Publications by authors named "Kuikui Jiang"

10 Publications

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BRAF V600E Mutation in Triple-Negative Breast Cancer: A Case Report and Literature Review.

Oncol Res Treat 2021 Nov 24:1-7. Epub 2021 Nov 24.

Department of Oncology, Sun Yat-Sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: The B-Raf proto-oncogene (BRAFV600E) gene mutation has been identified in a variety of malignancies, but no evidence of the efficacy of vemurafenib treatment in BRAFV600E mutant breast cancer (BC) has been reported.

Case Presentation: We reported a 60-year-old woman with confirmed triple-negative BC with BRAFV600E mutation. Progression-free survival (PFS) for first-line chemotherapy was 7 months. The patient received vemurafenib and albumin-bound paclitaxel as second-line therapy, exhibiting regression of some pulmonary metastatic lesions with concomitant progression of other lesions, and achieved 4.4 months of PFS. Genetic testing of the progressed pulmonary lesion revealed the BRAFV600E mutation, and acquired new mutations and AR amplification. The patient ultimately died of multiple organ failure and achieved 12 months of overall survival.

Conclusions: The BRAFV600E mutation may be a potential prognostic factor and therapeutic target for BC.
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http://dx.doi.org/10.1159/000520453DOI Listing
November 2021

Identification of a risk prediction model for clinical prognosis in HER2 positive breast cancer patients.

Genomics 2021 Oct 16;113(6):4088-4097. Epub 2021 Oct 16.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China. Electronic address:

Background New biomarkers are needed to identify different clinical outcomes for HER2+ breast cancer (BC). Methods Differential genes of HER2+ BC were screened based on TCGA database. We used WGCNA to identify the genes related to the survival. Genetic Algorithm was used to structure risk prediction model. The prognostic model was validated in GSE data. Results We constructed a risk prediction model of 6 genes to identify prognosis of HER2+ BC, including CLEC9A, PLD4, PIM1, PTK2B, AKNAD1 and C15orf27. Kaplan-Meier curve showed that the model effectively distinguished the survival of HER2+ BC patients. The multivariate Cox regression suggested that the risk model was an independent predictor for HER2+ BC. Analysis related to immune showed that significant differences in immune infiltration between high- and low-risk groups classified by the prognostic model. Conclusions Our study identified a risk prediction model of 6 genes that could distinguish the prognosis of HER2+ BC.
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http://dx.doi.org/10.1016/j.ygeno.2021.10.010DOI Listing
October 2021

Miller-Payne Grading and 70-Gene Signature Are Associated With Prognosis of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early-Stage Breast Cancer After Neoadjuvant Chemotherapy.

Front Oncol 2021 24;11:735670. Epub 2021 Sep 24.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Introduction: HR+/HER2- breast cancer (BC) has a much lower pathological complete response (pCR) rate to neoadjuvant chemotherapy (NAC). Therefore, to better stratify the relapse risk for HR+/HER2- non-pCR populations, it is essential to accurate identification new prognostic markers.

Materials And Methods: The study retrospectively analyzed 105 stage II-III patients who were diagnosed with HR+/HER2- BC and received NAC followed by breast and axilla surgery between 2013 and 2019 in Sun Yat-Sen University Cancer Center. The Miller-Payne (MP) grading system was used to evaluate pathological responses to NAC. The 70-gene signature was used to classify the prognosis signatures.

Results: Among the 105 patients, the study demonstrated that larger tumor size and lower progesterone receptor level at baseline and larger tumor size postoperative were statistically significantly associated with worse disease-free survival (DFS) ( = 0.004, = 0.021, and = 0.001, respectively). Among 54 patients who underwent the 70-gene assays, 26 (48.1%) had a low-risk signature; 28 (51.9%) patients had a high-risk signature. Patients with poor response (MP grades 1-2) were more likely to with a high-risk 70-gene signature than those with good response (MP grades 4-5). The final analysis showed that DFS was longer in the low-risk group than in the high-risk group [52.4 vs. 36.1 months of the median DFS, hazard ratio (HR) for recurrence, 0.29; 95% confidence interval (CI), 0.10-0.80; = 0.018]. DFS was longer in the good response (MP grades 3-4) group than in the poor response (MP grades 1-2) group (94.7% vs. 60% of the patients free from recurrence; HR, 0.16; 95% CI, 0.05-0.47; = 0.037). When stratified by MP grades combined with the 70-gene signature, subgroup analyses showed the good-response low-risk group with the best DFS, whereas the poor-response high-risk group showed the worst DFS ( = 0.048). Due to the short median follow-up time of 34.5 months (5.9-75.1 months), MP grades and the 70-gene signature did not show significant prognostic value for overall survival.

Conclusion: The study showed that analysis of MP grades combined with the 70-gene signature with residual NAC-resistant breast samples has a significant correlation with DFS.
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http://dx.doi.org/10.3389/fonc.2021.735670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498026PMC
September 2021

Establishment of Prognostic Nomograms for Predicting the Survival of HR-Positive, HER2-Negative Metastatic Breast Cancer Patients Treated with Everolimus.

Drug Des Devel Ther 2021 10;15:3463-3473. Epub 2021 Aug 10.

Departments of Medical Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.

Background: There are no clinically available prognostic models for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer treated with everolimus. We aimed to develop a tool to predict the progression-free survival (PFS) and overall survival (OS) of these patients and to identify optimal candidates who would benefit from everolimus-based treatment in this heterogeneous patient population.

Methods: The clinical data of patients with HR+, HER2- metastatic breast cancer receiving everolimus between May 2012 and January 2018 at Sun Yat-sen University Cancer Center were retrospectively retrieved. Based on potential prognostic factors derived from multivariate Cox analysis, we established predictive nomogram models for PFS and OS and evaluated their predictive values by means of the concordance index (C-index). Calibration curves were used to estimate the consistency between the actual observations and the nomogram-predicted probabilities.

Results: A total of 116 patients with HR+, HER2- metastatic breast cancer were enrolled in this study. Three independent prognostic factors, including the line of everolimus in the metastatic setting, everolimus clinical benefit rate and number of liver metastatic lesions, were identified from the multivariate Cox analysis. Prognostic models for individual survival prediction were established and graphically presented as nomograms. The C-index was 0.738 (95% confidence interval [CI]: 0.710-0.767) for the PFS nomogram and 0.752 (95% CI: 0.717-0.788) for the OS nomogram, which showed favourable discrimination. The calibration curves for the probabilities of 6-, 9-, and 12-month PFS and 1-, 2-, and 3-year OS suggested satisfactory consistency between the actual observations and the predicted probabilities.

Conclusion: We constructed convenient nomogram models for patients with HR+, HER2- metastatic breast cancer to individually predict their potential benefits from everolimus in the metastatic setting. The models showed good performance in terms of accuracy, discrimination capacity and clinical application value.
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http://dx.doi.org/10.2147/DDDT.S314723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364432PMC
August 2021

Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer: An open-label, dose-escalation, phase I study.

Cancer Commun (Lond) 2021 02 2;41(2):171-182. Epub 2021 Feb 2.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China.

Background: The introductions of anti- human epidermal growth factor receptor-2 (HER2) agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer. BAT8001 is a novel antibody-drug conjugate targeting human epidermal growth factor receptor-2 (HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine. This dose-escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.

Methods: This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21-day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective.

Results: Between March 2017 to May 2018, 29 HER2-positive breast cancer patients were enrolled. The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ-glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%-61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%-94.2%) patients.

Conclusions: BAT8001 demonstrated favorable safety profiles, with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.
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http://dx.doi.org/10.1002/cac2.12135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896747PMC
February 2021

Identification and characterization of critical genes associated with tamoxifen resistance in breast cancer.

PeerJ 2020 4;8:e10468. Epub 2020 Dec 4.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: Tamoxifen resistance in breast cancer is an unsolved problem in clinical practice. The aim of this study was to determine the potential mechanisms of tamoxifen resistance through bioinformatics analysis.

Methods: Gene expression profiles of tamoxifen-resistant MCF-7/TR and MCF-7 cells were acquired from the Gene Expression Omnibus dataset GSE26459, and differentially expressed genes (DEGs) were detected with R software. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was generated, and we analyzed hub genes in the network with the Search Tool for the Retrieval of Interacting Genes database. Finally, we used siRNAs to silence the target genes and conducted the MTS assay.

Results: We identified 865 DEGs, 399 of which were upregulated. GO analysis indicated that most genes are related to telomere organization, extracellular exosomes, and binding-related items for protein heterodimerization. PPI network construction revealed that the top 10 hub genes-, and -might be associated with tamoxifen resistance. Consistently, RT-qPCR analysis indicated that the expression of these 10 genes was increased in MCF-7/TR cells comparing with MCF-7 cells. Four hub genes ( and ) were related to overall survival in patients who accepted tamoxifen. In addition, knockdown of HSPH1 by siRNA may lead to reduced growth of MCF-7/TR cell with a trend close to significance ( = 0.07), indicating that upregulation of HSPH1 may play a role in tamoxifen resistance.

Conclusion: This study revealed a number of critical hub genes that might serve as therapeutic targets in breast cancer resistant to tamoxifen and provided potential directions for uncovering the mechanisms of tamoxifen resistance.
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http://dx.doi.org/10.7717/peerj.10468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720728PMC
December 2020

Metronomic chemotherapy of cyclophosphamide plus methotrexate for advanced breast cancer: Real-world data analyses and experience of one center.

Cancer Commun (Lond) 2020 05 11;40(5):222-233. Epub 2020 May 11.

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.

Background: Real-world data of the CM regimen [cyclophosphamide (CTX) plus methotrexate (MTX)] in metronomic pattern for advanced breast cancer is limited to small-sample or retrospective studies. This study was aimed to determine the effectiveness and safety of CM regimen in treating advanced breast cancer and to identify which patients are most likely to benefit from metronomic CM regimen.

Methods: Patients with advanced breast cancer who received the metronomic CM regimen at least once between January 2009 and February 2019 in Sun Yat-sen University Cancer Center were included. Clinicopathological characteristics were collected. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimates. Characteristics between patients with PFS < 6 months and ≥6 months were compared using the Chi-square test. Univariate and multivariate Cox regression model was used to estimate the prognostic factors for PFS and OS.

Results: A total of 186 patients were included. The median age and follow-up were 49 years and 13.3 months, respectively. Over 50% of the patients were estrogen receptor/progesterone receptor-positive, and 60.8% had been heavily treated (≥3 lines). The objective response rate was 3.8%, the disease control rate at 12 weeks was 41.4%, and the clinical benefit rate at 24 weeks was 31.2% (58/186). The median PFS was 4.0 months [95% confidence interval (CI): 3.6-4.7 months], the median duration of clinical benefit was 9.5 months (95% CI: 8.2-10.8 months), and the median OS was 26.8 months (95% CI: 20.9-37.7 months). Multivariate analysis for PFS revealed the CM regimen as maintenance therapy and no liver metastasis as favorable prognostic factors. Furthermore, patients without liver metastasis were more likely to have a PFS over 6 months than those with liver involvement (P = 0.022). Liver, lymph node, and brain metastases were unfavorable prognostic factors for OS. The CM regimen was well-tolerated without newly reported adverse events.

Conclusions: The CM regimen was effective in selected patients. In clinical practice, it would be better used as maintenance therapy and in patients without liver metastasis. Further follow-up investigation should be performed to examine its effect when used in combination with other treatments and determine predictive biomarkers.
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http://dx.doi.org/10.1002/cac2.12029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238669PMC
May 2020

Administration of Lapatinib with Food Increases Its Plasma Concentration in Chinese Patients with Metastatic Breast Cancer: A Prospective Phase II Study.

Oncologist 2020 09 14;25(9):e1286-e1291. Epub 2020 Feb 14.

Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Lessons Learned: Administration of lapatinib with food significantly increased its plasma concentration in Chinese patients with metastatic breast cancer. There were no serious adverse events during the study and no significant differences in lapatinib-related adverse events between the fasted and fed states.

Background: Lapatinib, a small molecular reversible dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth receptor 2 (HER2), was approved for use in combination with capecitabine to treat metastatic HER2-positive breast cancer. Administration of lapatinib in the fasted state was recommended; however, our preliminary phase II trial data showed that administration of lapatinib with food increased its concentration.

Methods: This study was a single-center, open-label, and prospective self-controlled clinical study. Ten Chinese patients with metastatic breast cancer were enrolled from June 2017 to April 2018. They were required to receive lapatinib plus physician's choice of chemotherapy. Patients were required to take lapatinib orally on an empty stomach continually for 10 days, and then take lapatinib with food continually for the next 10 days. Plasma concentration was measured by liquid chromatography on the 9th and 10th day of each state.

Results: Area under the concentration-time curve (AUC) of the fasted state and the fed state was 21.23 ± 8.91 mg*h/L (coefficient of variation (CV)% 42%) and 60.60 ± 16.64 mg*h/L (CV% 27%), respectively. The mean plasma concentration in the fasted state was 0.88 ± 0.39 mg/L (CV% 45%), and that in the fed state was 2.53 ± 0.77 mg/L (CV% 30%). Compared with taking lapatinib on an empty stomach, receiving lapatinib with food significantly increased the plasma concentration of lapatinib (Wilcoxon match-paired test, p = .005). In addition, there were no serious adverse events during the study or significant difference in lapatinib-related adverse events between the two states.

Conclusion: Our study shows that receiving lapatinib with food can increase its plasma concentration with no significantly increased drug-related toxicity. We suggest that a larger-sample-size clinical trial is needed to fully understand the effect of administration of lapatinib with food.
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http://dx.doi.org/10.1634/theoncologist.2020-0044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485350PMC
September 2020

Pretreatment anti-Mullerian hormone-based nomogram predicts menstruation status after chemotherapy for premenopausal women with hormone receptor-positive early breast cancer.

Breast Cancer Res Treat 2019 Feb 3;173(3):619-628. Epub 2018 Nov 3.

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Dongfeng Road East 651#, Guangzhou, 510060, China.

Purpose: Ovarian function is important for optimizing endocrine treatment in patients with hormone receptor-positive (HR+) early breast cancer (eBC). The aim of the study was to determine whether patients' pretreatment levels of anti-Mullerian hormone (AMH) were associated with menses status after chemotherapy and to build a predictive nomogram model for amenorrhea in women with HR+ eBC.

Methods: Between August 2013 and December 2014, 120 premenopausal patients with HR+ eBC were included retrospectively. The associations among age, prechemotherapy levels of AMH, follicle-stimulating hormone (FSH),and estradiol (E2) and the 2-year postchemotherapy menses status were analyzed. We determined the cutoff values of hormone levels by using the biostatistical tool (Cutoff Finder). A novel nomogram was established to predict the 2-year amenorrhea status based on the logistic analysis. Concordance index (C-index) was used to validate the capacity.

Results: One hundred nine women (90.8%) experienced amenorrhea after chemotherapy. AMH < 0.965 ng/ml predicted amenorrhea at 2 years (AUC 0.84, sensitivity 74% and specificity 81.8%), independent of age. The predictive nomogram based on age and pretreatment AMH and FSH levels was developed to predict the probability of 2-year postchemotherapy amenorrhea with a C-index of 0.88 (95% CI 0.84-0.91).

Conclusions: In premenopausal patients with HR+ eBC, prechemotherapy AMH concentration was associated with the patient's 2-year amenorrhea status, independent of age. The nomogram model based on age and pretreatment AMH and FSH levels accurately predicted the 2-year amenorrhea status.
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http://dx.doi.org/10.1007/s10549-018-4997-2DOI Listing
February 2019

Tracheal microenvironment, ANP metabolism and airway tone.

Sci Bull (Beijing) 2016 22;61(20):1551-1554. Epub 2016 Sep 22.

Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100032 China.

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http://dx.doi.org/10.1007/s11434-016-1170-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075019PMC
September 2016
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