NPJ Breast Cancer最新文献_第9页

The survival benefit of adjuvant trastuzumab with or without chemotherapy in the management of small (T1mic, T1a, T1b, T1c), node negative HER2+ breast cancer. 曲妥珠单抗辅助化疗或不辅助化疗在治疗小型（T1mic、T1a、T1b、T1c）、结节阴性 HER2+ 乳腺癌中的生存获益。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2024-06-19 DOI: 10.1038/s41523-024-00652-4

Kai C C Johnson, Ai Ni, Dionisia Quiroga, Ashley C Pariser, Preeti K Sudheendra, Nicole O Williams, Sagar D Sardesai, Mathew Cherian, Daniel G Stover, Margaret Gatti-Mays, Bhuvaneswari Ramaswamy, Maryam Lustberg, Sachin Jhawar, Roman Skoracki, Robert Wesolowski

{"title":"The survival benefit of adjuvant trastuzumab with or without chemotherapy in the management of small (T1mic, T1a, T1b, T1c), node negative HER2+ breast cancer.","authors":"Kai C C Johnson, Ai Ni, Dionisia Quiroga, Ashley C Pariser, Preeti K Sudheendra, Nicole O Williams, Sagar D Sardesai, Mathew Cherian, Daniel G Stover, Margaret Gatti-Mays, Bhuvaneswari Ramaswamy, Maryam Lustberg, Sachin Jhawar, Roman Skoracki, Robert Wesolowski","doi":"10.1038/s41523-024-00652-4","DOIUrl":"10.1038/s41523-024-00652-4","url":null,"abstract":"There is limited data regarding the added benefit of adjuvant systemic therapy in the management of small, node-negative, HER2+ breast cancer. In a multi-institutional retrospective analysis using the American Society of Clinical Oncology CancerLinQ database, we compared survival outcomes among T1a-c N0 HER2+ patients diagnosed between 2010 to 2021 who received locoregional therapy alone or in combination with adjuvant trastuzumab (+/- chemotherapy). Primary outcomes were invasive disease-free survival (iDFS) and overall survival (OS). Of the 1,184 patients, 436 received locoregional therapy alone. We found a statistically significant improvement in iDFS (HR 0.73, P = 0.003) and OS (HR 0.63, P = 0.023) on univariate analysis with adjuvant trastuzumab with or without chemotherapy which remained statistically significant on multivariate analysis. Three-arm univariate analysis found that iDFS was significantly improved with trastuzumab monotherapy (P = 0.003) and combination therapy (P = 0.027) compared to observation. Subgroup data suggests that T1b/c tumors derive the greatest benefit.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"49"},"PeriodicalIF":6.5,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and validation of a clinical breast cancer tool for accurate prediction of recurrence. 开发并验证用于准确预测复发的临床乳腺癌工具。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2024-06-15 DOI: 10.1038/s41523-024-00651-5

Asim Dhungana, Augustin Vannier, Fangyuan Zhao, Jincong Q Freeman, Poornima Saha, Megan Sullivan, Katharine Yao, Elbio M Flores, Olufunmilayo I Olopade, Alexander T Pearson, Dezheng Huo, Frederick M Howard

{"title":"Development and validation of a clinical breast cancer tool for accurate prediction of recurrence.","authors":"Asim Dhungana, Augustin Vannier, Fangyuan Zhao, Jincong Q Freeman, Poornima Saha, Megan Sullivan, Katharine Yao, Elbio M Flores, Olufunmilayo I Olopade, Alexander T Pearson, Dezheng Huo, Frederick M Howard","doi":"10.1038/s41523-024-00651-5","DOIUrl":"10.1038/s41523-024-00651-5","url":null,"abstract":"Given high costs of Oncotype DX (ODX) testing, widely used in recurrence risk assessment for early-stage breast cancer, studies have predicted ODX using quantitative clinicopathologic variables. However, such models have incorporated only small cohorts. Using a cohort of patients from the National Cancer Database (NCDB, n = 53,346), we trained machine learning models to predict low-risk (0-25) or high-risk (26-100) ODX using quantitative estrogen receptor (ER)/progesterone receptor (PR)/Ki-67 status, quantitative ER/PR status alone, and no quantitative features. Models were externally validated on a diverse cohort of 970 patients (median follow-up 55 months) for accuracy in ODX prediction and recurrence. Comparing the area under the receiver operating characteristic curve (AUROC) in a held-out set from NCDB, models incorporating quantitative ER/PR (AUROC 0.78, 95% CI 0.77-0.80) and ER/PR/Ki-67 (AUROC 0.81, 95% CI 0.80-0.83) outperformed the non-quantitative model (AUROC 0.70, 95% CI 0.68-0.72). These results were preserved in the validation cohort, where the ER/PR/Ki-67 model (AUROC 0.87, 95% CI 0.81-0.93, p = 0.009) and the ER/PR model (AUROC 0.86, 95% CI 0.80-0.92, p = 0.031) significantly outperformed the non-quantitative model (AUROC 0.80, 95% CI 0.73-0.87). Using a high-sensitivity rule-out threshold, the non-quantitative, quantitative ER/PR and ER/PR/Ki-67 models identified 35%, 30% and 43% of patients as low-risk in the validation cohort. Of these low-risk patients, fewer than 3% had a recurrence at 5 years. These models may help identify patients who can forgo genomic testing and initiate endocrine therapy alone. An online calculator is provided for further study.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"46"},"PeriodicalIF":6.5,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pyrotinib and trastuzumab plus palbociclib and fulvestrant in HR+/HER2+ breast cancer patients with brain metastasis. 派罗替尼和曲妥珠单抗联合帕博西尼和氟维司群治疗脑转移的 HR+/HER2+ 乳腺癌患者。

IF 5.9 2区医学

NPJ Breast Cancer Pub Date : 2024-06-13 DOI: 10.1038/s41523-024-00646-2

Dongshao Chen, Fei Xu, Yongkui Lu, Wen Xia, Caiwen Du, Dun Xiong, Dong Song, Yanxia Shi, Zhongyu Yuan, Qiufan Zheng, Kuikui Jiang, Xin An, Cong Xue, Jiajia Huang, Xiwen Bi, Meiting Chen, Jingmin Zhang, Shusen Wang, Ruoxi Hong

{"title":"Pyrotinib and trastuzumab plus palbociclib and fulvestrant in HR+/HER2+ breast cancer patients with brain metastasis.","authors":"Dongshao Chen, Fei Xu, Yongkui Lu, Wen Xia, Caiwen Du, Dun Xiong, Dong Song, Yanxia Shi, Zhongyu Yuan, Qiufan Zheng, Kuikui Jiang, Xin An, Cong Xue, Jiajia Huang, Xiwen Bi, Meiting Chen, Jingmin Zhang, Shusen Wang, Ruoxi Hong","doi":"10.1038/s41523-024-00646-2","DOIUrl":"10.1038/s41523-024-00646-2","url":null,"abstract":"Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients are at a high risk of developing metastases in the brain. However, research focusing on treatment strategies for hormonal receptor positive (HR+), HER2+ BC patients with brain metastases (BM) remains limited. Thus, a multi-center, prospective trial was conducted in China. Women over the age of 18 who were naive to whole brain radiotherapy and had estrogen receptor (ER)/progesterone-receptor (PgR) positive, HER2+ BM were treated with palbociclib, fulvestrant, trastuzumab and pyrotinib, until disease progression or the development of intolerable side effects. The primary endpoint was objective response rate (ORR) in the central nervous system (CNS). This ongoing study is still recruiting participants and is registered with ClinicalTrials.gov (NCT04334330). This report presents the findings from an interim analysis. From December 4, 2020, to November 2, 2022, 15 patients were enrolled. Among the 14 patients who were evaluable for clinical response, the ORR was 35.7% (95% CI: 12.8-64.9%), with a CNS-ORR of 28.6% (95% CI: 8.4-58.1%). The median follow-up period was 6.3 months (range, 2.1-14.3 months), during which the median progression-free survival (PFS) was 10.6 months (95% CI: 4.3-16.9 months), and the median time to CNS progression was 8.5 months (95% CI: 5.9-11.1 months). The most common adverse event was diarrhea (93%), with 33% having grade 3 and 6.7% having grade 4. The study suggests that the combination of palbociclib, trastuzumab, pyrotinib and fulvestrant offers a promising chemo-free treatment strategy for HR+, HER2+ BC patients with BM.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"45"},"PeriodicalIF":5.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Allostatic load as a predictor of postoperative complications in patients with breast cancer. 预测乳腺癌患者术后并发症的代谢负荷。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2024-06-12 DOI: 10.1038/s41523-024-00654-2

J C Chen, Mohamed I Elsaid, Demond Handley, Lisa Anderson, Barbara L Andersen, William E Carson, Joal D Beane, Alex Kim, Roman Skoracki, Timothy M Pawlik, Samilia Obeng-Gyasi

{"title":"Allostatic load as a predictor of postoperative complications in patients with breast cancer.","authors":"J C Chen, Mohamed I Elsaid, Demond Handley, Lisa Anderson, Barbara L Andersen, William E Carson, Joal D Beane, Alex Kim, Roman Skoracki, Timothy M Pawlik, Samilia Obeng-Gyasi","doi":"10.1038/s41523-024-00654-2","DOIUrl":"10.1038/s41523-024-00654-2","url":null,"abstract":"Allostatic load (AL) is a biological measure of cumulative exposure to socioenvironmental stressors (e.g., poverty). This study aims to examine the association between allostatic load (AL) and postoperative complications (POC) among patients with breast cancer. Females ages 18+ with stage I-III breast cancer who received surgical management between 01/01/2012-12/31/2020 were identified in the Ohio State Cancer registry. The composite AL measure included biomarkers from the cardiovascular, metabolic, immune, and renal systems. High AL was defined as composite scores greater than the cohort's median (2.0). POC within 30 days of surgery were examined. Univariable and multivariable regression analysis examined the association between AL and POC. Among 4459 patients, 8.2% had POC. A higher percentage of patients with POC were unpartnered (POC 44.7% vs no POC 35.5%), government-insured (POC 48.2% vs no POC 38.3%) and had multiple comorbidities (POC 32% vs no POC 20%). Patients who developed POC were more likely to have undergone sentinel lymph node biopsy followed by axillary lymph node dissection (POC 51.2% vs no POC 44.6%). High AL was associated with 29% higher odds of POC (aOR 1.29, 95% CI 1.01-1.63). A one-point increase in AL was associated with 8% higher odds of POC (aOR 1.08, 95% CI 1.02-1.16) and a quartile increase in AL was associated with 13% increased odds of POC (aOR 1.13, 95% CI 1.01-1.26). Among patients undergoing breast cancer surgery, increased exposure to adverse socioenvironmental stressors, operationalized as AL, was associated with higher odds of postoperative complications.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"44"},"PeriodicalIF":6.5,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion. 在 TNBC 脑转移瘤临床前模型中靶向脂肪酸合成酶与 SN-38 协同作用，并能抑制侵袭。

IF 5.9 2区医学

NPJ Breast Cancer Pub Date : 2024-06-10 DOI: 10.1038/s41523-024-00656-0

Habib A Serhan, Liwei Bao, Xu Cheng, Zhaoping Qin, Chia-Jen Liu, Jason A Heth, Aaron M Udager, Matthew B Soellner, Sofia D Merajver, Aki Morikawa, Nathan M Merrill

引用次数: 0

Pure estrogen receptor antagonists potentiate capecitabine activity in ESR1-mutant breast cancer. 纯雌激素受体拮抗剂可增强卡培他滨在 ESR1 突变乳腺癌中的活性。

IF 5.9 2区医学

NPJ Breast Cancer Pub Date : 2024-06-08 DOI: 10.1038/s41523-024-00647-1

Albert Grinshpun, Douglas Russo, Wen Ma, Ana Verma, Francisco Hermida-Prado, Shira Sherman, Giorgio Gaglia, Sheheryar Kabraji, Gregory Kirkner, Melissa E Hughes, Nancy U Lin, Zachary Sandusky, Agostina Nardone, Cristina Guarducci, Quang-De Nguyen, Sandro Santagata, Zsuzsanna Nagy, Rinath Jeselsohn

{"title":"Pure estrogen receptor antagonists potentiate capecitabine activity in ESR1-mutant breast cancer.","authors":"Albert Grinshpun, Douglas Russo, Wen Ma, Ana Verma, Francisco Hermida-Prado, Shira Sherman, Giorgio Gaglia, Sheheryar Kabraji, Gregory Kirkner, Melissa E Hughes, Nancy U Lin, Zachary Sandusky, Agostina Nardone, Cristina Guarducci, Quang-De Nguyen, Sandro Santagata, Zsuzsanna Nagy, Rinath Jeselsohn","doi":"10.1038/s41523-024-00647-1","DOIUrl":"10.1038/s41523-024-00647-1","url":null,"abstract":"The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient-derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"42"},"PeriodicalIF":5.9,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. 作者更正：萨希珠单抗戈维替康治疗转移性三阴性乳腺癌的 ASCENT 3 期试验的安全性分析。

IF 5.9 2区医学

NPJ Breast Cancer Pub Date : 2024-06-06 DOI: 10.1038/s41523-024-00650-6

Hope S Rugo, Sara M Tolaney, Delphine Loirat, Kevin Punie, Aditya Bardia, Sara A Hurvitz, Joyce O'Shaughnessy, Javier Cortés, Véronique Diéras, Lisa A Carey, Luca Gianni, Martine J Piccart, Sibylle Loibl, David M Goldenberg, Quan Hong, Martin Olivo, Loretta M Itri, Kevin Kalinsky

引用次数: 0

Gedatolisib shows superior potency and efficacy versus single-node PI3K/AKT/mTOR inhibitors in breast cancer models. Gedatolisib 在乳腺癌模型中显示出优于单节点 PI3K/AKT/mTOR 抑制剂的效力和疗效。

IF 5.9 2区医学

NPJ Breast Cancer Pub Date : 2024-06-05 DOI: 10.1038/s41523-024-00648-0

Stefano Rossetti, Aaron Broege, Adrish Sen, Salmaan Khan, Ian MacNeil, Jhomary Molden, Ross Kopher, Stephen Schulz, Lance Laing

{"title":"Gedatolisib shows superior potency and efficacy versus single-node PI3K/AKT/mTOR inhibitors in breast cancer models.","authors":"Stefano Rossetti, Aaron Broege, Adrish Sen, Salmaan Khan, Ian MacNeil, Jhomary Molden, Ross Kopher, Stephen Schulz, Lance Laing","doi":"10.1038/s41523-024-00648-0","DOIUrl":"10.1038/s41523-024-00648-0","url":null,"abstract":"The PI3K, AKT, and mTOR (PAM) pathway is frequently dysregulated in breast cancer (BC) to accommodate high catabolic and anabolic activities driving tumor growth. Current therapeutic options for patients with hormone receptor (HR) + / HER2- advanced BC (ABC) include PAM inhibitors that selectively inhibit only one PAM pathway node, which can lead to drug resistance as cells rapidly adapt to maintain viability. We hypothesized that gedatolisib, which potently inhibits all Class I PI3K isoforms, as well as mTORC1 and mTORC2, may be more effective in BC cells than single-node PAM inhibitors by limiting adaptive resistances. By using multiple functional assays, a panel of BC cell lines was evaluated for their sensitivity to four different PAM inhibitors: gedatolisib (pan-PI3K/mTOR inhibitor), alpelisib (PI3Kα inhibitor), capivasertib (AKT inhibitor), and everolimus (mTORC1 inhibitor). Gedatolisib exhibited more potent and efficacious anti-proliferative and cytotoxic effects regardless of the PAM pathway mutational status of the cell lines compared to the single-node PAM inhibitors. The higher efficacy of gedatolisib was confirmed in three-dimensional culture and in BC PDX models. Mechanistically, gedatolisib decreased cell survival, DNA replication, cell migration and invasion, protein synthesis, glucose consumption, lactate production, and oxygen consumption more effectively than the other PAM inhibitors tested. These results indicate that inhibition of multiple PAM pathway nodes by a pan-PI3K/mTOR inhibitor like gedatolisib may be more effective at inducing anti-tumor activity than single-node PAM inhibitors. A global Phase 3 study is currently evaluating gedatolisib plus fulvestrant with and without palbociclib in patients with HR+/HER2- ABC.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"40"},"PeriodicalIF":5.9,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11153628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dose dense doxorubicin plus cyclophosphamide in a modified KEYNOTE522 regimen for triple negative breast cancer. 在治疗三阴性乳腺癌的 KEYNOTE522 改良方案中采用剂量密集的多柔比星加环磷酰胺。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2024-06-04 DOI: 10.1038/s41523-024-00643-5

Nicholas Mai, Sara Myers, Sherry Shen, Stephanie Downs-Canner, Mark Robson, Larry Norton, Yuan Chen, Tiffany Traina, Nour Abuhadra

{"title":"Dose dense doxorubicin plus cyclophosphamide in a modified KEYNOTE522 regimen for triple negative breast cancer.","authors":"Nicholas Mai, Sara Myers, Sherry Shen, Stephanie Downs-Canner, Mark Robson, Larry Norton, Yuan Chen, Tiffany Traina, Nour Abuhadra","doi":"10.1038/s41523-024-00643-5","DOIUrl":"10.1038/s41523-024-00643-5","url":null,"abstract":"The KEYNOTE-522 (KN522) regimen for neoadjuvant treatment of triple negative breast cancer (TNBC) utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has demonstrated superior overall survival (OS) compared to q3week AC in anthracycline and taxane-based regimens. We performed a retrospective analysis assessing the use of ddAC in KN522 and the impact of sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab on multiple outcomes. 128 patients with TNBC were included. Overall pathologic complete response (pCR) rate of 56%. Sequencing of ddAC vs CbT first showed no difference in pCR rate (ddAC 55% vs. CbT 58%, p = 0.77). However, ddAC first compared to CbT first correlated with a significant increase in the incidence of overall treatment delays (ddAC 70% vs. CbT 51%, p = 0.03), with cytopenias most frequent (ddAC 59% vs. CbT 31%, p = 0.001). ddAC in a modified KN522 regimen is safe, tolerable, and effective. Efficacy is comparable regardless of chemotherapy sequencing, but ddAC first is significantly associated with higher rates of treatment delays and cytopenias.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"39"},"PeriodicalIF":6.5,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11150442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overexpression of COL11A1 confers tamoxifen resistance in breast cancer. COL11A1 的过表达会导致乳腺癌患者对他莫昔芬产生抗药性。

IF 5.9 2区医学

NPJ Breast Cancer Pub Date : 2024-05-28 DOI: 10.1038/s41523-024-00645-3

Chengxiao Fu, Shan Duan, Xiaoming Zhou, Yingcai Meng, Xisha Chen

{"title":"Overexpression of COL11A1 confers tamoxifen resistance in breast cancer.","authors":"Chengxiao Fu, Shan Duan, Xiaoming Zhou, Yingcai Meng, Xisha Chen","doi":"10.1038/s41523-024-00645-3","DOIUrl":"10.1038/s41523-024-00645-3","url":null,"abstract":"Breast cancer is the most commonly diagnosed malignancy and benefits from endocrine agents such as tamoxifen. However, the development of drug resistance in cancerous cells often leads to recurrence, thus limiting the therapeutic benefit. Identification of potential biomarkers that can predict response to tamoxifen and recognize patients who will clinically benefit from this therapy is urgently needed. In this study, we report that high collagen type XI alpha 1 (COL11A1) expression was associated with poor therapeutic response and prognosis in breast cancer patients treated with tamoxifen. To confirm the role of COL11A1 in the development of tamoxifen resistance, we established MCF-7/COL11A1 and T47D/COL11A1 cell lines, which stably expressed COL11A1. Compared with parental MCF-7 and T47D, MCF-7/COL11A1 and T47D/COL11A1 cells were more resistant to 4-OHT-induced growth inhibition. Moreover, the level of COL11A1 expression was upregulated in tamoxifen-resistant MCF-7/TamR and T47D/TamR cell lines, and depletion of COL11A1 markedly sensitized the cells to 4-OHT in vitro and in vivo. Interestingly, the level of estrogen receptor α (ERα) expression was elevated, probably due to the increased COL11A1 in TamR cells. In addition, knockdown of COL11A1 decreased the expression of ERα and its downstream target genes. Overall, our findings suggest that overexpressed COL11A1 contributes to tamoxifen resistance, and targeting COL11A1 holds great promise for reversing endocrine resistance.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"38"},"PeriodicalIF":5.9,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0