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Статті в журналах з теми "San jun yi zhang dui"
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Ji, Yinghua, Honglan Qu, Feidu Zhou, Juan Wang, Qianfu Wu, Guohua Dai, Mengyou Liu, et al. "Abstract PO2-16-08: Adjuvant Treatment Selection for County-Level Patients with HR+/HER2- Early Breast Cancer in a Real-Life Setting in China." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO2–16–08—PO2–16–08. http://dx.doi.org/10.1158/1538-7445.sabcs23-po2-16-08.
Повний текст джерелаАнотація:
Abstract Background: CHASE001 (NCT05544123), a prospective, non-interventional multicenter study exploring real-world treatment and referral behavior of Chinese county patients (pts) with HER2+ or HR+/HER2– breast cancer is ongoing since September 2022. A prespecified interim analysis (IA) on 750 HER2+ and HR+/HER2- early breast cancer (eBC) was reported at the ESMO Congress 2023. In the 2nd IA from CHASE001, adjuvant treatment selection for patients with HR+/HER2- eBC will be evaluated. Methods: The study was designed to enroll 2500 pts, including four cohorts (HER2+ eBC, HR+/HER2-eBC, HER2+ advanced BC, and HR+/HER2- aBC). In this IA, HR+/HER2- eBC pts after surgery were included. Descriptive statistics reported patient demographics, clinical and disease characteristics and treatment patterns. To investigate the factors associated with chemotherapy-free regimen, non-anthracycline chemotherapy regimen and ovarian function suppression (OFS), univariate and multivariate logistic regression analyses were conducted. Results: At data cutoff (May 17, 2023), 697 HR+/HER2- eBC pts (median age 52 years, 45.77% pT2, 50.93% pN0, 56.10% G2) were included from 26 institutions in China county areas, 338 (48.49%) were premenopausal. 584 (83.79%) received adjuvant chemotherapy, with a few (47/584, 8.05%) initially developing their treatment plan at a higher level hospital (national or provincial tertiary hospital). AC-T (309/584, 52.91%) was the most commonly used regimen. 181 (30.99%) pts received non-anthracycline chemotherapy regimen (mainly TC), and pts with N0, age≥65 years and ki67 < 20% had the strongest association to this regimen (multivariate OR=0.082, 95%CI [0.037,0.179], OR=0.463, 95%CI [0.250,0.859], and OR=0.642, 95%CI [0.418,0.985], respectively). Interestingly, on univariate analysis pts initially diagnosed in a higher level hospital were significantly associated with non-anthracycline regimen (P=0.0109), however on multivariate analysis it was no longer significant. 483 pts received endocrine therapy, including 234 (48.45%) premenopausal pts. The most commonly used endocrine regimen for premenopausal pts was OFS/OFS+ (122/234, 52.14%) ,of which half (61, 50%) were prescribed OFS+TAM/TOR; followed by TAM/TOR monotherapy (69/234, 29.49%). The proportions of patients classified as low, intermediate, and high clinical risk for recurrence (investigator assessed)were 33.62%, 42.67% and 23.71%. The OFS rate were 39.74% in low, 61.62% in intermediate and 70.91% in high risk pts, respectively. Multivariable analyses found that high clinical risk, age < 45 years and ki67 < 20% were strongly associated with the use of OFS (OR=0.210, 95%CI [0.066,0.674], OR=0.327, 95%CI [0.165,0.649], and OR=0.405, 95%CI [0.194,0.845], respectively). For postmenopausal pts, AI monotherapy (84.74%) was the most commonly used endocrine regimen. Conclusions: To our knowledge, this is the first real-world study evaluating the treatment patterns and referral behavior of BC pts in China counties. The 2nd IA results presented showed the current systemic adjuvant treatment preferences and influence factors from a large sample of HR+/HER2- eBC pts in China counties, which were generally consistent with China BC treatment guidelines. Table 1. Utilization of adjuvant systemic therapy regimens in 697 HR+/HER2− eBC pts, China counties AC-T: (dd)doxorubicin/epirubicin, cyclophosphamide, followed by (dd)paclitaxel/docetaxel; TC: paclitaxel/docetaxel, cyclophosphamide; AC: doxorubicin/epirubicin, cyclophosphamide; TAC: docetaxel, doxorubicin/epirubicin, cyclophosphamide; TAM: tamoxifen; OFS: ovarian function suppression; AI: aromatase inhibitors; TOR: toremifene; CDK4/6i: cyclin-dependent kinase 4/6 inhibitors; “Other” category includes various therapies used in <1% of patients each Citation Format: Yinghua Ji, Honglan Qu, Feidu Zhou, Juan Wang, Qianfu Wu, Guohua Dai, Mengyou Liu, Wenbo He, Wei Liang, Qiuli Meng, Yun Ren, Guoxiang Luo, Hongjian Wang, Hui Liu, Zien Qin, Yingguo Tian, Huali Tang, Hongmei Liu, Jun Luo, Zengfeng Yu, Guinv Hu, Jianzhi Gao, Xiang Tan, Yi Liu, Yuanjiang Zhang, Ming Wang, Min Zhang, Ping Lu. Adjuvant Treatment Selection for County-Level Patients with HR+/HER2- Early Breast Cancer in a Real-Life Setting in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-08.
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Wan, Rui, Yi Fung Chau, Jun Zhao, Zhe Liu, Mingfang Zhao, Yanqiu Zhao, Xiumei Dai, et al. "Abstract CT055: Efficacy of YK-029A, a novel EGFR TKI, in advanced NSCLC patients with acquired T790M mutation." Cancer Research 84, no. 7_Supplement (April 5, 2024): CT055. http://dx.doi.org/10.1158/1538-7445.am2024-ct055.
Повний текст джерелаАнотація:
Abstract In the multicenter, dose-escalation and dose-expansion phase 1 clinical trial (NCT05767866), we evaluated safety and tolerability of YK-029A in various EGFR mutated non-small-cell lung cancer (NSCLC). We have reported efficacy of YK-029A in untreated NSCLC with EGFR ex20ins mutation[1]. This time we report efficacy of YK-029A in patients with acquired EGFR T790M mutation after failure of first or second generation EGFR tyrosine kinase inhibitors (TKIs). Method: This dose-escalation and dose-expansion phase 1 trial recruited previously treated NSCLC patients with EGFR T790M mutation or patients with EGFR ex20ins or EGFR rare mutations. In dose-escalation phase, patients with EGFR T790M mutation were enrolled. YK-029A was given at doses of 50, 100, 150, 200 to 250 mg/day (3+3 design). In dose-expansion phase, patients with EGFR T790M, EGFR ex20ins, or EGFR rare mutations were enrolled. The primary objective was safety. Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) were explored. Efficacy of YK-029A in EGFR T790M mutated NSCLC was assessed by the investigators. Results: A total of 114 patients were recruited into the study. Safety profile of the first 108 patients was reported previously[1]. By the cut-off date on Sep 12, 2023, 38 patients harbored EGFR T790M mutation were included in efficacy analysis. All these patients were previously treated with first or second generation EGFR-TKIs. The objective response rate (ORR; RECIST 1.1) was 65.8% (95%CI: 48.6%-80.4%) and disease control rate (DCR) was 84.2% (95%CI: 68.7%-94.0%). With a median follow-up time of 8.2 months,the median progression free survival (PFS) was 11.0 months (95%CI: 7.75-NR). The median overall survival (OS) was not reached. Among the 8 patients with measurable brain metastases, intracranial ORR was 75% (95%CI: 35.6%-95.6%) . Conclusions: YK-029A has promising activity in previously treated NSCLC patients harboring EGFR T790M mutation. Reference[1] DUAN J, WU L, YANG K, et al. Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK-029A in Treatment-Naive Patients With Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations: A Phase 1 Trial [J]. J Thorac Oncol, 2023. Citation Format: Rui Wan, Yi Fung Chau, Jun Zhao, Zhe Liu, Mingfang Zhao, Yanqiu Zhao, Xiumei Dai, Yueyin Pan, Zhihong Zhang, Yu Yao, Kunyu Yang, Lin Wu, Yanyan Xie, Bi Chen, Yixuan Yang, Yongqi Guo, Jie Wang, Jianchun Duan. Efficacy of YK-029A, a novel EGFR TKI, in advanced NSCLC patients with acquired T790M mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT055.
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Lin, Jia-Yi, Wei-Wei Zhang, Qing-Jie Li, Xue-Liang Fang, Jun-Yan Li, Shi-Wei He, Ying-Qin Li, et al. "Abstract 1113: USP18 impairs the sensitivity of radiotherapy for nasopharyngeal carcinoma by promoting the ubiquitination and nuclear translocation of TRIM29." Cancer Research 84, no. 6_Supplement (March 22, 2024): 1113. http://dx.doi.org/10.1158/1538-7445.am2024-1113.
Повний текст джерелаАнотація:
Abstract Radiotherapy is the main and preferred treatment for nasopharyngeal carcinoma (NPC), owing to its high sensitivity to radiation. However, there are ~20% patients suffering from tumor recurrence. Accumulating evidences show that protein ubiquitination plays a vital role in radiation caused DNA damage response. Here, we identified that the deubiquitinase USP18 is highly expressed in NPC tissues, and inversely associated with radiosensitivity of NPC cells. USP18 interacts with TRIM29 and promotes its K27-linked ubiquitination independent of its deubiquitinase activity. Further investigation reveals that USP18 acts as a scaffold to recruit the E3 ubiquitin ligase TRIM21 to directly ubiquitinate TRIM29 at Lys307, thus promoting its oligomerization and nuclear translocation, and thereby facilitates the DNA damage repair of NPC cells after irradiation. Clinically, higher expression of USP18 indicates poor response to radiotherapy and worse prognosis in NPC patients. Our findings reveal the critical role of USP18 in regulating radiosensitivity, and targeting USP18-TRIM21-TRIM29 axis maybe a novel strategy to synergize with radiotherapy for NPC patients. Citation Format: Jia-Yi Lin, Wei-Wei Zhang, Qing-Jie Li, Xue-Liang Fang, Jun-Yan Li, Shi-Wei He, Ying-Qin Li, Jun Ma, Na Liu, Yin Zhao, Rui Guo. USP18 impairs the sensitivity of radiotherapy for nasopharyngeal carcinoma by promoting the ubiquitination and nuclear translocation of TRIM29 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1113.
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Shi, Qiyun, Xiaowei Qi, Peng Tang, Linjun Fan, Li Chen, Shushu Wang, Guozhi Zhang, et al. "Abstract OT2-22-01: Epirubicin, cyclophosphamide and pyrotinib followed by docetaxel, trastuzumab and pyrotinib as neoadjuvant therapy for stage II-III HER2-positive breast cancer: a single-arm, multicenter phase 2 trial." Cancer Research 83, no. 5_Supplement (March 1, 2023): OT2–22–01—OT2–22–01. http://dx.doi.org/10.1158/1538-7445.sabcs22-ot2-22-01.
Повний текст джерелаАнотація:
Abstract Background: Dual HER2 targeted therapy with pyrotinib (a tyrosine kinase inhibitor targeting HER1, HER2, and HER4) and trastuzumab plus chemotherapy has been approved as neoadjuvant therapy for patients with HER2-positive breast cancer in China based on the results from phase 3 PHEDRA study. However, the optimal chemotherapy partner still needs exploration. This multicenter phase 2 trial (ChiCTR1900022293) aimed to investigate the efficacy and safety of epirubicin, cyclophosphamide and pyrotinib followed by docetaxel, trastuzumab and pyrotinib (ECP-THP) as neoadjuvant therapy for patients with stage II-III HER2-positive breast cancer. Methods: Patients received intravenous epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for four 21-day cycles, followed by intravenous docetaxel (75 mg/m2) and trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg) on day 1 for 4 cycles. Pyrotinib 400 mg was given orally once daily throughout the neoadjuvant therapy period. Surgery was performed within 16-20 days after the last neoadjuvant therapy. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate. Results: Between May 2020 and May 2022, a total of 175 patients enrolled. As of May 31, 2022, 144 patients had undergone surgery; the median age was 51 years (range, 26-67). Sixty-seven (46.5%) of 144 patients had hormone receptor (HR)-negative disease, and 77 (53.5%) had HR-positive disease. The tpCR rate was 67.4% (97/144; 95%CI, 59.3%-74.5%). Patients with HR-negative disease had numerically higher tpCR rate than those with HR-positive disease (73.1% [95%CI, 61.5%-82.3%] vs. 62.3% [95%CI, 51.2%-72.3%]), but without statistical significance (P=0.230). Miller-Payne grade 4 and 5 pathological responses were found in 22 (15.3%) and 97 (67.4%) of 144 patients, respectively. Regarding clinical response to neoadjuvant therapy before surgery, 31 (21.5%) of 144 patients achieved complete response and 99 (68.8%) achieved partial response, with an objective response rate of 90.3% (95%CI, 84.3%-94.1%). Of 161 patients with available safety data, the most common grade ≥3 adverse events included diarrhea (57.1%), white blood cell count decreased (8.7%), and neutrophil count decreased (5.6%). No treatment-related deaths occurred. Conclusions: Patients with stage II-III HER2-positive breast cancer show favorable clinical and pathological response to this ECP-THP neoadjuvant regimen, with an acceptable safety profile. Citation Format: Qiyun Shi, Xiaowei Qi, Peng Tang, Linjun Fan, Li Chen, Shushu Wang, Guozhi Zhang, Mengyuan Wang, Hongying Che, Pengwei Lv, Dejie Chen, Jinhui Hu, Qiuyun Li, Yanwu Zhang, Qiao Yu, Kunxian Yang, Yuan Zhong, Chuang Chen, Zemin Zhou, Liyuan Qian, Jingwei Zhang, Mingde Ma, Yi Sun, Jiangbo Liu, Yi Zhang, Jun Jiang. Epirubicin, cyclophosphamide and pyrotinib followed by docetaxel, trastuzumab and pyrotinib as neoadjuvant therapy for stage II-III HER2-positive breast cancer: a single-arm, multicenter phase 2 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-22-01.
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Liang, Yan, Jing Liu, Tao Luo, Jia Ge, Hao Tian, Guozhi Zhang, Linjun Fan, et al. "Abstract P5-10-01: Phase 2 study of anlotinib combined with taxanes and lobaplatin in the neoadjuvant treatment of triple-negative breast cancer: efficacy, safety and biomarker analysis from the SWH-B006 (neoALTALL) trial." Cancer Research 83, no. 5_Supplement (March 1, 2023): P5–10–01—P5–10–01. http://dx.doi.org/10.1158/1538-7445.sabcs22-p5-10-01.
Повний текст джерелаАнотація:
Abstract Background: Anlotinib, a novel multi-target tyrosine kinase inhibitor that effectively inhibits VEGFR, PDGFR, FGFR, c-KIT, c-MET, and RET, monotherapy has been proven effective in HER-2 negative metastatic breast cancer, but its efficacy in early-stage triple-negative breast cancer (TNBC) is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients (pts) with primary TNBC. Methods: Pts with clinical stage II/III TNBC were to be treated with 5 cycles of anlotinib (12mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 or nab-paclitaxel 125 mg/m2, d1 and d8, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was pathological complete response (pCR) in the breast and axilla (tpCR; ypT0/is ypN0) and the secondary endpoints include pCR in the breast (bpCR; ypT0/is), event-free survival (EFS), invasive disease-free survival (iDFS), overall survival (OS), and safety. Exploratory study included biomarker analysis and efficacy comparation based on FUSCC classification (IHC-based). Results: From Jan 2021 to Feb 2022, a total of 24 pts were enrolled. The median age was 50 years (range, 26-64), 54% were postmenopausal, 75% were nodal involved, 29% had stage III, and 79% were Ki-67 high (≥30%). At the data cut off time of 30th Jun 2022, all 24 pts received at least one dose of study treatment and underwent surgery. Overall, 21 pts received five courses of anlotinib. Two pts discontinued anlotinb for safety reason, and one pt discontinued anlotinb due to missed dose in cycle 4. After surgery, 14 out of 24 pts achieved a tpCR (58.3%; 95% CI, 36.6%–77.9%), and the bpCR rate was also 58.3% (14/24). Of the 18 pts with the node-positive disease at diagnosis, 15/18 (83.3%) became ypN0. Based on the FUSCC IHC-based subtypes, the tpCR rates were 66.7% (6/9) for BLIS subtype, 80% (4/5) for IM subtype and 0% (0/4) for LAR subtype, respectively. Next-generation sequencing revealed that the most commonly mutated genes in these pts were TP53 (19/21, 90.5%), MYC (7/21, 33.3%), BRCA1 (5/21, 23.8%), PIK3CA (4/21, 19.0%), BCL2L11 (4/21, 19.0%), and RB1 (3/21, 14.3%). Subgroup analysis showed that the tpCR were 71.4% (5/7) and 42.9% (6/14) in MYC-amplified and wild-type pts, respectively, and 80% (4/5) and 43.8% (7/16) in BRCA1-mutated and wild-type pts, respectively. All of 24 pts in the safety population showed at least one treatment emergent adverse events (TEAEs). Grade 3 or 4 TEAEs occurred in 14 pts (58.3%), and the most common events were leucopenia (29.2%; n=7), neutropenia (29.2%; n=7), thrombocytopenia (20.8%; n=5), anemia (16.7%; n=4), hypertension (12.5%; n=3), and oral mucositis (8.3%; n=2), respectively. No treatment-related deaths occurred. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for pts with early-stage TNBC. The study is still ongoing, and the enrollment has been completed. Clinical trial information: ChiCTR2100043027. Funding: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. L. Corresponding author: Dr. Xiaowei Qi, qxw9908@foxmail.com. Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing. Citation Format: Yan Liang, Jing Liu, Tao Luo, Jia Ge, Hao Tian, Guozhi Zhang, Linjun Fan, Lin Ren, Li Chen, Peng Tang, Kai Zhu, Xiuwu Bian, Jun Jiang, Yi Zhang, Xiaowei Qi, Peng Tang, Kai Zhu, Xiuwu Bian, Jun Jiang, Yi Zhang, Xiaowei Qi. Phase 2 study of anlotinib combined with taxanes and lobaplatin in the neoadjuvant treatment of triple-negative breast cancer: efficacy, safety and biomarker analysis from the SWH-B006 (neoALTALL) trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-10-01.
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Kim, Beom-Jun, Ze-Yi Zheng, Jonathan Lei, Matthew Holt, Anran Chen, Jianheng Peng, Diana Fandino, et al. "Abstract PO2-14-11: Proteogenomic approaches for the identification of NF1/neurofibromin-depleted estrogen receptor positive breast cancers for targeted treatment." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO2–14–11—PO2–14–11. http://dx.doi.org/10.1158/1538-7445.sabcs23-po2-14-11.
Повний текст джерелаАнотація:
Abstract NF1 is a key tumor suppressor that represses both RAS and estrogen receptor-α (ER) signaling in breast cancer. Blocking both pathways by fulvestrant (F), a selective ER degrader (SERD), together with binimetinib (B), a MEK inhibitor, promotes tumor regression in NF1-depleted ER+ models. We aimed to establish approaches to determine how NF1 protein levels impact B+F treatment response to improve our ability to identify B+F sensitive tumors. We examined a panel of ER+ PDX models by DNA and mRNA sequencing and found that more than half of these models carried an NF1 shallow deletion and generally have low mRNA levels. Consistent with RAS and ER activation, RET and MEK levels in NF1-depleted tumors were elevated when profiled by mass spectrometry (MS) after kinase inhibitor bead pull-down. MS showed that NF1 can also directly and selectively bind to palbociclib-conjugated beads, aiding quantification. An immunohistochemistry (IHC) assay was also established to measure NF1, but the MS-based approach was more quantitative. Combined IHC and MS analysis defined a threshold of NF1 protein loss in ER+ breast PDX, below which tumors regressed upon treatment with B+F. These results suggest that we now have a MS-verified NF1 IHC assay that can be used for patient selection as a complement to somatic genomic analysis. Citation Format: Beom-Jun Kim, Ze-Yi Zheng, Jonathan Lei, Matthew Holt, Anran Chen, Jianheng Peng, Diana Fandino, Purba Singh, Hilda Kennedy, Yongchao Dou, M Rosario Chica-Parrado, Emmanuel Bikorimana, Dan Ye, Yunguan Wang, Ariella Hanker, Nada Mohamed, Susan Hilsenbeck, Bora Lim, Jaya Ruth Asirvatham, Arun Sreekumar, Bing Zhang, George Miles, Meenakshi Anurag, Matthew Ellis, Eric Chang. Proteogenomic approaches for the identification of NF1/neurofibromin-depleted estrogen receptor positive breast cancers for targeted treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-14-11.
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Li, Yu-Wei, Ding Ma, Xiang-Rong Wu, Lei-Jie Dai, Shen Zhao, Yu-Zheng Xu, Xi Jin, et al. "Abstract PS09-09: Multiomics profiling and molecular classification refine precision treatment strategies for HER2-positive breast cancer." Cancer Research 84, no. 9_Supplement (May 2, 2024): PS09–09—PS09–09. http://dx.doi.org/10.1158/1538-7445.sabcs23-ps09-09.
Повний текст джерелаАнотація:
Abstract Background: Anti-HER2 targeted therapy has achieved a series of breakthroughs. However, the current treatment strategy regarding HER2-positive breast cancer remains indiscriminate and lacks specificity, which limits the further improvement of overall treatment response and may lead to overtreatment and extra cost for some patients. Our study aims to reveal the molecular heterogeneity of HER2-positive breast cancer to guide a more precise treatment. Patients and methods: We selected HER2-positive breast cancer patients treated at Fudan University Shanghai Cancer Center between 2013 and 2014 and conducted genomic, transcriptomic, proteomic and metabolomic profiling. We then applied a non-negative matrix factorization algorithm on transcriptomic data to obtain an unsupervised classification. And we further studied the correlation between subtypes and corresponding treatment strategies in multiple cohorts of adjuvant and neoadjuvant therapy. For clinical accessibility, we developed convolutional neural network models through deep learning algorithm based on digital pathology to identify different subtypes. Additionally, we explored novel treatment strategies using the patient-derived organoids (PDOs) models. Results: We established a novel multiomics cohort of 180 HER2- breast cancer patients and classified them into four clinically significant molecular subtypes: (1) A classical HER2-enriched (HER2-CLA, N=51) subtype characterized by strong ERBB2 signaling and remarkable sensitivity to anti-HER2-targeted therapy (pathologic complete response with dual-targeted therapy: 93%). (2) an immunomodulatory (HER2-IM, N=36) subtype characterized by an immune-activated microenvironment and excellent prognosis with current treatment (no relapse in 97% of patients with a median follow-up of 86 months). Tumors of this subtype were therefore candidates for de-escalatory treatment. (3) A luminal-like (HER2-LUM, N=55) subtype distinguished by activated estrogen receptor signaling and (4) a basal/mesenchymal-like (HER2-BM, N=38) subtype enriched in activated receptor tyrosine kinase pathways. HER2-LUM and HER2- BM showed limited benefit from anti-HER2 therapy, and thus, add-on therapies might be needed. The overall area under the curve (AUC) of the convolutional neural network model based on digital pathology for identifying different subtypes is 0.77. In the exploration of novel treatment strategies, we found in the PDO model that the HER2-LUM subtype is more sensitive to a treatment regimen combining standard (chemotherapy and targeted therapy) with subsequent endocrine therapy and CDK4/6 inhibitors compared to other subtypes. Additionally, the HER2-BM subtype demonstrated greater sensitivity to treatment with a combination of EGFR inhibitors, PDGFR inhibitors or VEGFR inhibitors. Conclusion: We uncovered a high degree of molecular heterogeneity in HER2-positive breast cancer and illustrated its impact on treatment response. More precise treatment can be given according to the characteristics of different subtypes, which may achieve good efficacy and simultaneously reduce overtreatment and extra cost. The comprehensive profiling of HER2-positive breast cancers could also serve as an important resource for further exploration. Key Words: HER2-positive breast cancer cohort; molecular classification; targeted therapy; precision treatment; de-escalatory treatment. Citation Format: Yu-Wei Li, Ding Ma, Xiang-Rong Wu, Lei-Jie Dai, Shen Zhao, Yu-Zheng Xu, Xi Jin, Xiao Yi, Ying Wang, Cai-Jin Lin, Yi-Fan Zhou, Tong Fu, Wen-Tao Yang, Ming Li, Hong Lv, Yi-Zhou Jiang, Zhi-Ming Shao. Multiomics profiling and molecular classification refine precision treatment strategies for HER2-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS09-09.
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Xie, Hui, Wei Li, Yufeng Yao, Sujie Ni, Tongbo Yi, Jinling Cheng, Qi Fang, et al. "Abstract P2-13-41: First-line pyrotinib plus trastuzumab and nab-paclitaxel for patients with HER2-positive advanced breast cancer." Cancer Research 82, no. 4_Supplement (February 15, 2022): P2–13–41—P2–13–41. http://dx.doi.org/10.1158/1538-7445.sabcs21-p2-13-41.
Повний текст джерелаАнотація:
Abstract Background: Overexpression of human epidermal factor receptor 2 (HER2) is seen in 15-20% of breast cancer and results in more aggressive clinical behavior and poor prognosis. This study (ChiCTR2000030618) analyzed the efficacy and safety of pyrotinib plus trastuzumab and nab-paclitaxel in patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer.Methods: Patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer received pyrotinib (400 mg, qd), trastuzumab (H, 8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) and nab-paclitaxel (260 mg/m² every 3 weeks) until disease progression or an unacceptable adverse event (AE). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and AEs.Results: A total of 28 patients (median age: 55.5 years [28-78]) were enrolled from April 2020 to June 2021. All 28 patients (100%) had Eastern Cooperative Oncology Group performance status of 1. The metastatic sites were in brain (14.29%), liver (25.00%), bone (28.57%) and lung (53.57%). HR+ and HR- for primary tumor accounted for 57.14% and 42.86%, respectively. Trastuzumab was previously administered in the (neo)adjuvant setting to 17(60.71%) patients. Eight patients with measurable lesions were evaluable for response. 5 (62.50%) patients had partial response (PR) and 3 (37.50%) patients achieved stable disease (SD), resulting in an ORR of 62.50% and DCR of 100.00%. Median PFS has not yet been reached. Twenty-one patients were included in the safety assessments. The most common AE was diarrhea (85.71%), but only 3 (14.29%) patients reported Grade ≥ 3 diarrhea which could be well controlled. The median onset of diarrhea was 1.5 days after start of treatment and the median duration was 9 days. Most diarrhea events were reported during the first cycle of treatment and the frequency persistently declined in the following cycles. Moreover, the AEs of all grades that were documented in ≥20% of patients included leukopenia (28.57%), anemia (23.81%), thrombocytopenia (19.05%), γ-glutamyltransferase increased (19.05%), vomiting (19.05%), rash (19.05%) and alanine aminotransferase increased (19.05%). No treatment-related deaths were reported.Conclusion: Pyrotinib plus trastuzumab and nab-paclitaxel showed promising efficacy in first-line HER2-positive breast cancer and were well tolerated. More data would be analyzed and reported in the future. Citation Format: Hui Xie, Wei Li, Yufeng Yao, Sujie Ni, Tongbo Yi, Jinling Cheng, Qi Fang, Lei Zhang, Jun Zhou, Xiaohong Wu, Chunbin Wang, Yanan Zhang, Jianwei Qin, Qing Shao, Tao Zhao, Xiaohong Huang, Lingyun Xu. First-line pyrotinib plus trastuzumab and nab-paclitaxel for patients with HER2-positive advanced breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-41.
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Shi, Qiyun, Juncheng Xuhong, Jia Ge, Feng Liu, Yang Lan, Yi Zhang, Luo Tao, Xiuwu BIan, Xiaowei Qi, and Jun Jiang. "Abstract P5-13-31: Pik3ca mutations and myc amplification are associated with pathological complete response in human epidermal growth factor receptor 2-positive breast cancer patients receiving pyrotinib combined with trastuzumab neoadjuvant treatment." Cancer Research 82, no. 4_Supplement (February 15, 2022): P5–13–31—P5–13–31. http://dx.doi.org/10.1158/1538-7445.sabcs21-p5-13-31.
Повний текст джерелаАнотація:
Abstract Background: Our previous study reported a good efficacy and safety of pyrotinib combined with trastuzumab neoadjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. We further explored the potential biomarkers for the efficacy of pyrotinib combined with trastuzumab neoadjuvant treatment in HER2-positive breast cancer patients. Methods:To date, a total of 162 patients with early-stage breast cancer were enrolled for the neoadjuvant pyrotinib combined with trastuzumab treatment clinical trial (ChiCTR1900022293). By the method of 425 genes next-generation sequencing (NGS), the genomic characteristics of them were evaluated for the potential correlation with postoperative pathological complete response (pCR). Results:. Among the cohort of 162 cases, a total of 43 patients have completed the whole therapy as well as final surgery and acquired qualified sequencing analysis report, and 25 of them achieved total pCR. The most frequently mutated driver genes were TP53 (80%), PIK3CA (46%), ERBB2 (10%), NF1 (8%), NBN (8%), ATRX (8%), respectively. In terms of somatic copy number alterations, the most frequent alterations are gain or amplification of ERBB2 (66%), MYC (24%), CKD12 (14%), CCND1 (12%) and ZNF217 (12%), respectively. The median tumor mutation burden (TMB) was 4.76 mut/Mb (0.00-29.61). Compared with pCR populations, non-pCR populations had higher median TMB but not statistically significant (5.29 vs 3.85 mut/Mb, P=0.141). In addition, the pCR rate of patients with wild-type PIK3CA is significantly higher than that of patients with mutated PIK3CA (80.0% vs 27.8%, P = 0.001), and those with amplified MYC are more likely to achieve pCR (22.2% vs 67.6%, P = 0.023). Conclusions:Preliminary results suggested that HER2-positive breast cancer patients with activating mutations in PIK3CA and amplified MYC are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy, which need larger sample size to validate. Citation Format: Qiyun Shi, Juncheng Xuhong, Jia Ge, Feng Liu, Yang Lan, Yi Zhang, Luo Tao, Xiuwu BIan, Xiaowei Qi, Jun Jiang. Pik3ca mutations and myc amplification are associated with pathological complete response in human epidermal growth factor receptor 2-positive breast cancer patients receiving pyrotinib combined with trastuzumab neoadjuvant treatment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-31.
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Shi, Qiyun, Juncheng Xuhong, Hao Tian, Yi Zhang, Jun Jiang, and Xiaowei Qi. "Abstract P5-02-52: Predictive and prognosis value of PIK3CA mutations in HER2-positive breast cancer treated with tyrosine kinase inhibitors (TKIs): a systemic review and meta-analysis." Cancer Research 83, no. 5_Supplement (March 1, 2023): P5–02–52—P5–02–52. http://dx.doi.org/10.1158/1538-7445.sabcs22-p5-02-52.
Повний текст джерелаАнотація:
Abstract Background: PIK3CA mutations is one of the most frequent gene alterations in breast cancers, which was reported to be related to the treatment response of anti-HER2 regimens. However, the relationship between PIK3CA mutations and treatment response of a tyrosine kinase inhibitors (TKIs) is still unclear. We thus conducted a systemic review and meta-analysis to investigate the predictive and prognosis value of PIK3CA mutations in HER2-positive breast cancer treated with TKIs. Methods: The following databases were searched from inception to July 2022: Medline, Embase and the Cochrane Library. Abstracts from conferences were also reviewed for inclusion. The critical information was extracted from eligible studies. Results: A total of 16 reports including 17 studies were assessed for eligibility, enrolling 1706 patients. Ten studies including 902 patients were in the neoadjuvant setting, the pCR rate is significantly higher in PIK3CA wild-type (WT) patients than in mutated-type (MT) patients (OR = 0.45; 95% CI: 0.31-0.65; P< 0.001). Seven studies including 804 patients were in the metastatic setting, the pooled objective response rate (ORR) is significantly higher in PIK3CA WT patients than in MT patients (OR = 0.40; 95% CI: 0.23-0.70; P = 0.001), and similarly, the clinical benefit rate (CBR) in WT patients is also higher (OR = 0.43; 95% CI: 0.19-0.98; P=0.045). A total of 4 metastasis studies reported progression free survival (PFS), and 2 of them reported overall survival (OS), revealing a marginally significant relationship between PIK3CA mutation and worse PFS (HR = 0.82; 95% CI: 0.67-1.00; P=0.052) and OS (HR=0.63, 95%CI:0.39-1.02; P=0.062). No evidence of publication bias was found in both the neoadjuvant setting and metastatic setting. Conclusion: Our findings indicate that PIK3CA mutations is significantly associated with a lower rate of pCR when treated with TKI-containing regimens in neoadjuvant chemotherapy of early-stage HER2-positive breast cancer, and is significantly associated with lower ORR and CBR in metastatic HER2-positive breast cancer. Citation Format: Qiyun Shi, Juncheng Xuhong, Hao Tian, Yi Zhang, Jun Jiang, Xiaowei Qi. Predictive and prognosis value of PIK3CA mutations in HER2-positive breast cancer treated with tyrosine kinase inhibitors (TKIs): a systemic review and meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-52.
Книги з теми "San jun yi zhang dui"
1
Si da ye zhan jun zhang zhan ji shi: Zhongguo ren min jie fang jun di yi, di er, di san, di si ye zhan jun zheng zhan feng yun quan ji lu. Beijing: Zhong yang bian yi chu ban she, 2004.
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2
Qi san yi bu dui xi jun zhan yi hai yan jiu: Yi Ha'erbin shu yi liu xing wei li. Ha'erbin Shi: Heilongjiang ren min chu ban she, 2009.
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3
1956-, Wallace David, and Wu Tianwei, eds. Qi san yi bu dui: Di er ci shi jie da zhan zhong de Riben xi jun zhan. Taibei Xian Xindian Shi: Guo shi guan bian yin, 1992.
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4
1956-, Wallace David, and Wu Tianwei, eds. Qi san yi bu dui: Di er ci shi jie da zhan zhong di Riben xi jun zhan. Taibei Xian Xindian Shi: Guo shi guan bian yin, 1992.
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5
Zhu, Donald Knox, Liang Qing Yi, and Xia Jinbiao Yi, eds. San jiao zhou de jue qi: Mei jun san jiao zhou te zhong zuo zhan bu dui chuang shi ren hui yi lu = Delta force. Beijing: Hua xue gong ye chu ban she, 2015.
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6
Ou, Xiangjing. Yi dai yi lu, xi bu jue qi: "Shi san wu" shi qi Zhenning Buyizu Miaozu Zizhixian rong ru "yi dai yi lu" zhan lüe yan jiu. Chengdu: Xi nan jiao tong da xue chu ban she, 2016.
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7
Guang zhou jun qu zheng zhi bu zu zhi bu. Yi xin qun: Mo fan shi jian"san ge dai biao"de xian jin zhan shi. Guang zhou: Nan fang ri bao chu ban she, 2001.
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Zhong gong zhong yang xuan chuan bu. Xi jin ping xin shi dai zhong guo te se she hui zhu yi si xiang san shi jiang. Beijing: Xue xi chu ban she, 2018.
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Yi ci cheng gong de deng lu zhan: Zhui yi Zhang Aiping jiang jun zhi hui shou ci lu hai kong san jun lian he du hai qiang gong Yijiangshan Dao. Beijing Shi: Hai chao she ying chu ban she, 2006.
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Jun dui yi liao bao zhang zhi du gai ge yu wei sheng gong zuo gui fan hua guan li shi yong shou ce. [Beijing Shi]: Yin sheng yin xiang chu ban she, 2004.
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