications.2019; 39(1): 1. CrossRef
The neutrophil-to-lymphocyte ratio prechemotherapy and postchemotherapy as a prognostic marker in metastatic gastric cancer
Hyunho Kim, Sang Mi Ro, Ji Hyun Yang, Joon Won Jeong, Ji Eun Lee, Sang Young Roh, In-Ho Kim
The Korean Journal of Internal Medicine.2018; 33(5): 990. CrossRef
Potential Prognostic Significance of p185HER2 Overexpression with Loss of PTEN Expression in Gastric Carcinomas
Seock-Ah lm, Kyung Eun Lee, Eunmi Nam, Do Yeun Kim, Joo-Ho Lee, Ho-Seong Han, Ju-Young Seoh, Hae-Young Park, Min-Sun Cho, Woon Sup Han, Soon Nam Lee
Tumori Journal.2005; 91(6): 513. CrossRef

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