Cancer Research and Treatment

Original Article

Pilot Study for Feasibility of Onco-Geriatric Intervention Model in Older Patients with Cancer in a Tertiary Academic Hospital: Jin Won Kim, Jung-Yeon Choi, Woochan Park, Minsu Kang, Jeongmin Seo, Eun Hee Jung, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Sang-A Kim, Ji Yun Lee, Jeong-Ok Lee, Soo-Mee Bang, Kwang-il Kim, Jee Hyun Kim; Received January 20, 2025 Accepted March 11, 2025 Published online March 12, 2025; DOI: https://doi.org/10.4143/crt.2025.079 [Accepted]

Abstract PDF: Purpose
Older cancer patients face unique challenges due to age-related physiological changes, increasing their vulnerability to treatment-related toxicities. Geriatric assessment (GA) is a validated tool for optimizing care, yet there is no consensus on integrating geriatric interventions into oncology. This study evaluates the feasibility of a tailored onco-geriatric intervention model incorporating the KG-7 screening tool.
Materials and Methods
This prospective study included 30 patients aged ≥70 years with solid tumors undergoing adjuvant or palliative chemotherapy. Patients scoring ≤5 of KG-7 were eligible. Tailored interventions incorporating KG-7 included polypharmacy, functional status, mobility, nutrition, cognition, emotional well-being, insomnia, social support, and medical problem. KG-7, GA, and quality of life (QoL) were followed at 12 weeks.
Results
Participants (median age: 79.5 years) had colon (43.3%), pancreatic (23.3%), or gastric cancer (23.3%). At baseline, most patients showed independent ADL (100%)/IALD (90%). However, 93.3% had abnormal GA. Particularly, 86.7% were either malnourished or at risk of malnutrition. The most frequently identified intervention needs included polypharmacy (70.0%), nutritional support (60.0%), and emotional well-being (50.0%) with high adherence (100.0%, 88.9%, and 46.7%, respectively). At 12 weeks, KG-7 scores improved in 43.8% of patients, and 69.2% of GA domains were improved. QoL analysis revealed modest improvement in Global Health Status (mean difference 6.3, p=0.176). One-year survival rates were 92.3% and 79.4% for adjuvant and palliative groups, respectively.
Conclusion
The onco-geriatric intervention model incorporating KG-7 demonstrated high feasibility and potential to enhance clinical outcomes. Future studies should validate this approach in randomized trials to optimize care for older cancer patients.

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Case Report

ALK Inhibition in a Patient with Inflammatory Myofibroblastic Tumor Harboring CARS1-ALK Fusion: Songji Choi, Miso Kim, Sheehyun Kim, Taekeun Park, Yoonjin Kwak, Jeong Mo Bae, Hongseok Yun, Jee Hyun Kim; Received December 10, 2024 Accepted December 14, 2024 Published online December 18, 2024; DOI: https://doi.org/10.4143/crt.2024.1184 [Epub ahead of print]

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Inflammatory myofibroblastic tumor (IMT) is a rare entity, primarily affecting young individuals, often involving the abdomen, pelvis, or lung. Approximately 50% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors a viable treatment. We report a case of a 40-year-old female with metastatic IMT harboring a CARS1-ALK fusion. Initial chemotherapy failed, but targeted therapy with alectinib through the KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study led to significant tumor regression and ongoing, durable clinical improvement of 19 months. This case highlights the importance of precision medicine and raises the reappraisal of targeted agents outside of approved indications for rare cancers with actionable genomic alterations.

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Inflammatory myofibroblastic tumors of the colon in pediatrics: clinical presentation, management, and outcomes—A case report and systematic review of literature
Ismael Elhalaby, Omar Koura, Rofyda Elhalaby, Wael Zeina, Mohamed Shareef, Essam Elhalaby
International Journal of Colorectal Disease.2025;[Epub] CrossRef

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Original Articles

Hematologic malignancy

The Role of Direct Oral Anticoagulants in Managing Myeloproliferative Neoplasms Patients: Ji Yun Lee, Ju-Hyun Lee, Woochan Park, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang; Cancer Res Treat. 2025;57(2):612-620. Published online September 20, 2024; DOI: https://doi.org/10.4143/crt.2024.738

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Purpose
Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain.
Materials and Methods
We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021.
Results
Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding.
Conclusion
Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.

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Survey of Clinical Practice in Chronic Myeloproliferative Neoplasms in Croatia: A Study by the MPN Working Group Party of the Croatian Cooperative Group for Hematologic Diseases (KROHEM)
Ivan Krecak, Marko Lucijanic, Rajko Kusec
Journal of Clinical Medicine.2025; 14(5): 1524. CrossRef

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Lung and Thoracic cancer

Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study: Songji Choi, Se Hyun Kim, Sejoon Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jin Won Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee; Cancer Res Treat. 2025;57(1):70-82. Published online August 7, 2024; DOI: https://doi.org/10.4143/crt.2024.046

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Purpose
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

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Association Between TP53 Mutations and Platinum Resistance in a Cohort of High-Grade Serous Ovarian Cancer Patients: Novel Implications for Personalized Therapeutics
Clelia Madeddu, Eleonora Lai, Manuela Neri, Elisabetta Sanna, Giulia Gramignano, Sonia Nemolato, Mario Scartozzi, Sabrina Giglio, Antonio Macciò
International Journal of Molecular Sciences.2025; 26(5): 2232. CrossRef

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Review Article

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design: Hyerim Ha, Hee Yeon Lee, Jee Hyun Kim, Do Yeun Kim, Ho Jung An, SeungJin Bae, Hye-sung Park, Jin Hyoung Kang; Cancer Res Treat. 2024;56(4):991-1013. Published online May 7, 2024; DOI: https://doi.org/10.4143/crt.2024.128

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Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

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Co-Encapsulation of Multiple Antineoplastic Agents in Liposomes by Exploring Microfluidics
Sajid Asghar, Radu Iliescu, Rares-Ionut Stiufiuc, Brindusa Dragoi
International Journal of Molecular Sciences.2025; 26(8): 3820. CrossRef

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Original Articles

Gastrointestinal cancer

Longitudinal Comparative Analysis of Circulating Tumor DNA and Matched Tumor Tissue DNA in Patients with Metastatic Colorectal Cancer Receiving Palliative First-Line Systemic Anti-Cancer Therapy: Seung-been Lee, Ji-Won Kim, Hong-Geun Kim, Sung-Hyun Hwang, Kui-Jin Kim, Ju Hyun Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Koung Jin Suh, Se Hyun Kim, Jin Won Kim, Yu Jung Kim, Jee Hyun Kim, Nak-Jung Kwon, Keun-Wook Lee; Cancer Res Treat. 2024;56(4):1171-1182. Published online April 29, 2024; DOI: https://doi.org/10.4143/crt.2024.016

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Purpose
This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy.
Materials and Methods
We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data.
Results
Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival.
Conclusion
While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer’s clonal evolution. Additionally, baseline-ctDNA’s VAF values were prognostic after treatment.

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Precision-Guided Durable Response From Venetoclax With Decitabine in a Patient With a Metastatic Refractory IDH2 -Mutant Cholangiocarcinoma
Eylül Özgü, Ünal Metin Tokat, Ashkan Adibi, Şevval Nur Bilgiç, Esranur Aydın, Onur Tutar, Mutlu Demiray
JCO Precision Oncology.2025;[Epub] CrossRef
Evolution of Neo-RAS-WT in Circulating Tumor DNA from First-Line to Subsequent Therapies in Metastatic Colorectal Cancer
Marco Siringo, Michela De Meo, Irene Bottillo, Paola Grammatico, Enrico Cortesi, Chiara Nicolazzo, Paola Gazzaniga
Cancers.2025; 17(7): 1070. CrossRef

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Breast cancer

PD-L1 (SP142) Expression in Primary and Recurrent/Metastatic Triple-Negative Breast Cancers and Its Clinicopathological Significance: Eun Kyung Han, Ji Won Woo, Koung Jin Suh, Se Hyun Kim, Jee Hyun Kim, So Yeon Park; Cancer Res Treat. 2024;56(2):557-566. Published online December 12, 2023; DOI: https://doi.org/10.4143/crt.2023.1025

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Purpose
The programmed death-ligand 1 (PD-L1) SP142 assay identifies patients with triple-negative breast cancer (TNBC) who are most likely to respond to the anti–PD-L1 agent atezolizumab. We aimed to compare PD-L1 (SP142) expression between primary and recurrent/metastatic TNBCs and elucidate the clinicopathological features associated with its expression.
Materials and Methods
Primary and recurrent/metastatic TNBCs tested with PD-L1 (SP142) were collected, and clinicopathological information of these cases was obtained through a review of slides and medical records.
Results
PD-L1 (SP142) positivity was observed in 50.9% (144/283) of primary tumors and 37.8% (31/82) of recurrent/metastatic TNBCs with a significant difference. Recurrent or metastatic sites were associated with PD-L1 positivity, with high PD-L1 positivity in the lung, breast, and soft tissues, and low positivity in the bone, skin, liver, and brain. When comparing PD-L1 expression between primary and matched recurrent/metastatic TNBCs using 55 paired samples, 20 cases (36.4%) showed discordance; 10 cases revealed positive conversion, and another 10 cases revealed negative conversion during metastatic progression. In primary TNBCs, PD-L1 expression was associated with a higher histologic grade, lower T category, pushing border, and higher tumor-infiltrating lymphocyte infiltration. In survival analyses, PD-L1 positivity, especially high positivity, was found to be associated with favorable prognosis of patients.
Conclusion
PD-L1 (SP142) expression was lower in recurrent/metastatic TNBCs, and substantial cases showed discordance in its expression between primary and recurrent/metastatic sites, suggesting that multiple sites may need to be tested for PD-L1 (SP142) when considering atezolizumab therapy. PD-L1 (SP142)–positive TNBCs seems to be associated with favorable clinical outcomes.

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Discrepancy of PD1/ PD-L1 status between primary and metastatic triple negative breast cancer in diagnostic biopsies
Manar Moustafa, Basma Hamed Ibrahim
Revista de Senología y Patología Mamaria.2025; 38(3): 100680. CrossRef
Solamargine inhibits gastric cancer progression via inactivation of STAT3/PD‑L1 signaling
Xiongxiang Liu, Lin Song, Wen Liu, Bin Liu, Lang Liu, Yao Su
Molecular Medicine Reports.2024;[Epub] CrossRef
Prevalence of Programmed Death-Ligand 1 Positivity Using SP142 in Patients With Advanced Stage Triple-Negative Breast Cancer in Malaysia: A Cross-Sectional Study
Pathmanathan Rajadurai, Ning Yi Yap, Seow Fan Chiew, Reena Rahayu Md Zin, Suria Hayati Md Pauzi, Aniqah Shamimi Binti Jaafar, Azyani Yahaya, Lai Meng Looi
Journal of Breast Cancer.2024; 27(6): 362. CrossRef

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Special Article

Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP: Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim; Cancer Res Treat. 2024;56(3):721-742. Published online November 29, 2023; DOI: https://doi.org/10.4143/crt.2023.1043

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In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

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Real-World Data: Implementation and Outcomes of Next-Generation Sequencing in the MENA Region
Rami Mahfouz, Reine Abou Zeidane, Tasnim Diab, Ali Tarhini, Eman Sbaity, Houry Kazarian, Yomna El Zibaoui, Nour Sabiha Naji, Mounir Barake, Hazem I. Assi
Diagnostics.2025; 15(10): 1183. CrossRef
Exploring PIXE Applications in Oncology: A Comprehensive Review
G. J. Naga Raju
International Journal of Advanced Research in Science, Communication and Technology.2025; : 261. CrossRef

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Original Article

General

Impact of Patient Sex on Adverse Events and Unscheduled Utilization of Medical Services in Cancer Patients Undergoing Adjuvant Chemotherapy: A Multicenter Retrospective Cohort Study: Songji Choi, Seyoung Seo, Ju Hyun Lee, Koung Jin Suh, Ji-Won Kim, Jin Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jwa Hoon Kim, Tae Won Kim, Yong Sang Hong, Sun Young Kim, Jeong Eun Kim, Sang-We Kim, Dae Ho Lee, Jae Cheol Lee, Chang-Min Choi, Shinkyo Yoon, Su-Jin Koh, Young Joo Min, Yongchel Ahn, Hwa Jung Kim, Jin Ho Baek, Sook Ryun Park, Jee Hyun Kim; Cancer Res Treat. 2024;56(2):404-413. Published online November 7, 2023; DOI: https://doi.org/10.4143/crt.2023.784

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Purpose
The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex.
Materials and Methods
This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea.
Results
A total of 1,170 patients with colorectal, gastric, or non–small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits.
Conclusion
Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

Citations

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Cancer care for transgender and gender‐diverse people: Practical, literature‐driven recommendations from the Multinational Association of Supportive Care in Cancer
Elizabeth J. Cathcart‐Rake, Alexandre Chan, Alvaro Menendez, Denise Markstrom, Carla Schnitzlein, Yee Won Chong, Don S. Dizon
CA: A Cancer Journal for Clinicians.2025; 75(1): 68. CrossRef
Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats
Chiara Di Marino, Álvaro Llorente-Berzal, Alba M. Diego, Ariadni Bella, Laura Boullon, Esther Berrocoso, Michelle Roche, David P. Finn
Frontiers in Pharmacology.2025;[Epub] CrossRef
[Translated article] Toxicity of the FOLFOX-6 regimen, with or without 5-fluorouracil bolus, in metastatic colorectal cancer
María Teresa Garrido Martínez, María Rodríguez Jorge, Ignacio García Giménez, María Isabel Guzmán Ramos, Salvador Grutzmancher Sáiz, Victoria Aviñó Tarazona
Farmacia Hospitalaria.2025;[Epub] CrossRef
The Influence of Tumor Burden Score and Lymph Node Metastasis on the Survival Benefit of Adjuvant Chemotherapy in Intrahepatic Cholangiocarcinoma
Jun Kawashima, Yutaka Endo, Selamawit Woldesenbet, Mujtaba Khalil, Miho Akabane, François Cauchy, Feng Shen, Shishir Maithel, Irinel Popescu, Minoru Kitago, Matthew J. Weiss, Guillaume Martel, Carlo Pulitano, Luca Aldrighetti, George Poultsides, Andrea Ru
Annals of Surgical Oncology.2025; 32(6): 4341. CrossRef
Toxicidad del esquema FOLFOX-6, asociado o no a bolo de 5-fluorouracilo, en cáncer colorrectal metastásico
María Teresa Garrido Martínez, María Rodríguez Jorge, Ignacio García Giménez, María Isabel Guzmán Ramos, Salvador Grutzmancher Sáiz, Victoria Aviñó Tarazona
Farmacia Hospitalaria.2024;[Epub] CrossRef

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Erratum

ERRATUM: Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group: Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim; Cancer Res Treat. 2023;55(3):1061-1061. Published online April 21, 2023; DOI: https://doi.org/10.4143/crt.2021.1115.E; Corrects: Cancer Res Treat 2022;54(1):1

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Citations

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Real-World Data: Implementation and Outcomes of Next-Generation Sequencing in the MENA Region
Rami Mahfouz, Reine Abou Zeidane, Tasnim Diab, Ali Tarhini, Eman Sbaity, Houry Kazarian, Yomna El Zibaoui, Nour Sabiha Naji, Mounir Barake, Hazem I. Assi
Diagnostics.2025; 15(10): 1183. CrossRef

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Original Articles

Breast cancer

A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03): Dae-Won Lee, Bhumsuk Keam, Keun Seok Lee, Jin-Hee Ahn, Joohyuk Sohn, Jin Seok Ahn, Moon Hee Lee, Jee Hyun Kim, Kyung Eun Lee, Hyo Jung Kim, Si-Young Kim, Yeon Hee Park, Chan-Young Ock, Kyung-Hun Lee, Sae-Won Han, Sung-Bae Kim, Young Hyuck Im, Hyun Cheol Chung, Do-Youn Oh, Seock-Ah Im; Cancer Res Treat. 2023;55(2):523-530. Published online November 8, 2022; DOI: https://doi.org/10.4143/crt.2022.1360

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Purpose
This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer.
Materials and Methods
Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events.
Results
A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%).
Conclusion
This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

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Unraveling the immune landscape and therapeutic biomarker PMEPA1 for oxaliplatin resistance in colorectal cancer: A comprehensive approach
Zhengguang Zhang, Tianming Lu, Zhe Zhang, Zixian Liu, Ruoning Qian, Ruogu Qi, Fuqiong Zhou, Min Li
Biochemical Pharmacology.2024; 222: 116117. CrossRef
Efficacy and safety of utidelone plus capecitabine in advanced first-line therapy for metastatic breast cancer: A multicenter real-world study
Pingping Bi, Xi Wang, Rui Liu, Xiuqin Li, Shanrong Wei, Jiawen Zhao, Xin Tan, Fan Zhang, Qing Mao, Ying Zhang, Baoyan Tang, Xueqiong Xun, Rong Guo, Kai Zheng, Shaoqiang Zhou, Shicong Tang
Surgery Open Science.2023; 16: 171. CrossRef

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The Pattern of Care for Brain Metastasis from Breast Cancer over the Past 10 Years in Korea: A Multicenter Retrospective Study (KROG 16-12): Jae Sik Kim, Kyubo Kim, Wonguen Jung, Kyung Hwan Shin, Seock-Ah Im, Hee-Jun Kim, Yong Bae Kim, Jee Suk Chang, Jee Hyun Kim, Doo Ho Choi, Yeon Hee Park, Dae Yong Kim, Tae Hyun Kim, Byung Ock Choi, Sea-Won Lee, Suzy Kim, Jeanny Kwon, Ki Mun Kang, Woong-Ki Chung, Kyung Su Kim, Ji Ho Nam, Won Sup Yoon, Jin Hee Kim, Jihye Cha, Yoon Kyeong Oh, In Ah Kim; Cancer Res Treat. 2022;54(4):1121-1129. Published online December 31, 2021; DOI: https://doi.org/10.4143/crt.2021.1083

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Purpose
We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea.
Materials and Methods
We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients).
Results
Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance.
Conclusion
The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

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Comparison of initial and sequential salvage brain-directed treatment in patients with 1–4 vs. 5–10 brain metastases from breast cancer (KROG 16–12)
Jae Sik Kim, Kyubo Kim, Wonguen Jung, Kyung Hwan Shin, Seock-Ah Im, Hee-Jun Kim, Yong Bae Kim, Jee Suk Chang, Jee Hyun Kim, Doo Ho Choi, Yeon Hee Park, Dae Yong Kim, Tae Hyun Kim, Byung Ock Choi, Sea-Won Lee, Suzy Kim, Jeanny Kwon, Ki Mun Kang, Woong-Ki C
Breast Cancer Research and Treatment.2023; 200(1): 37. CrossRef

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Special Article

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group: Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim; Cancer Res Treat. 2022;54(1):1-9. Published online December 13, 2021; DOI: https://doi.org/10.4143/crt.2021.1115; Correction in: Cancer Res Treat 2023;55(3):1061

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Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

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Scientific Reports.2025;[Epub] CrossRef
Expert Consensus on Molecular Tumor Boards in Taiwan: Joint Position Paper by the Taiwan Oncology Society and the Taiwan Society of Pathology
Ming-Huang Chen, Wan-Shan Li, Bin-Chi Liao, Chiao-En Wu, Chien-Feng Li, Chia-Hsun Hsieh, Feng-Che Kuan, Huey-En Tzeng, Jen-Fan Hang, Nai-Jung Chiang, Tse-Ching Chen, Tom Wei-Wu Chen, John Wen-Cheng Chang, Yao-Yu Hsieh, Yen-Lin Chen, Yi-Chen Yeh, Yi-Hsin L
Journal of Cancer Research and Practice.2024;[Epub] CrossRef
Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II
Sun Young Kim, Jee Hyun Kim, Tae-Yong Kim, Sook Ryun Park, Shinkyo Yoon, Soohyeon Lee, Se-Hoon Lee, Tae Min Kim, Sae-Won Han, Hye Ryun Kim, Hongseok Yun, Sejoon Lee, Jihun Kim, Yoon-La Choi, Kui Son Choi, Heejung Chae, Hyewon Ryu, Gyeong-Won Lee, Dae Youn
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I. Vanni, L. Pastorino, V. Andreotti, D. Comandini, G. Fornarini, M. Grassi, A. Puccini, E. T. Tanda, A. Pastorino, V. Martelli, L. Mastracci, F. Grillo, F. Cabiddu, A. Guadagno, S. Coco, E. Allavena, F. Barbero, W. Bruno, B. Dalmasso, S. E. Bellomo, C. M
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Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP
Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun
Journal of Pathology and Translational Medicine.2024; 58(4): 147. CrossRef
Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP
Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun
Cancer Research and Treatment.2024; 56(3): 721. CrossRef
Nationwide precision oncology pilot study: KOrean Precision Medicine Networking Group Study of MOlecular profiling-guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) KCSG AL-20-05
T.-Y. Kim, S.Y. Kim, J.H. Kim, H.A. Jung, Y.J. Choi, I.G. Hwang, Y. Cha, G.-W. Lee, Y.-G. Lee, T.M. Kim, S.-H. Lee, S. Lee, H. Yun, Y.L. Choi, S. Yoon, S.W. Han, T.-Y. Kim, T.W. Kim, D.Y. Zang, J.H. Kang
ESMO Open.2024; 9(10): 103709. CrossRef
Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers
Yongjun Cha, Sheehyun Kim, Sae-Won Han
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Mutational evolution after chemotherapy‐progression in metastatic colorectal cancer revealed by circulating tumor DNA analysis
Sheehyun Kim, Yongjun Cha, Yoojoo Lim, Hanseong Roh, Jun‐Kyu Kang, Kyung‐Hun Lee, Min Jung Kim, Ji Won Park, Seung‐Bum Ryoo, Hwang‐Phill Kim, Seung‐Yong Jeong, Kyu Joo Park, Sae‐Won Han, Tae‐You Kim
International Journal of Cancer.2023; 153(3): 571. CrossRef
Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists
Jiwon Koh, Ha Young Park, Jeong Mo Bae, Jun Kang, Uiju Cho, Seung Eun Lee, Haeyoun Kang, Min Eui Hong, Jae Kyung Won, Youn-La Choi, Wan-Seop Kim, Ahwon Lee
Journal of Pathology and Translational Medicine.2023; 57(5): 265. CrossRef
Implementation of Precision Oncology in the National Healthcare System: A Statement Proposal Endorsed by Italian Scientific Societies
Gianpiero Fasola, Maria C. Barducci, Valeria D. Tozzi, Luigi Cavanna, Saverio Cinieri, Francesco Perrone, Carmine Pinto, Antonio Russo, Anna Sapino, Francesco Grossi, Giuseppe Aprile
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Development of two 410-cancer-gene panel tests for solid tumors and liquid biopsy based on genome data of 5,143 Japanese cancer patients
Yuji SHIMODA, Takeshi NAGASHIMA, Kenichi URAKAMI, Fukumi KAMADA, Sou NAKATANI, Maki MIZUGUCHI, Masakuni SERIZAWA, Keiichi HATAKEYAMA, Keiichi OHSHIMA, Tohru MOCHIZUKI, Sumiko OHNAMI, Shumpei OHNAMI, Takeshi KAWAKAMI, Kentaro YAMAZAKI, Haruyasu MURAKAMI, H
Biomedical Research.2022; 43(4): 115. CrossRef
Clinical Implication of Molecular Tumor Board
Soohyeon Lee
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Somatic Mutations of TP53 Identified by Targeted Next-Generation Sequencing Are Poor Prognostic Factors for Primary Operable Breast Cancer: A Single-Center Study
Jung Ho Park, Mi Jung Kwon, Jinwon Seo, Ho Young Kim, Soo Kee Min, Lee Su Kim
Journal of Breast Cancer.2022; 25(5): 379. CrossRef

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Original Articles

Breast cancer

Effect of Estrogen Receptor Expression Level and Hormonal Therapy on Prognosis of Early Breast Cancer: Kyung-Hwak Yoon, Yeshong Park, Eunyoung Kang, Eun-Kyu Kim, Jee Hyun Kim, Se Hyun Kim, Koung Jin Suh, Sun Mi Kim, Mijung Jang, Bo La Yun, So Yeon Park, Hee-Chul Shin; Cancer Res Treat. 2022;54(4):1081-1090. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.890

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Purpose
Estrogen receptor (ER) expression in breast cancer plays an essential role in carcinogenesis and disease progression. Recently, tumors with low level (1%-10%) of ER expression have been separately defined as ER low positive (ER^low). It is suggested that ER^low tumors might be morphologically and behaviorally different from tumors with high ER expression (ERhigh).
Materials and Methods
Retrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for early breast cancer and had available medical records were included for analysis. Difference in clinicopathological characteristics, endocrine responsiveness and five-year recurrence-free survival was evaluated between different ER subgroups (ERhigh, ER^low, and ER-negative [ER–]).
Results
A total of 2,162 breast cancer patients were included in the analysis, Tis and T1 stage. Among them, 1,654 (76.5%) were ERhigh, 54 (2.5%) were ER^low, and 454 (21.0%) were ER^- patients. ER^low cases were associated with smaller size, higher histologic grade, positive human epidermal growth factor receptor 2, negative progesterone receptor, and higher Ki-67 expression. Recurrence rate was highest in ER– tumors and was inversely proportional to ER expression. Recurrence-free survival was not affected by hormonal therapy in the ER^low group (p=0.418).
Conclusion
ER^low breast cancer showed distinct clinicopathological features. ER^low tumors seemed to have higher recurrence rates compared to ERhigh tumors, and they showed no significant benefit from hormonal therapy. Future large scale prospective studies are necessary to validate the treatment options for ER^low breast cancer.

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CYP2D6 Genotyping for Optimization of Tamoxifen Therapy in Indonesian Women with ER+ Breast Cancer
Baitha Palanggatan Maggadani, Kathleen Irena Junusmin, Fatma Aldila, Jessica Audrienna, Bijak Rabbani, Yusuf Maulana, Sabrina Gabriel Tanu, Gabriella Gabriella, Margareta Amelia, Faustina Audrey Agatha, Marco Wijaya, Stevany Tiurma Sormin, Caroline Mahend
Journal of Personalized Medicine.2025; 15(3): 93. CrossRef
Prognosis, clinicopathological characteristics, and treatment patterns of patients with ER-intermediate-positive breast cancer undergoing long-term follow-up
N. Matsumoto, Y. Wanifuchi-Endo, T. Fujita, T. Asano, M. Terada, K. Nozawa, M. Mori, A. Isogai, Y. Niwa, H. Kato, M. Komura, T. Toyama
ESMO Open.2025; 10(4): 104508. CrossRef
ER-positive and BRCA2-mutated breast cancer: a literature review
Pu-Chun Li, Yi-Fan Zhu, Wen-Ming Cao, Bei Li
European Journal of Medical Research.2024;[Epub] CrossRef
Affibody PET Imaging of HER2-Expressing Cancers as a Key to Guide HER2-Targeted Therapy
Nina Eissler, Renske Altena, Ali Alhuseinalkhudhur, Olga Bragina, Joachim Feldwisch, Guido Wuerth, Annika Loftenius, Nikolai Brun, Rimma Axelsson, Vladimir Tolmachev, Jens Sörensen, Fredrik Y. Frejd
Biomedicines.2024; 12(5): 1088. 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
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
Is the percentage of hormone receptor positivity in HR+ HER2-metastatic breast cancer patients receiving CDK 4/6 inhibitor with endocrine therapy predictive and prognostic?
Merve Keskinkilic, Huseyin Salih Semiz, Tugba Yavuzsen, Ilhan Oztop
Frontiers in Oncology.2024;[Epub] CrossRef
Rat Models of Hormone Receptor-Positive Breast Cancer
Raquel Nicotra, Catrin Lutz, Hendrik A. Messal, Jos Jonkers
Journal of Mammary Gland Biology and Neoplasia.2024;[Epub] CrossRef
Immune and gene-expression profiling in estrogen receptor low and negative early breast cancer
Davide Massa, Claudio Vernieri, Lorenzo Nicolè, Carmen Criscitiello, Florence Boissière-Michot, Séverine Guiu, Angélique Bobrie, Gaia Griguolo, Federica Miglietta, Andrea Vingiani, Riccardo Lobefaro, Beatrice Taurelli Salimbeni, Claudia Pinato, Francesca
JNCI: Journal of the National Cancer Institute.2024; 116(12): 1914. CrossRef
Trends in the incidence and survival of women with hormone receptor-positive breast cancer from 1990 to 2019: a large population-based analysis
Hongbo Huang, Tingting Wei, Aijie Zhang, Heng Zhang, Lingquan Kong, Yunhai Li, Fan Li
Scientific Reports.2024;[Epub] CrossRef
The “lows”: Update on ER-low and HER2-low breast cancer
Nicola Fusco, Giuseppe Viale
The Breast.2024; 78: 103831. CrossRef
Estrogenized HSA induced high-affinity autoantibodies in breast cancer - Novel biomarker for early detection
Subuhi Sherwani, Mohd Wajid Ali Khan, Wahid Ali Khan, Saravanan Rajendrasozhan, Khalid Al-Motair, Hamda Khan, Saheem Ahmad
Frontiers in Oncology.2024;[Epub] CrossRef
Transcription factors and hormone receptors: Sex‑specific targets for cancer therapy (Review)
Juyeon Kim, Hyobin Bang, Cheyun Seong, Eun-Sook Kim, Sun Kim
Oncology Letters.2024;[Epub] CrossRef
Impact of prolactin treatment on enhancing the cellular responses of MCF7 breast cancer cells to tamoxifen treatment
Anwar Shams
Discover Oncology.2024;[Epub] CrossRef
Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL
Xujuan Zhang, Pengxiang Zhao, Mingshen Ma, Hao Wu, Rui Liu, Ziyi Liu, Zisong Cai, Mengyu Liu, Fei Xie, Xuemei Ma
Frontiers in Medicine.2023;[Epub] CrossRef
Assessment of breast cytoarchitecture and its associated axillary lymph node status under normal and pathological conditions in Egyptian women
Omnia Mansour, Amani Kazem, Abeer El Wakil
Tissue and Cell.2023; 85: 102244. CrossRef
Estrogen-Receptor-Low-Positive Breast Cancer: Pathological and Clinical Perspectives
Christina Panagiotis Malainou, Nikolina Stachika, Aikaterini Konstantina Damianou, Aristotelis Anastopoulos, Ioanna Ploumaki, Efthymios Triantafyllou, Konstantinos Drougkas, Georgia Gomatou, Elias Kotteas
Current Oncology.2023; 30(11): 9734. CrossRef

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A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer: Jung Sun Kim, Koung Jin Suh, Dae-Won Lee, Go-un Woo, Miso Kim, Se Hyun Kim, Han Suk Ryu, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, So Yeon Park, In Ae Park, Jee Hyun Kim, Seock-Ah Im; Cancer Res Treat. 2022;54(2):488-496. Published online August 13, 2021; DOI: https://doi.org/10.4143/crt.2021.394

Abstract PDF PubReader ePub

Purpose
We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.
Materials and Methods
This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled.
Results
A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m² on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m² every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.
Conclusion
This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

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Long-term outcomes of a randomized, open-label, phase II study comparing cabazitaxel versus paclitaxel as neoadjuvant treatment in patients with triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE)
P. Meyer-Wilmes, J. Huober, M. Untch, J.-U. Blohmer, W. Janni, C. Denkert, P. Klare, T. Link, K. Rhiem, C. Bayer, M. Reinisch, V. Bjelic-Radisic, D.M. Zahm, C. Hanusch, C. Solbach, G. Heinrich, A.D. Hartkopf, A. Schneeweiss, P. Fasching, N. Filmann, V. Ne
ESMO Open.2024; 9(5): 103009. CrossRef
Real-world study on the effect of nab-paclitaxel treatment on clinical outcomes and laboratory parameters in patients across metastatic tumor sites
Vikas Talreja, Sangeeta Khetwani, Ethirajan Nanadagopal, Nilesh Eknath Borkar, Kunal Khobragade
International Journal of Molecular and Immuno Oncology.2024; 9: 46. CrossRef
Safety and efficacy of generic nab-paclitaxel-based therapy in Chinese patients with malignant tumors in a real-world setting: a multicenter prospective observational study
Fei He, Yancai Sun, Wenzhou Zhang, Qiongshi Wu, Donghang Xu, Zaixian Bai, Zhiying Hao, Weiyi Feng, Kanghuai Zhang, Jiang Liu, Mei Dong, Guangxuan Liu, Guohui Li
Discover Oncology.2024;[Epub] CrossRef
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Zhichao Tian, Shuping Dong, Yang Yang, Shilei Gao, Yonghao Yang, Jinpo Yang, Peng Zhang, Xin Wang, Weitao Yao
BMC Cancer.2022;[Epub] CrossRef
Paclitaxel

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Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity
Ľuboš Nižnanský, Denisa Osinová, Roman Kuruc, Alexandra Hengerics Szabó, Andrea Szórádová, Marián Masár, Žofia Nižnanská
International Journal of Molecular Sciences.2022; 23(24): 15619. CrossRef
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Hua Yang, Mu-Zi-he Zhang, Hui-wei Sun, Yan-tao Chai, Xiaojuan Li, Qiyu Jiang, Jun Hou
Frontiers in Oncology.2021;[Epub] CrossRef

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Palliative medicine

A Prognostic Model to Facilitate Palliative Care Referral in Oncology Outpatients: Yu Jung Kim, Yusuke Hiratsuka, Sang-Yeon Suh, Beodeul Kang, Si Won Lee, Hong-Yup Ahn, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jin Won Kim, Keun-Wook Lee, Jee Hyun Kim, Jong Seok Lee; Cancer Res Treat. 2022;54(2):621-629. Published online July 12, 2021; DOI: https://doi.org/10.4143/crt.2021.483

Abstract PDF PubReader ePub

Purpose
We aimed to develop a prognostic model to assist palliative care referral at least 3 months before death in advanced cancer patients treated at an outpatient medical oncology clinic.
Materials and Methods
In this prospective cohort study, a total of 200 patients were enrolled at a tertiary cancer center in South Korea. The major eligibility criterion was an expected survival of less than a year as estimated by their oncologists. We analyzed the influences of known prognostic factors along with chemotherapy status, mid-arm circumference, and triceps skinfold thickness on survival time.
Results
The mean age of the patients was 64.5 years, 36% were female, and the median survival time was 7.6 months. In the multivariate analysis, we found 6 significant factors related to poor survival: a poor Eastern Cooperative Oncology Group (ECOG) performance status (≥2), not undergoing chemotherapy, anorexia, a low lymphocyte level (<12%), a high lactate dehydrogenase (LDH) level (≥300 IU/L), and a low mid-arm circumference (<23 cm). We developed a prognostic model (score, 0-8.0) to predict 3-month survival based on the multivariate analysis. Patients who scored ≥4.0 points had a short survival of less than 3 months (p<0.001). The discriminating ability of the prognostic model using the area under the receiver operating characteristic curve (AUC) was 0.88.
Conclusion
The prognostic model using ECOG performance status, chemotherapy status, anorexia, lymphocytes, LDH, and mid-arm circumference can predict 3-month survival in medical oncology outpatients. It can alert oncologists to refer patients to palliative care specialists before it is too late.

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Clinicians’ Prediction of Survival Is Most Useful for Palliative Care Referral
Eun Hee Jung, Yusuke Hiratsuka, Sang-Yeon Suh, Seok-Joon Yoon, Beodeul Kang, Si Won Lee, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jin Won Kim, Keun-Wook Lee, Yu Jung Kim
Palliative Medicine Reports.2024; 5(1): 365. CrossRef

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Gastrointestinal Cancer

Phase II Trial of Postoperative Adjuvant Gemcitabine and Cisplatin Chemotherapy Followed by Chemoradiotherapy with Gemcitabine in Patients with Resected Pancreatic Cancer: Kyung-Hun Lee, Eui Kyu Chie, Seock-Ah Im, Jee Hyun Kim, Jihyun Kwon, Sae-Won Han, Do-Youn Oh, Jin-Young Jang, Jae-Sung Kim, Tae-You Kim, Yung-Jue Bang, Sun Whe Kim, Sung W. Ha; Cancer Res Treat. 2021;53(4):1096-1103. Published online December 30, 2020; DOI: https://doi.org/10.4143/crt.2020.928

Abstract PDF PubReader ePub

Purpose
Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.
Materials and Methods
Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m² on days 1 and 8 and cisplatin 60 mg/m² on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m²/wk), and then gemcitabine 1,000 mg/m² on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.
Results
Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.
Conclusion
Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

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Advances in Clinical Medicine.2022; 12(10): 9540. CrossRef
Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients
Alice Usai, Gregorio Di Franco, Margherita Piccardi, Perla Cateni, Luca Emanuele Pollina, Caterina Vivaldi, Enrico Vasile, Niccola Funel, Matteo Palmeri, Luciana Dente, Alfredo Falcone, Dimitri Giunchi, Alessandro Massolo, Vittoria Raffa, Luca Morelli
Cancers.2021; 13(16): 4131. CrossRef
Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
Peng Chen, Zhiwei He, Jie Wang, Jian Xu, Xueyi Jiang, Yankun Chen, Xinyuan Liu, Jianxin Jiang
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef

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Breast Cancer

Implications of Tamoxifen Resistance in Palbociclib Efficacy for Patients with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Subgroup Analyses of KCSG-BR15-10 (YoungPEARL): Jiyun Lee, Seock-Ah Im, Gun Min Kim, Kyung Hae Jung, Seok Yun Kang, In Hae Park, Jee Hyun Kim, Hee Kyung Ahn, Yeon Hee Park; Cancer Res Treat. 2021;53(3):695-702. Published online December 17, 2020; DOI: https://doi.org/10.4143/crt.2020.1246

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Purpose
YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC.
Results
In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

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Palbociclib plus endocrine therapy in hormone receptor-positive and HER2 negative metastatic breast cancer: a multicenter real-world study in the northwest of China
Jiao Yang, Bing Zhao, Xiaoling Ling, Donghui Li, Jiuda Zhao, Yonggang Lv, Guangxi Wang, Xinlan Liu, Nanlin Li, Jin Yang
BMC Cancer.2023;[Epub] CrossRef

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Prospective Validation of The Korean Cancer Study Group Geriatric Score (KG)-7, a Novel Geriatric Screening Tool, in Older Patients with Advanced Cancer Undergoing First-line Palliative Chemotherapy: Jin Won Kim, Se Hyun Kim, Yun-Gyoo Lee, In Gyu Hwang, Jin Young Kim, Su-Jin Koh, Yoon Ho Ko, Seong Hoon Shin, In Sook Woo, Soojung Hong, Tae-Yong Kim, Ji Yeon Baek, Hyun Jung Kim, Hyo Jung Kim, Myung Ah Lee, Jung Hye Kwon, Yong Sang Hong, Hun-Mo Ryoo, Kyung Hee Lee, Jee Hyun Kim; Cancer Res Treat. 2019;51(3):1249-1256. Published online January 2, 2019; DOI: https://doi.org/10.4143/crt.2018.451

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy.
Materials and Methods
Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC).
Results
The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006).
Conclusion
KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.

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Comparison of two frailty screening tools in older patients with colorectal cancer
Han Zhao, Xinlin Lu, Senshuang Zheng, Danmei Wei, Lizhong Zhao, Yuan Wang, Geertruida H. de Bock, Wenli Lu
BMC Geriatrics.2023;[Epub] CrossRef
Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study
In Gyu Hwang, Minsuk Kwon, Jin Won Kim, Se Hyun Kim, Yun-Gyoo Lee, Jin Young Kim, Su-Jin Koh, Yoon Ho Ko, Seong Hoon Shin, Soojung Hong, Tae-Yong Kim, Sun Young Kim, Hyun Jung Kim, Hyo Jung Kim, Myung Ah Lee, Jung Hye Kwon, Yong Sang Hong, Kyung Hee Lee,
Cancers.2021; 13(2): 331. CrossRef
A single-arm feasibility study of gradual dose de-escalation of antiemetic dexamethasone for older patients receiving chemotherapy
Koung Jin Suh, Seonghae Yoon, Jin Won Kim, Seo Hyun Yoon, Ji-Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jong Seok Lee, Jee Hyun Kim
Journal of Geriatric Oncology.2021; 12(6): 922. CrossRef
Predictive Value of Geriatric Oncology Screening and Geriatric Assessment in Older Patients with Solid Cancers: Protocol for a Danish prospective cohort study (PROGNOSIS-G8)
Helena Møgelbjerg Ditzel, Ann-Kristine Weber Giger, Cecilia Margareta Lund, Henrik Jørn Ditzel, Afsaneh Mohammadnejad, Per Pfeiffer, Jesper Ryg, Trine Lembrecht Jørgensen, Marianne Ewertz
Journal of Geriatric Oncology.2021; 12(8): 1270. CrossRef
The Globalization of Geriatric Oncology: From Data to Practice
Ravindran Kanesvaran, Supriya Mohile, Enrique Soto-Perez-de-Celis, Harpreet Singh
American Society of Clinical Oncology Educational Book.2020; (40): e107. CrossRef

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Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer: Junghoon Shin, Jin-Haeng Chung, Se Hyun Kim, Kyu Sang Lee, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jeong-Ok Lee, Jin-Won Kim, Yu-Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong-Seok Lee; Cancer Res Treat. 2019;51(3):1086-1097. Published online November 5, 2018; DOI: https://doi.org/10.4143/crt.2018.537

Abstract PDF PubReader ePub

Purpose
Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications.
Materials and Methods
We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival.
Results
The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival.
Conclusion
Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.

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Remarkable Response to Immune Checkpoint Inhibitor Monotherapy in an EGFR-Mutant Pulmonary Adenocarcinoma Patient With 0% Expression of PD-L1
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Redirecting Chemotherapeutics to the Endoplasmic Reticulum Increases Tumor Immunogenicity and Potentiates Anti‐PD‐L1 Therapy
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Dual inhibition of TGFβ signaling and CSF1/CSF1R reprograms tumor-infiltrating macrophages and improves response to chemotherapy via suppressing PD-L1
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SP142 PD-L1 Assays in Multiple Samples from the Same Patients with Early or Advanced Triple-Negative Breast Cancer
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Taotao Zhou, Robert Mahn, Christian Möhring, Farsaneh Sadeghlar, Carsten Meyer, Marieta Toma, Barbara Kreppel, Markus Essler, Tim Glowka, Hanno Matthaei, Jörg C. Kalff, Christian P. Strassburg, Maria A. Gonzalez-Carmona
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Chang Hyun Nam, Jaemoon Koh, Chan-Young Ock, Miso Kim, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Doo Hyun Chung, Dae Seog Heo
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Lei Tu, Renguo Guan, Hanting Yang, Yu Zhou, Weifeng Hong, Liheng Ma, Guangzhe Zhao, Min Yu
International Journal of Cancer.2020; 147(2): 423. CrossRef
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Jiahang Mo, Xiao Hu, Lihu Gu, Bangsheng Chen, Parikshit Asutosh Khadaroo, Zefeng Shen, Lei Dong, Yuqi Lv, Marylin Nyaradzo Chitumba, Jiequan Liu
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Kathrin Gennen, Lukas Käsmann, Julian Taugner, Chukwuka Eze, Monika Karin, Olarn Roengvoraphoj, Jens Neumann, Amanda Tufman, Michael Orth, Simone Reu, Claus Belka, Farkhad Manapov
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Jaanika Narits, Hannes Tamm, Jana Jaal
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Yun Liang, Minghua Yu, Caiyun Zhou, Xiaojun Zhu
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Rui Jin, Jing Zhao, Lexin Xia, Qin Li, Wen Li, Ling Peng, Yang Xia
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Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors
Lorenzo Galluzzi, Juliette Humeau, Aitziber Buqué, Laurence Zitvogel, Guido Kroemer
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Malene Støchkel Frank, Uffe Bødtger, Asbjørn Høegholm, Inger Merete Stamp, Julie Gehl
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The Mechanisms of PD-L1 Regulation in Non-Small-Cell Lung Cancer (NSCLC): Which Are the Involved Players?
Giuseppe Lamberti, Monia Sisi, Elisa Andrini, Arianna Palladini, Francesca Giunchi, Pier-Luigi Lollini, Andrea Ardizzoni, Francesco Gelsomino
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Avital Vorontsova, Tal Kan, Ziv Raviv, Yuval Shaked
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Adjuvant Chemotherapy Increases Programmed Death-Ligand 1 (PD-L1) Expression in Non–small Cell Lung Cancer Recurrence
Max Lacour, Stefanie Hiltbrunner, Seok-Yun Lee, Alex Soltermann, Elisabeth Jane Rushing, Davide Soldini, Walter Weder, Alessandra Curioni-Fontecedro
Clinical Lung Cancer.2019; 20(5): 391. CrossRef
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Hyojin Kim, Jin-Haeng Chung
Journal of Pathology and Translational Medicine.2019; 53(4): 199. CrossRef

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485 Download
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Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma: Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo; Cancer Res Treat. 2019;51(2):510-518. Published online June 13, 2018; DOI: https://doi.org/10.4143/crt.2018.226

Abstract PDF Supplementary Material PubReader ePub

Purpose
The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC).
Materials and Methods
This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints.
Results
A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8).
Conclusion
OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.

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Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01): In Hae Park, Seock-Ah Im, Kyung Hae Jung, Joo Hyuk Sohn, Yeon Hee Park, Keun Seok Lee, Sung Hoon Sim, Kyong-Hwa Park, Jee Hyun Kim, Byung Ho Nam, Hee-Jun Kim, Tae-Yong Kim, Kyung-Hun Lee, Sung-Bae Kim, Jin-Hee Ahn, Suee Lee, Jungsil Ro; Cancer Res Treat. 2019;51(1):43-52. Published online February 14, 2018; DOI: https://doi.org/10.4143/crt.2017.562

Abstract PDF PubReader ePub

Purpose
We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC).
Materials and Methods
A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.
Results
There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea.
Conclusion
Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

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Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer: Soomin Ahn, Hyun Jeong Kim, Milim Kim, Yul Ri Chung, Eunyoung Kang, Eun-Kyu Kim, Se Hyun Kim, Yu Jung Kim, Jee Hyun Kim, In Ah Kim, So Yeon Park; Cancer Res Treat. 2018;50(4):1418-1432. Published online January 24, 2018; DOI: https://doi.org/10.4143/crt.2017.552

Abstract PDF PubReader ePub

Purpose
Alteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST.
Materials and Methods
The pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed.
Results
Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup.
Conclusion
ER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.

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Changing the phenotype of breast cancer in the process treatment: literature review
M. S. Shvedsky, R. I. Tamrazov, T. P. Shevlyukova, L. A. Bakhova
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HER2-low breast cancer and response to neoadjuvant chemotherapy: a population-based cohort study
Ximena Baez-Navarro, Mieke R. van Bockstal, Agnes Jager, Carolien H.M. van Deurzen
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NGS mutational status on first diagnostic tissue, liquid biopsy and mastectomy in G2–G3 breast cancer
Carmen Maria Ardeleanu, Maria Victoria Olinca , Cristian Gabriel Viişoreanu , Horaţiu Alin Mureşan , Adriana Tecuceanu-Vulpe , Georgiana Manole , Iulia Elena Gune , Bianca Gălăţeanu , Andreea-Corina Ilie-Petrov
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Applicability of Quantum Dots in Breast Cancer Diagnostic and Therapeutic Modalities—A State-of-the-Art Review
Dominika Kunachowicz, Karolina Kłosowska, Natalia Sobczak, Marta Kepinska
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Progesterone and progesterone receptors in breast cancer: past, present, and future
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Luo Wang, Qi Jiang, Meng-Ye He, Peng Shen
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A Novel Prognostic Nomogram for Predicting Risks of Distant Failure in Patients with Invasive Breast Cancer Following Postoperative Adjuvant Radiotherapy: Yu Jin Lim, Sea-Won Lee, Noorie Choi, Jeanny Kwon, Keun-Yong Eom, Eunyoung Kang, Eun-Kyu Kim, Jee Hyun Kim, Yu Jung Kim, Se Hyun Kim, So Yeon Park, In Ah Kim; Cancer Res Treat. 2018;50(4):1140-1148. Published online December 7, 2017; DOI: https://doi.org/10.4143/crt.2017.508

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to identify predictors for distant metastatic behavior and build a related prognostic nomogram in breast cancer.
Materials and Methods
A total of 1,181 patients with non-metastatic breast cancer between 2003 and 2011 were analyzed. To predict the probability of distant metastasis, a nomogram was constructed based on prognostic factors identified using a Cox proportional hazards model.
Results
The 7-year overall survival and 5-year post-progression survival of locoregional versus distant recurrence groups were 67.6% versus 39.1% (p=0.027) and 54.2% versus 33.5% (p=0.043), respectively. Patients who developed distant metastasis showed early and late mortality risk peaks within 3 and after 5 years of follow-up, respectively, but a broad and low risk increment was observed in other patients with locoregional relapse. In multivariate analysis of distant metastasis-free interval, age (≥ 45 years vs. < 45 years), molecular subtypes (luminal A vs. luminal B, human epidermal growth receptor 2, and triple negative), T category (T1 vs. T2-3 and T4), and N category (N0 vs. N1 and N2-3) were independently associated (p < 0.05 for all). Regarding the significant factors, a well-validated nomogram was established (concordance index, 0.812). The risk score level of patients with initial brain failure was higher than those of non-brain sites (p=0.029).
Conclusion
The nomogram could be useful for predicting the individual probability of distant recurrence in breast cancer. In high-risk patients based on the risk scores, more aggressive systemic therapy and closer surveillance for metastatic failure should be considered.

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Predicting Patterns of Distant Metastasis in Breast Cancer Patients following Local Regional Therapy Using Machine Learning
Audrey Shiner, Alex Kiss, Khadijeh Saednia, Katarzyna J. Jerzak, Sonal Gandhi, Fang-I Lu, Urban Emmenegger, Lauren Fleshner, Andrew Lagree, Marie Angeli Alera, Mateusz Bielecki, Ethan Law, Brianna Law, Dylan Kam, Jonathan Klein, Christopher J. Pinard, Ale
Genes.2023; 14(9): 1768. CrossRef
Nomograms for Predicting Specific Distant Metastatic Sites and Overall Survival of Breast Invasive Ductal Carcinoma Patients After Surgery: A Large Population-Based Study
Yuqian Feng, Yiting Zhang, Yuying Xiang, Kaibo Guo, Huimin Jin, Shanming Ruan, Zhuoya Guan
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Cost-effectiveness of postmastectomy hypofractionated radiation therapy vs conventional fractionated radiation therapy for high-risk breast cancer
Jing Yang, Shu-Nan Qi, Hui Fang, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Wei-Hu Wang, Yong Yang, Yu Tang, Hua Ren, Bo Chen, Ning-Ning Lu, Yuan Tang, Ning Li, Hao Jing, Shu-Lian Wang, Ye-Xiong Li
The Breast.2021; 58: 72. CrossRef
Prediction of distant metastatic recurrence by tumor-infiltrating lymphocytes in hormone receptor-positive breast cancer
Koji Takada, Shinichiro Kashiwagi, Yuka Asano, Wataru Goto, Rika Kouhashi, Akimichi Yabumoto, Sae Ishihara, Tamami Morisaki, Masatsune Shibutani, Hiroaki Tanaka, Kosei Hirakawa, Masaichi Ohira
BMC Women's Health.2021;[Epub] CrossRef
Nomogram for the personalisation of radiotherapy treatments in breast cancer patients
Inmaculada Beato Tortajada, Carlos Ferrer Albiach, Virginia Morillo Macias
The Breast.2021; 60: 255. CrossRef
Prognostic Factors and Nomograms to Predict Overall and Cancer-Specific Survival for Children with Wilms’ Tumor
Fucai Tang, Hanbin Zhang, Zechao Lu, Jiamin Wang, Chengwu He, Zhaohui He
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Score for the Survival Probability in Metastasis Breast Cancer: A Nomogram-Based Risk Assessment Model
Zhenchong Xiong, Guangzheng Deng, Xinjian Huang, Xing Li, Xinhua Xie, Jin Wang, Zeyu Shuang, Xi Wang
Cancer Research and Treatment.2018; 50(4): 1260. CrossRef

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Phase 1 Studies of Poziotinib, an Irreversible Pan-HER Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors: Tae Min Kim, Keun-Wook Lee, Do-Youn Oh, Jong-Seok Lee, Seock-Ah Im, Dong-Wan Kim, Sae-Won Han, Yu Jung Kim, Tae-You Kim, Jee Hyun Kim, Hyesun Han, Woo Ho Kim, Yung-Jue Bang; Cancer Res Treat. 2018;50(3):835-842. Published online August 29, 2017; DOI: https://doi.org/10.4143/crt.2017.303

Abstract PDF Supplementary Material PubReader ePub

Purpose
Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors.
Materials and Methods
Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort.
Results
A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Doselimiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer).
Conclusion
Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.

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Experiences and Opinions Related to End-of-Life Discussion: From Oncologists' and Resident Physicians' Perspectives: Su-Jin Koh, Shinmi Kim, JinShil Kim, Bhumsuk Keam, Dae Seog Heo, Kyung Hee Lee, Bong-Seog Kim, Jee Hyun Kim, Hye Jung Chang, Sun Kyung Baek; Cancer Res Treat. 2018;50(2):614-623. Published online July 3, 2017; DOI: https://doi.org/10.4143/crt.2016.446

Abstract PDF PubReader ePub

Purpose
The aims of this study were to explore how oncologists and resident physicians practice end-of-life (EOL) discussions and to solicit their opinions on EOL discussions as a means to improve the quality of EOL care.
Materials and Methods
A survey questionnaire was developed to explore the experiences and opinions about EOL discussions among oncologists and residents. Descriptive statistics, the t test, and the chisquare test were performed for the analyses.
Results
A total of 147 oncologists and 229 residents participated in this study. The study respondents reported diverse definitions of “terminal state,” and mostrespondents tried to disclose the patient’s condition to the patient and/or family members. Both groups were involved in EOL care discussions, with a rather low satisfaction level (57.82/100). The best timing to initiate discussionwas consideredwhen metastasis or disease recurrence occurred orwhen withdrawal of chemotherapy was anticipated. Furthermore, the study respondents suggested that patients and their family members should be included in the EOL discussion. Medical, legal, and ethical knowledge and communication difficulties along with practical issues were revealed as barriers and facilitators for EOL discussion.
Conclusion
This study explored various perspectives of oncologists and resident physicians for EOL discussion. Since the Life-Sustaining-Treatment Decision-Making Act will be implemented shortly in Korea, now is the time for oncologists and residents to prepare themselves by acquiring legal knowledge and communication skills. To achieve this, education, training, and clinical tools for healthcare professionals are required.

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Issues and implications of the life-sustaining treatment decision act: comparing the data from the survey and clinical data of inpatients at the end-of-life process
Eunjeong Song, Dongsoon Shin, Jooseon Lee, Seonyoung Yun, Minjeong Eom, Suhee Oh, Heejung Lee, Jiwan Lee, Rhayun Song
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Experience and perspectives of end-of-life care discussion and physician orders for life-sustaining treatment of Korea (POLST-K): a cross-sectional study
Hyeon-Su Im, Insook Lee, Shinmi Kim, Jong Soo Lee, Ju-Hee Kim, Jae Young Moon, Byung Kyu Park, Kyung Hee Lee, Myung Ah Lee, Sanghoon Han, Yoonki Hong, Hyeyeoung Kim, Jaekyung Cheon, Su-Jin Koh
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Sita de Vries, Mary-Joanne Verhoef, Sigrid Cornelia Johanna Maria Vervoort, Yvette Milene van der Linden, Saskia Cornelia Constantia Maria Teunissen, Everlien de Graaf
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Epidemiology of Intracranial Metastases in Korea: A National Cohort Investigation: Tackeun Kim, Changhoon Song, Jung Ho Han, In-Ah Kim, Yu Jung Kim, Se Hyun Kim, Jee Hyun Kim, Chae-Yong Kim; Cancer Res Treat. 2018;50(1):164-174. Published online March 21, 2017; DOI: https://doi.org/10.4143/crt.2017.072

Abstract PDF PubReader ePub

Purpose
To investigate the epidemiologic features of intracranial metastases (ICMET) in Korea, we performed a cohort study using the National Health Insurance Service–National Sample Cohort database, which comprised healthcare usage information of approximately 1 million Korean individuals over 12 years.
Materials and Methods
We enrolled 998,602 subjects, after excluding 18,218 subjects diagnosed with any cancer during the washout period (2002-2004). The observation period was 9 years (2005-2013; 8,725,438 person-years). The initial diagnosis date of ICMET and the primary cancer was recorded. The incidence was determined based on the number of incident cases and observation size, whereas survival was estimated using death statistics from the database.
Results
Through observation period, a total 776 subjects developed ICMET. The age-standardized incidence of ICMET was 8.2 per 100,000 person-years. The mean interval between the initial diagnosis date of the primary cancer and ICMET was 13.1 months. Patients with ICMET had shorter survival than those without ICMET (30.9 months vs. 81.4 months, p < 0.001). The ICMET incidence among the cancer patients was 5.0 per 1,000 personyears; it was highest in lung cancer cases, followed by breast and liver cancer cases. Moreover, ICMET from lung cancer was the most common metastasis type, followed by ICMET from liver and breast cancer.
Conclusion
The incidence of ICMET was 8.2 per 100,000 person-years among the Korean population and 5.0 per 1,000 person-years among cancer patients. Most of the ICMET cases arose from lung cancer. ICMET also critically influenced survival in cancer patients.

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Joshua R. D. Pearson, Carles Puig-Saenz, Jubini E. Thomas, Lydia D. Hardowar, Murrium Ahmad, Louise C. Wainwright, Adam M. McVicar, Victoria A. Brentville, Chris J. Tinsley, A. Graham Pockley, Lindy G. Durrant, Stephanie E. B. McArdle
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Sung Jun Ahn, Bio Joo, Mina Park, Hun Ho Park, Sang Hyun Suh, Sung Gwe Ahn, Jihwan Yoo
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Jun Hyeok Jung, Kawngwoo Park, Eun Young Kim, Chan-Jong Yoo, Gi-Taek Yee, Woo-Kyung Kim, Dong-Won Shin
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Youngkyong Kim, Sung Hwan Kim, Jong Hoon Lee, Dae Gyu Kang
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Bilateral Salpingo-oophorectomy Compared to Gonadotropin-Releasing Hormone Agonists in Premenopausal Hormone Receptor–Positive Metastatic Breast Cancer Patients Treated with Aromatase Inhibitors: Koung Jin Suh, Se Hyun Kim, Kyung-Hun Lee, Tae-Yong Kim, Yu Jung Kim, Sae-Won Han, Eunyoung Kang, Eun-Kyu Kim, Kidong Kim, Jae Hong No, Wonshik Han, Dong-Young Noh, Maria Lee, Hee Seung Kim, Seock-Ah Im, Jee Hyun Kim; Cancer Res Treat. 2017;49(4):1153-1163. Published online February 27, 2017; DOI: https://doi.org/10.4143/crt.2016.463

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO).
Materials and Methods
We retrospectively analyzed data of 66 premenopausal patients with hormone receptor– positive, human epidermal growth factor receptor 2–negative recurrent and metastatic breast cancer who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015.
Results
The median patient age was 44 years. Overall, 24 (36%) received BSO and 42 (64%) received GnRHa. The clinical benefit rate was higher in the BSO group than in the GnRHa group (88% vs. 69%, p=0.092). Median progression-free survival (PFS) was longer in the BSO group, although statistical significance was not reached (17.2 months vs. 13.3 months, p=0.245). When propensity score matching was performed, the median PFS was 17.2 months for the BSO group and 8.2 months for the GnRHa group (p=0.137). Multivariate analyses revealed that the luminal B subtype (hazard ratio, 1.67; 95% confidence interval [CI], 1.08 to 2.60; p=0.022) and later-line treatment (≥ third line vs. first line; hazard ratio, 3.24; 95% CI, 1.59 to 6.59; p=0.001) were independent predictive factors for a shorter PFS. Incomplete ovarian suppression was observed in a subset of GnRHa-treated patients whose disease showed progression, with E2 levels higher than 21 pg/mL.
Conclusion
Both BSO and GnRHa were found to be effective in our AI-treated premenopausal metastatic breast cancer patient cohort. However, further studies in larger populations are needed to determine if BSO is superior to GnRHa.

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Incomplete ovarian function suppression in premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonists
Jinna Lin, Shuqi Zheng, Qiang Liu
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Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study
Yifei Chen, Ruyan Zhang, Ying Yan, Huiping Li, Guohong Song
Breast Cancer Research and Treatment.2024; 206(3): 543. CrossRef
Oophorectomy in Premenopausal Patients with Estrogen Receptor-Positive Breast Cancer: New Insights into Long-Term Effects
Fatima Khan, Kristin Rojas, Matthew Schlumbrecht, Patricia Jeudin
Current Oncology.2023; 30(2): 1794. CrossRef
Comparison of outcomes in patients with luminal type breast cancer treated with a gonadotropin-releasing hormone analog or bilateral salpingo-oophorectomy: A cohort retrospective study
Dwi Ris Andriyanto, Prihantono, Salman Ardi Syamsu, Muhammad Ihwan Kusuma, Joko Hendarto, Indra, Nilam Smaradania, Elridho Sampepajung, Asrul Mappiwali, Muhammad Faruk
Annals of Medicine & Surgery.2022;[Epub] CrossRef
Awareness of the Causes Leading to Surgical Ablation of Ovarian Function in Premenopausal Breast Cancer—A Single-Center Analysis
Joana Correia Oliveira, Filipa Costa Sousa, Inês Gante, Margarida Figueiredo Dias
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Brändli SP, Palm J, Kowalewski MP, Reichler IM
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Gebra Cuyún Carter, Maitreyee Mohanty, Keri Stenger, Claudia Morato Guimaraes, Shivaprasad Singuru, Pradeep Basa, Sheena Singh, Vanita Tongbram, Sherko Kuemmel, Valentina Guarneri, Sara M Tolaney
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Oophorectomy as a Hormonal Ablation Therapy in Metastatic and Recurrent Breast Cancer: Current Indications and Results
Islam H. Metwally, Omar Hamdy, Saleh S. Elbalka, Mohamed Elbadrawy, Dina M. Elsaid
Indian Journal of Surgical Oncology.2019; 10(3): 542. CrossRef
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Clinical Cancer Research.2018; 24(21): 5206. CrossRef

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CA19-9 or CEA Decline after the First Cycle of Treatment Predicts Survival in Advanced Biliary Tract Cancer Patients Treated with S-1 and Cisplatin Chemotherapy: Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang; Cancer Res Treat. 2017;49(3):807-815. Published online January 18, 2017; DOI: https://doi.org/10.4143/crt.2016.326

Abstract PDF PubReader ePub

Purpose
While tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) can aid in the diagnosis of biliary tract cancer, their prognostic role has not been clearly elucidated. Therefore, this study was conducted to evaluate the prognostic role of tumor markers and tumor marker change in patients with advanced biliary tract cancer.
Materials and Methods
Patients with pathologically proven metastatic or relapsed biliary tract cancer who were treated in a phase II trial of first-line S-1 and cisplatin chemotherapy were enrolled. Serum tumor markers were measured at baseline and after the first cycle of chemotherapy.
Results
Among a total of 104 patients, 80 (77%) had elevated baseline tumor markers (69 with CA 19-9 elevation and 40 with CEA). A decline ≥ 30% of the elevated tumor marker level after the first cycle of chemotherapy conferred an improved time to progression (TTP), overall survival (OS), and better chemotherapy response. Multivariate analysis revealed tumor marker decline as an independent positive prognostic factor of TTP (adjusted hazard ratio [HR], 0.44; p=0.003) and OS (adjusted HR, 0.37; p < 0.001). Subgroup analysis revealed similar results in each group of patients with CA 19-9 elevation and CEA elevation. In addition, elevated baseline CEA was associated with poor survival in both univariate and multivariate analysis.
Conclusion
Tumor marker decline was associated with improved survival in biliary tract cancer. Measuring tumor marker after the first cycle of chemotherapy can be used as an early assessment of treatment outcome.

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Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis: Seongyeong Kim, Ahrum Min, Kyung-Hun Lee, Yaewon Yang, Tae-Yong Kim, Jee Min Lim, So Jung Park, Hyun-Jin Nam, Jung Eun Kim, Sang-Hyun Song, Sae-Won Han, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, David Hangauer, Johnson Yiu-Nam Lau, Kyongok Im, Dong Soon Lee, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2017;49(3):643-655. Published online October 6, 2016; DOI: https://doi.org/10.4143/crt.2016.168

Abstract PDF Supplementary Material PubReader ePub

Purpose
KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo.
Materials and Methods
The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects.
Results
KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho- Src and proliferative-signaling molecules were down-regulated in KX-01–sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01– induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01–sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model.
Conclusion
KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.

Citations

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