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BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy
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Sung-Bae Kim, In-Gu Do, Janice Tsang, Tae-You Kim, Yoon-Sim Yap, Gerardo Cornelio, Gyungyub Gong, Soonmyung Paik, Suee Lee, Ting-Ying Ng, Sarah Park, Ho-Suk Oh, Joanne Chiu, Joohyuk Sohn, Moonhee Lee, Young-Jin Choi, Eun Mi Lee, Kyong-Hwa Park, Christos Nathaniel, Jungsil Ro
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Cancer Res Treat. 2019;51(4):1527-1539. Published online June 4, 2019
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DOI: https://doi.org/10.4143/crt.2018.598
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 Abstract
 PDF PubReader ePub
- Purpose
BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. Materials and Methods
Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored.
Results
p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib.
Conclusion
The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.
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Citations
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Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
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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)
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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
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Cancer Res Treat. 2019;51(1):43-52. Published online February 14, 2018
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DOI: https://doi.org/10.4143/crt.2017.562
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Abstract
PDFPubReaderePub
- 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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An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer
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In Hae Park, Joo Hyuk Sohn, Sung Bae Kim, Keun Seok Lee, Joo Seop Chung, Soo Hyeon Lee, Tae You Kim, Kyung Hae Jung, Eun Kyung Cho, Yang Soo Kim, Hong Suk Song, Jae Hong Seo, Hun Mo Ryoo, Sun Ah Lee, So Young Yoon, Chul Soo Kim, Yong Tai Kim, Si Young Kim, Mi Ryung Jin, Jungsil Ro
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Cancer Res Treat. 2017;49(3):569-577. Published online September 12, 2016
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DOI: https://doi.org/10.4143/crt.2016.289
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Abstract
PDFPubReaderePub
- Purpose
Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol).
Materials and Methods
Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously every 3 weeks. The primary outcome was the objective response rate (ORR).
Results
The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m2 (95.0%), and that of Genexol was 168.3±10.6 mg/m2 (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (pnon-inferiority=0.021, psuperiority=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments.
Conclusion
Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.
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A. I. Fraguas-Sánchez, C. Martín-Sabroso, A. Fernández-Carballido, A. I. Torres-Suárez
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Hao Chen, Yueyue Chen, Han Wu, Jiang-Fei Xu, Zhiwei Sun, Xi Zhang
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Arjun Prasad Tiwari, Tae In Hwang, Jung-Mi Oh, Bikendra Maharjan, Sungkun Chun, Beom Su Kim, Mahesh Kumar Joshi, Chan Hee Park, Cheol Sang Kim
ACS Applied Materials & Interfaces.2018; 10(24): 20256. CrossRef - The Blood Clearance Kinetics and Pathway of Polymeric Micelles in Cancer Drug Delivery
Xuanrong Sun, Guowei Wang, Hao Zhang, Shiqi Hu, Xin Liu, Jianbin Tang, Youqing Shen
ACS Nano.2018; 12(6): 6179. CrossRef - Different Nanoformulations Alter the Tissue Distribution of Paclitaxel, Which Aligns with Reported Distinct Efficacy and Safety Profiles
Feng Li, Huixia Zhang, Miao He, Jinhui Liao, Nianhang Chen, Yan Li, Simon Zhou, Maria Palmisano, Alex Yu, Manjunath P. Pai, Hebao Yuan, Duxin Sun
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Locoregional Recurrence by Tumor Biology in Breast Cancer Patients after Preoperative Chemotherapy and Breast Conservation Treatment
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Eunjin Jwa, Kyung Hwan Shin, Ja Young Kim, Young Hee Park, So-Youn Jung, Eun Sook Lee, In Hae Park, Keun Seok Lee, Jungsil Ro, Yeon-Joo Kim, Tae Hyun Kim
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Cancer Res Treat. 2016;48(4):1363-1372. Published online February 18, 2016
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DOI: https://doi.org/10.4143/crt.2015.456
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Abstract
PDFPubReaderePub
- Purpose
The purpose of this study is to determine whether breast cancer subtype can affect locoregional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) after neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT). Materials and Methods We evaluated 335 consecutive patients with clinical stage II-III breast cancer who received NAC plus BCT from 2002 to 2009. Patients were classified according to six molecular subtypes: luminal A (hormone receptor [HR]+/HER2–/Ki-67 < 15%, n=113), luminal B1 (HR+/HER2–/Ki-67 ≥ 15%, n=33), luminal B2 (HR+/HER2+, n=83), HER2 with trastuzumab (HER2[T+]) (HR–/HER2+/use of trastuzumab, n=14), HER2 without trastuzumab (HER2[T–]) (HR–/HER2+, n=31), and triple negative (TN) (HR–/HER2–, n=61).
Results
After a median follow-up period of 7.2 years, 26 IBTRs and 37 LRRs occurred. The 5-year LRR-free survival rates were luminal A, 96.4%; B1, 93.9%; B2, 90.3%; HER2(T+), 92.9%; HER2(T–), 78.3%; and TN, 79.6%. The 5-year IBTR-free survival rates were luminal A, 97.2%; B1, 93.9%; B2, 92.8%; HER2(T+), 92.9%; HER2(T–), 89.1%; and TN, 84.6%. In multivariate analysis, HER2(T–) (IBTR: hazard ratio, 4.2; p=0.04 and LRR: hazard ratio, 7.6; p < 0.01) and TN subtypes (IBTR: hazard ratio, 6.9; p=0.01 and LRR: hazard ratio, 8.1; p < 0.01) were associated with higher IBTR and LRR rates. A pathologic complete response (pCR) was found to show correlation with better LRR and a tendency toward improved IBTR controls in TN patients (IBTR, p=0.07; LRR, p=0.03). Conclusion The TN and HER2(T–) subtypes predict higher rates of IBTR and LRR after NAC and BCT. A pCR is predictive of improved IBTR or LRR in TN subtype.
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Effect of Time Interval between Breast-Conserving Surgery and Radiation Therapy on Outcomes of Node-Positive Breast Cancer Patients Treated with Adjuvant Doxorubicin/Cyclophosphamide Followed by Taxane
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Hyeon Kang Koh, Kyung Hwan Shin, Kyubo Kim, Eun Sook Lee, In Hae Park, Keun Seok Lee, Jungsil Ro, So-Youn Jung, Seeyoun Lee, Seok Won Kim, Han-Sung Kang, Eui Kyu Chie, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee, Seock-Ah Im, Sung Whan Ha
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Cancer Res Treat. 2016;48(2):483-490. Published online June 5, 2015
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DOI: https://doi.org/10.4143/crt.2015.111
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Abstract
PDFPubReaderePub
- Purpose
This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. Materials and Methods From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome.
Results
The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. Conclusion RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.
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Citations
Citations to this article as recorded by - MiR-210 regulates lung adenocarcinoma by targeting HIF-1α
Guolei Cao, Peiwen Fan, Ronghui Ma, Qinghe Wang, Lili He, Haiwen Niu, Qin Luo
Heliyon.2023; 9(5): e16079. CrossRef - Timing of postmastectomy radiotherapy following adjuvant chemotherapy for high-risk breast cancer: A post hoc analysis of a randomised controlled clinical trial
Si-Ye Chen, Guang-Yi Sun, Yu Tang, Hao Jing, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Xu-Ran Zhao, Yu-Chun Song, Bo Chen, Shu-Nan Qi, Yuan Tang, Ning-Ning Lu, Ning Li, Hui Fang, Ye-Xiong Li, Shu-Lian Wang
European Journal of Cancer.2022; 174: 153. CrossRef - Timing of Postmastectomy Radiotherapy Following Adjuvant Chemotherapy for High-Risk Breast Cancer: A Post-Hoc Analysis of a Randomised Controlled Clinical Trial
Si-Ye Chen, Guang-Yi Sun, Yu Tang, Hao Jing, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Xu-Ran Zhao, Yu-Chun Song, Bo Chen, Shu-Nan Qi, Yuan Tang, Ning-Ning Lu, Ning Li, Hui Fang, Ye-Xiong Li, Shu-Lian Wang
SSRN Electronic Journal .2022;[Epub] CrossRef - Social Determinants of Racial Disparities in Breast Cancer Mortality Among Black and White Women
Oluwole Adeyemi Babatunde, Jan M. Eberth, Tisha Felder, Robert Moran, Samantha Truman, James R. Hebert, Jiajia Zhang, Swann Arp Adams
Journal of Racial and Ethnic Health Disparities.2021; 8(1): 147. CrossRef - How Does the Interval Between Completion of Adjuvant Chemotherapy and Initiation of Radiotherapy Impact Clinical Outcomes in Operable Breast Cancer Patients?
Lu Cao, Cheng Xu, Gang Cai, Wei-Xiang Qi, Rong Cai, Shu-Bei Wang, Dan Ou, Min Li, Kun-Wei Shen, Jia-Yi Chen
Annals of Surgical Oncology.2021; 28(4): 2155. CrossRef - Saving the Breast Saves the Lives of Breast Cancer Patients
Mohammad Esmaeil Akbari, Maryam Khayamzadeh, Hamid Reza Mirzaei, Afshin Moradi, Atieh Akbari, Farid Moradian, Neda Khalili
International Journal of Surgical Oncology.2020; 2020: 1. CrossRef - Timing of Chemotherapy and Radiotherapy Following Breast-Conserving Surgery for Early-Stage Breast Cancer: A Retrospective Analysis
Si-Ye Chen, Yu Tang, Shu-Lian Wang, Yong-Wen Song, Hui Fang, Jian-Yang Wang, Hao Jing, Jiang-Hu Zhang, Guang-Yi Sun, Xu-Ran Zhao, Jing Jin, Yue-Ping Liu, Bo Chen, Shu-Nan Qi, Ning Li, Yuan Tang, Ning-Ning Lu, Hua Ren, Zi-Hao Yu, Ye-Xiong Li
Frontiers in Oncology.2020;[Epub] CrossRef - Evaluation of tissue computed tomography number changes and dosimetric shifts after conventional whole-breast irradiation in patients undergoing breast-conserving surgery
Joo Hwan Lee, Dong Soo Lee, So Hyun Park, Young Kyu Lee, Jeong Soo Kim, Yong Seok Kim
Tumor Biology.2018; 40(8): 101042831879188. CrossRef - The influence of timing of radiation therapy following breast-conserving surgery on 10-year disease-free survival
Marissa C van Maaren, Reini W Bretveld, Jan J Jobsen, Renske K Veenstra, Catharina GM Groothuis-Oudshoorn, Hendrik Struikmans, John H Maduro, Luc JA Strobbe, Philip MP Poortmans, Sabine Siesling
British Journal of Cancer.2017; 117(2): 179. CrossRef
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Circulating Plasma Biomarkers for TSU-68, an Oral Antiangiogenic Agent, in Patients with Metastatic Breast Cancer
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Changhoon Yoo, Sung-Bae Kim, Jungsil Ro, Seock-Ah Im, Young-Hyuck Im, Jee Hyun Kim, Jin-Hee Ahn, Kyung Hae Jung, Hong Suk Song, Seok Yun Kang, Hee Sook Park, Hyun-Cheol Chung
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Cancer Res Treat. 2016;48(2):499-507. Published online July 14, 2015
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DOI: https://doi.org/10.4143/crt.2015.089
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Abstract
PDFPubReaderePub
- Purpose
This study analyzed the role of plasma biomarkers for TSU-68 in a previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in patients with metastatic breast cancer.
Materials and Methods
A total of 77 patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39 in the docetaxel alone arm). Blood samples were collected prior to the start of each cycle, and vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)- AA, -AB, -BB, fibroblast growth factor, M30, C-reactive protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked immunosorbent assay. The primary endpoint was progression-free survival (PFS).
Results
In patients with baseline PDGF-AA ≥ median, median PFS was significantly worse in the TSU-68 plus docetaxel group than in the docetaxel alone group (5.4 months vs. 13.7 months, p=0.049), while a trend toward a PFS benefit was observed in those with baseline PDGF-AA < median (9.7 months vs. 4.0 months, p=0.18; p for interaction=0.03). In the TSU-68 plus docetaxel group, PFS showed significant association with fold changes in CRP (p=0.001), IL-6 (p < .001), PDGF-BB (p=0.02), and VEGF (p=0.047) following the first treatment cycle.
Conclusion
Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6 levels were predictive for the efficacy of TSU-68.
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Impact of Molecular Subtype Conversion of Breast Cancers after Neoadjuvant Chemotherapy on Clinical Outcome
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Siew Kuan Lim, Moo Hyun Lee, In Hae Park, Ji Young You, Byung-Ho Nam, Byeong Nam Kim, Jungsil Ro, Keun Seok Lee, So-Youn Jung, Young Mee Kwon, Eun Sook Lee
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Cancer Res Treat. 2016;48(1):133-141. Published online April 7, 2015
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DOI: https://doi.org/10.4143/crt.2014.262
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Abstract
PDFPubReaderePub
- Purpose
The aim of this study was to examine molecular subtype conversions in patients who underwent neoadjuvant chemotherapy (NAC) and analyze their clinical implications.
Materials and Methods
We included consecutive breast cancer patients who received NAC at the National Cancer Center, Korea, between August 2002 and June 2011, and had available data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor status prior to NAC. Molecular subtypes, hormone receptor (HR) status, and ER and PR Allred scores before and after NAC were compared, and the long-term outcomes were analyzed.
Results
Of 322 patients, 32 (9.9%) achieved a pathologic complete response after NAC. HR+/HER2– tumors tended to convert into triple negative (TN) tumors (10.3%), whereas 34.6% of TN tumors gained HR positivity to become HR+/HER2– tumors. Clinical outcomes of molecular subtype conversion groups were compared against patients who remained as HR+/HER2– throughout. The HR+/HER2– to TN group had significantly poorer recurrencefree survival (RFS) (hazard ratio, 3.54; 95% confidence interval [CI], 1.60 to 7.85) and overall survival (OS) (hazard ratio, 3.73; 95% CI, 1.34 to 10.38). Patients who remained TN throughout had the worst outcomes (for RFS: hazard ratio, 3.70; 95% CI, 1.86 to 7.36; for OS: hazard ratio, 5.85; 95% CI, 2.53 to 13.51), while those who converted from TN to HR+/HER2– showed improved comparable survival outcomes.
Conclusion
Molecular subtypes of breast cancers changed frequently after NAC, resulting in different tumor prognostication. Tumor subtyping should be repeated after NAC in patients with breast cancer.
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Breast Cancer–Related Lymphedema after Neoadjuvant Chemotherapy
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Myungsoo Kim, In Hae Park, Keun Seok Lee, Jungsil Ro, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Eun Sook Lee, Tae Hyun Kim, Kwan Ho Cho, Kyung Hwan Shin
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Cancer Res Treat. 2015;47(3):416-423. Published online November 17, 2014
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DOI: https://doi.org/10.4143/crt.2014.079
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Abstract
PDFPubReaderePub
- Purpose
The risk for lymphedema (LE) after neoadjuvant chemotherapy (NCT) in breast cancer patients has not been fully understood thus far. This study is conducted to investigate the incidence and time course of LE after NCT. Materials and Methods A total of 313 patients with clinically node-positive breast cancer who underwent NCT followed by surgery with axillary lymph node (ALN) dissection from 2004 to 2009 were retrospectively analyzed. All patients received breast and supraclavicular radiation therapy (SCRT). The determination of LE was based on both objective and subjective methods, as part of a prospective database. Results At a median follow-up of 5.6 years, 132 patients had developed LE: 88 (28%) were grade 1; 42 (13%) were grade 2; and two (1%) were grade 3. The overall 5-year cumulative incidence of LE was 42%. LE first occurred within 6 months after surgery in 62%; 1 year in 77%; 2 years in 91%; and 3 years in 96%. In a multivariate analysis, age (hazard ratio [HR], 1.66; p < 0.01) and the number of dissected ALNs (HR, 1.68; p < 0.01) were independent risk factors for LE. Patients with both of these risk factors showed a significantly higher 5-year cumulative incidence of LE compared with patients with no or one risk factor (61% and 37%, respectively; p < 0.001). The addition of adjuvant chemotherapy did not significantly correlate with LE. Conclusion LE after NCT, surgery, and SCRT developed early after treatment, and with a high incidence rate. More frequent surveillance of arm swelling may be necessary in patients after NCT, especially during the first few years of follow-up.
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Breast Cancer Research and Treatment.2024; 204(2): 223. CrossRef - Incidence and risk factors of breast cancer-related lymphedema in Korea: A nationwide retrospective cohort study
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Gunel Guliyeva, Maria T. Huayllani, Daniel Boczar, Francisco R. Avila, Xiaona Lu, Antonio Jorge Forte
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Aomei Shen, Qian Lu, Xin Fu, Xiaoxia Wei, Liyuan Zhang, Jingru Bian, Wanmin Qiang, Dong Pang
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Healthcare.2023; 11(13): 1833. CrossRef - Discussion: Variable Anatomy of the Lateral Upper Arm Lymphatic Channel: An Anatomical Risk Factor for Breast Cancer–Related Lymphedema
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Prognostic Role of Interleukin-6, Interleukin-8, and Leptin Levels According to Breast Cancer Subtype
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Young Ae Cho, Mi-Kyung Sung, Jee-Young Yeon, Jungsil Ro, Jeongseon Kim
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Cancer Res Treat. 2013;45(3):210-219. Published online September 30, 2013
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DOI: https://doi.org/10.4143/crt.2013.45.3.210
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Abstract
PDFPubReaderePub
- PURPOSE
Inflammation within the tumor microenvironment has been reported to show an association with poor prognosis in breast cancer. However, the associations may differ according to breast cancer subtype. In this study, we investigated the association between inflammation-related markers and breast cancer recurrence according to patients' tumor subtypes.
MATERIALS AND METHODS
This prospective study included 240 patients who underwent surgery for management of newly diagnosed breast cancer. Levels of inflammation-related markers (interleukin [IL]-1beta, IL-6, IL-8, monocyte chemoattractant protein-1 [MCP-1], leptin, and adiponectin) were measured at diagnosis, and the associations between these markers and breast cancer recurrence during a six-year follow-up period were examined using the Kaplan-Meier statistical method.
RESULTS
Overall, inflammation-related markers showed no association with breast cancer recurrence. However, when data were stratified by tumor subtype, higher levels of some mediators showed an association with poor prognosis among patients with particular subtypes. Compared to patients without recurrence, patients with recurrence had higher levels of circulating IL-6 (p=0.024) and IL-8 (p=0.016) only among those with HER2- tumors and had higher levels of leptin (p=0.034) only among those with estrogen receptor (ER)+/progesterone receptor (PR)+ tumors. Results of survival analyses revealed an association of high levels of IL-6 (p=0.016) and IL-8 (p=0.022) with poor recurrence-free survival in patients with HER2- tumors. In addition, higher leptin levels indicated shorter recurrence-free survival time only among patients with ER+/PR+ tumors (p=0.022).
CONCLUSION
We found that certain cytokines could have a differential prognostic impact on breast cancer recurrence according to breast cancer subtype. Conduct of additional large studies will be required in order to elucidate the precise roles of these cytokines in breast cancer progression.
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Citations
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Guillaume Desmarais, Gabriel Charest, Hélène Therriault, Minghan Shi, David Fortin, Rachel Bujold, David Mathieu, Benoit Paquette
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Cesar Augusto Santa-Maria, Jingsheng Yan, Xian-Jin Xie, David Michael Euhus
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Ilais Moreno Velásquez, Johan Ärnlöv, Karin Leander, Lars Lind, Bruna Gigante, Axel C. Carlsson
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Kingsley O. Osuala, Mansoureh Sameni, Seema Shah, Neha Aggarwal, Michelle L. Simonait, Omar E. Franco, Yan Hong, Simon W. Hayward, Fariba Behbod, Raymond R. Mattingly, Bonnie F. Sloane
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Zach S. Templeton, Wen-Rong Lie, Weiqi Wang, Yael Rosenberg-Hasson, Rajiv V. Alluri, John S. Tamaresis, Michael H. Bachmann, Kitty Lee, William J. Maloney, Christopher H. Contag, Bonnie L. King
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ShuChen Lin, ZhiHua Gan, Kun Han, Yang Yao, DaLiu Min
Tumori Journal.2015; 101(5): 535. CrossRef
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A Case of Locally Advanced Breast Cancer Complicated by Pulmonary Tumor Thrombotic Microangiopathy
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Hak Jin Kim, Mi Hyang Kwak, Sun-Young Kong, Moon-Woo Seong, Han-Sung Kang, Keun Seok Lee, Jungsil Ro
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Cancer Res Treat. 2012;44(4):267-270. Published online December 31, 2012
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DOI: https://doi.org/10.4143/crt.2012.44.4.267
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Abstract
PDFPubReaderePub
- Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare, malignancy-related complication that causes marked pulmonary hypertension, right heart failure, and death. We report on a patient with locally advanced breast cancer whose course was complicated by fatal PTTM based on clinical and laboratory findings.
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Citations
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Rohit H. Godbole, Rajan Saggar, Nader Kamangar
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M. Merad, A. Alibay, S. Ammari, S. Antoun, A. Bouguerba, S. Ayed, F. Vincent
Revue des Maladies Respiratoires.2017; 34(10): 1045. CrossRef - Ante-mortem diagnosis of pulmonary tumour thrombotic microangiopathy in a patient with unrecognised extramammary Paget's disease
Aya Banno, Keijiro Chiba, Hiroko Kasai, Keiichi Nagami
BMJ Case Reports.2016; : bcr2016216666. CrossRef - Pulmonary Tumor Thrombotic Microangiopathy Associated with Advanced Gastric Cancer Successfully Treated with Chemotherapy
Seung-Hyun Yoo, Kwonoh Park, Ji Yeon Hong, Ji Yeon Kim, Jang Won Park, Yong Won Park, Kyung-Hun Lee, Kyung-So Jeon
The Ewha Medical Journal.2014; 37(2): 146. CrossRef - A Case of Pulmonary Tumor Thrombotic Microangiopathy Diagnosed by Transbronchial Lung Biopsy and Treated with Chemotherapy and Long-Term Oxygen and Anticoagulation Therapies
Atsushi Kitamura, Naoki Nishimura, Torahiko Jinta, Rika Suda, Yasuhiko Yamano, Genta Ishikawa, Yutaka Tomishima, Tsuyoshi Hamaoka, Koyu Suzuki, Naohiko Chohnabayashi
Case Reports in Pulmonology.2013; 2013: 1. CrossRef
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Serum HER2 as a Response Indicator to Various Chemotherapeutic Agents in Tissue HER2 Positive Metastatic Breast Cancer
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Sun-Young Kong, Do Hoon Lee, Eun Sook Lee, Susan Park, Keun Seok Lee, Jungsil Ro
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Cancer Res Treat. 2006;38(1):35-39. Published online February 28, 2006
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DOI: https://doi.org/10.4143/crt.2006.38.1.35
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Abstract
PDFPubReaderePub
- Purpose
The aim of study was to evaluate the usefulness of serum HER2 as a therapeutic response indicator in patients with HER2 positive metastatic breast cancer (MBC). Materials and MethodsThe levels of serum HER2 and CA15.3 were assayed in 148 serial serum samples from 50 HER2 positive MBC patients at both the baseline and follow-ups. The changes in the levels of serum HER2 and CA15.3 in relation to the tumor responses to the various chemotherapy regimens were monitored. ResultsThe levels of serum HER2 and CA15.3 were elevated in 82% and 62% of tissue HER2 positive patients, respectively, prior to therapies, with the changes in both tumor markers showing statistical significance in relation to the tumor responses (p<0.01) in patients with elevated baseline serum markers. ConclusionThe level of serum HER2 could be a valuable response indicator, not only for trastuzumab containing therapy, but also for other common MBC chemotherapeutic agents. Also, as it is more frequently elevated, the serum level of HER2 may also be a more useful tumor marker than CA15.3 in HER2 positive MBC.
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Citations
Citations to this article as recorded by - AlGaN/GaN HEMT Based Biosensor for Detection of the HER2 Antigen Spiked in Human Serum
Shivanshu Mishra, Pharyanshu Kachhawa, Prasenjit Mondal, Surajit Ghosh, Chaturvedula Tripura, Nidhi Chaturvedi
IEEE Transactions on Electron Devices.2022; 69(8): 4527. CrossRef - Amphiregulin confers trastuzumab resistance via AKT and ERK activation in HER2-positive breast cancer
Ji-Won Kim, Debora K. Kim, Ahrum Min, Kyung-Hun Lee, Hyun-Jin Nam, Jee Hyun Kim, Jin-Soo Kim, Tae-Yong Kim, Seock-Ah Im, In Ae Park
Journal of Cancer Research and Clinical Oncology.2016; 142(1): 157. CrossRef - The Significance of Serum HER2 Levels at Diagnosis on Intrinsic Subtype-Specific Outcome of Operable Breast Cancer Patients
Moo Hyun Lee, So-Youn Jung, Sun Hee Kang, Eun Jin Song, In Hae Park, Sun-Young Kong, Young Mee Kwon, Keun Seok Lee, Han-Sung Kang, Eun Sook Lee, Aamir Ahmad
PLOS ONE.2016; 11(10): e0163370. CrossRef - HER2 amplification level is not a prognostic factor for HER2-positive breast cancer with trastuzumab-based adjuvant treatment: a systematic review and meta-analysis
Qian-Qian Xu, Bo Pan, Chang-Jun Wang, Yi-Dong Zhou, Feng Mao, Yan Lin, Jing-Hong Guan, Song-Jie Shen, Xiao-Hui Zhang, Ya-Li Xu, Ying Zhong, Xue-Jing Wang, Yan-Na Zhang, Qiang Sun
Oncotarget.2016; 7(39): 63571. CrossRef - Serum HER2 levels are increased in cats with mammary carcinomas and predict tissue HER2 status
Maria Soares, Rita Ribeiro, Shabir Najmudin, Andreia Gameiro, Rita Rodrigues, Fátima Cardoso, Fernando Ferreira
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Jingchun Sun, Kevin Zhu, W Jim Zheng, Hua Xu
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Yukun Chen, Jingchun Sun, Liang-Chin Huang, Hua Xu, Zhongming Zhao
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Ji-Won Kim, Jee Hyun Kim, Seock-Ah Im, Yu Jung Kim, Hye-Suk Han, Jin-Soo Kim, Sae-Won Han, Yoon Kyung Jeon, Do-Youn Oh, Wonshik Han, Tae-You Kim, In Ae Park, Dong-Young Noh, Yung-Jue Bang
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Guodong Shen, Hui Huang, Anli Zhang, Ting Zhao, Siyi Hu, Liansheng Cheng, Jing Liu, Weihua Xiao, Bin Ling, Qiang Wu, Lihua Song, Wei Wei
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PLoS ONE.2011; 6(4): e18764. CrossRef
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The Survival and Financial Benefit of Investigator-Initiated Trials Conducted by Korean Cancer Study Group
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Bum Jun Kim, Chi Hoon Maeng, Bhumsuk Keam, Young-Hyuck Im, Jungsil Ro, Kyung Hae Jung, Seock-Ah Im, Tae Won Kim, Jae Lyun Lee, Dae Seog Heo, Sang-We Kim, Keunchil Park, Myung-Ju Ahn, Byoung Chul Cho, Hoon-Kyo Kim, Yoon-Koo Kang, Jae Yong Cho, Hwan Jung Yun, Byung-Ho Nam, Dae Young Zang
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Received April 30, 2024 Accepted July 8, 2024 Published online July 10, 2024
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DOI: https://doi.org/10.4143/crt.2024.421
[Epub ahead of print]
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Abstract
PDFPubReaderePub
- Purpose
The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients.
Materials and Methods
We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided.
Results
From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient.
Conclusion
Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.
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KCA
