The Cry1Ac protoxin from Bacillus thuringiensis is a systemic and mucosal adjuvant, able to confer protective immunity in different infection murine models and induce both Th1 and TCD8+ cytotoxic lymphocyte responses, which are required to induce antitumor immunity. The Cry1Ac toxin, despite having not being characterized as an adjuvant, has also proved to be immunogenic and able to activate macrophages. Here, we investigated the potential antitumor adjuvant effect conferred by the Cry1Ac protoxin and Cry1Ac toxin in a triple negative breast cancer (TNBC) murine model. First, we evaluated the ability of Cry1Ac proteins to improve dendritic cell (DC) activation and cellular response through intraperitoneal (i.p.) coadministration with the 4T1 cellular lysate. Mice coadministered with the Cry1Ac protoxin showed an increase in the number and activation of CD11c+MHCII- and CD11c+MHCII+low in the peritoneal cavity and an increase in DC activation (CD11c+MHCII+) in the spleen. Cry1Ac protoxin increased the proliferation of TCD4+ and TCD8+ lymphocytes in the spleen and mesenteric lymph nodes (MLN), while the Cry1Ac toxin only increased the proliferation of TCD4+ and TCD8+ in the MLN. Remarkably, when tested in the in vivo TNBC mouse model, prophylactic immunizations with 4T1 lysates plus the Cry1Ac protoxin protected mice from developing tumors. The antitumor effect conferred by the Cry1Ac protoxin also increased specific cytotoxic T cell responses, and prevented the typical tumor-related decrease of T cells (TCD3+ and TCD4+) as well the increase of myeloid-derived suppressor cells (MDSC) in spleen. Also in the tumor microenvironment of mice coadministered twice with Cry1Ac protoxin immunological improvements were found such as reductions in immunosupressive populations (T regulatory lymphocytes and MDSC) along with increases in macrophages upregulating CD86. These results show a differential antitumor adjuvant capability of Cry1Ac proteins, highlighting the ability of Cry1Ac protoxin to enhance local and systemic tumor immunity in TNBC. Finally, using a therapeutic approach, we evaluated the coadministration of Cry1Ac protoxin with doxorubicin. A significant reduction in tumor volume and lung metastasis was found, with increased intratumoral levels of tumor necrosis factor-α and IL-6 with respect to the vehicle group, further supporting its antitumor applicability.
{"title":"Cry1Ac Protoxin Confers Antitumor Adjuvant Effect in a Triple-Negative Breast Cancer Mouse Model by Improving Tumor Immunity.","authors":"Roberto Raúl Servin-Garrido, Damaris Ilhuicatzi-Alvarado, Ángel de Jesús Jiménez-Chávez, Leticia Moreno-Fierros","doi":"10.1177/11782234211065154","DOIUrl":"https://doi.org/10.1177/11782234211065154","url":null,"abstract":"<p><p>The Cry1Ac protoxin from <i>Bacillus thuringiensis</i> is a systemic and mucosal adjuvant, able to confer protective immunity in different infection murine models and induce both Th1 and TCD8+ cytotoxic lymphocyte responses, which are required to induce antitumor immunity. The Cry1Ac toxin, despite having not being characterized as an adjuvant, has also proved to be immunogenic and able to activate macrophages. Here, we investigated the potential antitumor adjuvant effect conferred by the Cry1Ac protoxin and Cry1Ac toxin in a triple negative breast cancer (TNBC) murine model. First, we evaluated the ability of Cry1Ac proteins to improve dendritic cell (DC) activation and cellular response through intraperitoneal (i.p.) coadministration with the 4T1 cellular lysate. Mice coadministered with the Cry1Ac protoxin showed an increase in the number and activation of CD11c+MHCII- and CD11c+MHCII+<sup>low</sup> in the peritoneal cavity and an increase in DC activation (CD11c+MHCII+) in the spleen. Cry1Ac protoxin increased the proliferation of TCD4+ and TCD8+ lymphocytes in the spleen and mesenteric lymph nodes (MLN), while the Cry1Ac toxin only increased the proliferation of TCD4+ and TCD8+ in the MLN. Remarkably, when tested in the in vivo TNBC mouse model, prophylactic immunizations with 4T1 lysates plus the Cry1Ac protoxin protected mice from developing tumors. The antitumor effect conferred by the Cry1Ac protoxin also increased specific cytotoxic T cell responses, and prevented the typical tumor-related decrease of T cells (TCD3+ and TCD4+) as well the increase of myeloid-derived suppressor cells (MDSC) in spleen. Also in the tumor microenvironment of mice coadministered twice with Cry1Ac protoxin immunological improvements were found such as reductions in immunosupressive populations (T regulatory lymphocytes and MDSC) along with increases in macrophages upregulating CD86. These results show a differential antitumor adjuvant capability of Cry1Ac proteins, highlighting the ability of Cry1Ac protoxin to enhance local and systemic tumor immunity in TNBC. Finally, using a therapeutic approach, we evaluated the coadministration of Cry1Ac protoxin with doxorubicin. A significant reduction in tumor volume and lung metastasis was found, with increased intratumoral levels of tumor necrosis factor-α and IL-6 with respect to the vehicle group, further supporting its antitumor applicability.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"16 ","pages":"11782234211065154"},"PeriodicalIF":2.9,"publicationDate":"2022-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/81/2f/10.1177_11782234211065154.PMC8738886.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39676486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/11782234221086684
M. Davey, M. Davey, Vinitha Richard, W. Wyns, O. Soliman, N. Miller, A. Lowery, M. Kerin
Purpose: Increased appreciation of the human epidermal growth factor receptor-2 (HER2/neu) signalling pathway has led to the development of targeted therapeutic agents used in conjunction with chemotherapy to improve outcomes for HER2 overexpressing (HER2+) breast cancer. For neoadjuvant therapy, response rates can be unpredictable – novel biomarkers predicting effectiveness are required to enhance oncological outcomes for these patients, and microRNA may prove effective. Our objective was to identify microRNA (miRNA) expression patterns predictive of response to neoadjuvant chemotherapy (NAC) and/or anti-HER2 targeted therapies in patients being treated for early-stage HER2+ breast cancer. Methods: A search was performed of the PUBMED, SCOPUS, Web of Science, and EMBASE in accordance to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Results: Overall, 15 studies including 1335 patients were included. These studies highlighted an expression profile of 73 miRNA and their ability to predict tumour response to neoadjuvant therapies was correlated. Results from 11 studies were in relation to circulatory miRNA and 4 studies included data from tumour tissue. Overall, upregulation and downregulation of 41 miRNA and 29 miRNA, respectively, predicted differential response to neoadjuvant therapy. Expression levels of 3 miRNA (miR-21, miR-210, and miR-376c-3p) were inconclusive in predicting therapeutic response, while ‘aberrant’ expression of circulating miR-199a predicted pathological complete response (pCR) to NAC. Conclusions: This systematic review outlines expression patterns of a number of miRNA which correlate with response to NAC and/or anti-HER2 therapies. Future translational research evaluating predictive biomarkers of primary response to neoadjuvant therapy in HER2+ breast cancer may consider these results.
目的:人表皮生长因子受体-2 (HER2/neu)信号通路的增加导致靶向治疗药物的发展，这些药物与化疗联合使用，以改善HER2过表达(HER2+)乳腺癌的预后。对于新辅助治疗，反应率可能是不可预测的——需要新的生物标志物来预测有效性，以提高这些患者的肿瘤预后，而microRNA可能证明是有效的。我们的目的是鉴定microRNA (miRNA)表达模式，预测早期HER2+乳腺癌患者对新辅助化疗(NAC)和/或抗HER2靶向治疗的反应。方法:根据系统评价和meta分析的首选报告项目(PRISMA)指南，对PUBMED、SCOPUS、Web of Science和EMBASE进行检索。结果:共纳入15项研究，1335例患者。这些研究强调了73 miRNA的表达谱及其预测肿瘤对新辅助治疗反应的能力是相关的。11项研究的结果与循环miRNA有关，4项研究的数据来自肿瘤组织。总的来说，41 miRNA和29 miRNA的上调和下调分别预测了新辅助治疗的差异反应。3种miRNA (miR-21、miR-210和miR-376c-3p)的表达水平在预测治疗反应方面尚无定论，而循环miR-199a的“异常”表达可预测NAC的病理完全反应(pCR)。结论:本系统综述概述了与NAC和/或抗her2治疗反应相关的许多miRNA的表达模式。未来评估HER2+乳腺癌对新辅助治疗主要反应的预测性生物标志物的转化研究可能会考虑这些结果。
{"title":"Overview of MicroRNA Expression in Predicting Response to Neoadjuvant Therapies in Human Epidermal Growth Receptor-2 Enriched Breast Cancer – A Systematic Review","authors":"M. Davey, M. Davey, Vinitha Richard, W. Wyns, O. Soliman, N. Miller, A. Lowery, M. Kerin","doi":"10.1177/11782234221086684","DOIUrl":"https://doi.org/10.1177/11782234221086684","url":null,"abstract":"Purpose: Increased appreciation of the human epidermal growth factor receptor-2 (HER2/neu) signalling pathway has led to the development of targeted therapeutic agents used in conjunction with chemotherapy to improve outcomes for HER2 overexpressing (HER2+) breast cancer. For neoadjuvant therapy, response rates can be unpredictable – novel biomarkers predicting effectiveness are required to enhance oncological outcomes for these patients, and microRNA may prove effective. Our objective was to identify microRNA (miRNA) expression patterns predictive of response to neoadjuvant chemotherapy (NAC) and/or anti-HER2 targeted therapies in patients being treated for early-stage HER2+ breast cancer. Methods: A search was performed of the PUBMED, SCOPUS, Web of Science, and EMBASE in accordance to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Results: Overall, 15 studies including 1335 patients were included. These studies highlighted an expression profile of 73 miRNA and their ability to predict tumour response to neoadjuvant therapies was correlated. Results from 11 studies were in relation to circulatory miRNA and 4 studies included data from tumour tissue. Overall, upregulation and downregulation of 41 miRNA and 29 miRNA, respectively, predicted differential response to neoadjuvant therapy. Expression levels of 3 miRNA (miR-21, miR-210, and miR-376c-3p) were inconclusive in predicting therapeutic response, while ‘aberrant’ expression of circulating miR-199a predicted pathological complete response (pCR) to NAC. Conclusions: This systematic review outlines expression patterns of a number of miRNA which correlate with response to NAC and/or anti-HER2 therapies. Future translational research evaluating predictive biomarkers of primary response to neoadjuvant therapy in HER2+ breast cancer may consider these results.","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"49 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75537308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/11782234221090197
A. Mohan, Vinay Kumar, S. Brahmachari, B. Pandya
Purpose: To study the clinico-pathological profile of breast cancer patients and the prevalence of uterine fibroids in them, their hormonal levels and hormone receptor status. Patients and methods: 52 patients with breast cancer who attended AIIMS Bhopal from November 2018 to January 2020 were selected, with their clinical details, triple assessment and other investigations for further management being performed and recorded. The presence of uterine fibroids was assessed using ultrasound of the abdomen, and for patients who had undergone hysterectomy, previous medical records were examined to ascertain the history of uterine fibroids. Serum levels of estrogen and progesterone were assessed using chemi-luminescent micro-particle immune assay (CMIA). Results: The mean age of patients was 50.35 ± 10.87 years. 36.54% of our patients had uterine fibroids, of whom 15.38% had undergone hysterectomy for the same, and 21.15% was detected on ultrasound of the abdomen during evaluation. Among patients with uterine fibroids, 84.2% were hormone receptor-positive, while in patients without uterine fibroids, only 57.6% had positive receptors. (P = 0.049). Among premenopausal patients, there was a statistically significant difference in serum progesterone values between patients with and without uterine fibroids. Conclusion: The prevalence of uterine fibroids in our study group of breast cancer patients was found to be high. The role of estrogen and progesterone in the pathophysiology of both diseases and the common risk factors involved may biologically explain this finding. Breast cancer and other estrogen associated disorders may hold future research prospects.
{"title":"A Study on Clinico-Pathological Profile of Breast Cancer Patients and Their Correlation With Uterine Fibroids Using Hormone Level and Receptor Status Assessment","authors":"A. Mohan, Vinay Kumar, S. Brahmachari, B. Pandya","doi":"10.1177/11782234221090197","DOIUrl":"https://doi.org/10.1177/11782234221090197","url":null,"abstract":"Purpose: To study the clinico-pathological profile of breast cancer patients and the prevalence of uterine fibroids in them, their hormonal levels and hormone receptor status. Patients and methods: 52 patients with breast cancer who attended AIIMS Bhopal from November 2018 to January 2020 were selected, with their clinical details, triple assessment and other investigations for further management being performed and recorded. The presence of uterine fibroids was assessed using ultrasound of the abdomen, and for patients who had undergone hysterectomy, previous medical records were examined to ascertain the history of uterine fibroids. Serum levels of estrogen and progesterone were assessed using chemi-luminescent micro-particle immune assay (CMIA). Results: The mean age of patients was 50.35 ± 10.87 years. 36.54% of our patients had uterine fibroids, of whom 15.38% had undergone hysterectomy for the same, and 21.15% was detected on ultrasound of the abdomen during evaluation. Among patients with uterine fibroids, 84.2% were hormone receptor-positive, while in patients without uterine fibroids, only 57.6% had positive receptors. (P = 0.049). Among premenopausal patients, there was a statistically significant difference in serum progesterone values between patients with and without uterine fibroids. Conclusion: The prevalence of uterine fibroids in our study group of breast cancer patients was found to be high. The role of estrogen and progesterone in the pathophysiology of both diseases and the common risk factors involved may biologically explain this finding. Breast cancer and other estrogen associated disorders may hold future research prospects.","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"34 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88269195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/11782234221092155
J. Endrikat, G. Schmidt, D. Haverstock, Olaf Weber, Z. Trnkova, J. Barkhausen
Background: The impact of certain tumor parameters on the sensitivity of imaging tools is unknown. The purpose was to study the impact of breast cancer histology, tumor grading, single receptor status, and molecular subtype on the sensitivity of contrast-enhanced breast magnetic resonance imaging (CE-BMRI) vs X-ray mammography (XRM) to detect breast cancer. Materials and Methods: We ran a supplemental analysis of 2 global Phase III studies which recruited patients with histologically proven breast cancers. The sensitivity of CE-BMRI vs XRM to detect cancer lesions with different histologies, tumor grading, single receptor status, and molecular subtype was compared. Six blinded readers for each study evaluated the images. Results were summarized as the “Mean Reader.” For each reader, sensitivity was defined as the proportion of detected lesions vs the total number of lesions identified by the standard of reference. Two-sided 95% confidence intervals were calculated for within-group proportions, and for the difference between CE-BMRI and XRM, using a normal approximation to the binomial distribution. Results: In 778 patients, 1273 cancer lesions were detected. A total of 435 patients had 1 lesion, 254 had 2 lesions, and 77 had 3 or more lesions. The sensitivity of CE-BMRI was significantly higher compared with XRM irrespective of the histology. The largest difference was seen for invasive lobular carcinoma (22.3%) and ductal carcinoma in situ (19%). Across all 3 tumor grades, the sensitivity advantage of CE-BMRI over XRM ranged from 15.7% to 18.5%. Contrast-enhanced breast magnetic resonance imaging showed higher sensitivity compared with XRM irrespective of single receptor expressions (15.3%-19.4%). The sensitivities for both imaging methods were numerically higher for the more aggressive ER– (estrogen receptor), PR– (progesterone receptor), and HER2+ (human epidermal growth factor receptor 2) tumors. Irrespective of molecular subtype, sensitivity of CE-BMRI was 14.8% to 18.9% higher compared with XRM. Conclusions: Contrast-enhanced breast magnetic resonance imaging showed significantly higher sensitivity compared with XRM independent of tumor histology, tumor grading, single receptor status, and molecular subtype. Trial Registration: ClinicalTrials.gov: NCT01067976 and NCT01104584.
{"title":"Sensitivity of Contrast-Enhanced Breast MRI vs X-ray Mammography Based on Cancer Histology, Tumor Grading, Receptor Status, and Molecular Subtype: A Supplemental Analysis of 2 Large Phase III Studies","authors":"J. Endrikat, G. Schmidt, D. Haverstock, Olaf Weber, Z. Trnkova, J. Barkhausen","doi":"10.1177/11782234221092155","DOIUrl":"https://doi.org/10.1177/11782234221092155","url":null,"abstract":"Background: The impact of certain tumor parameters on the sensitivity of imaging tools is unknown. The purpose was to study the impact of breast cancer histology, tumor grading, single receptor status, and molecular subtype on the sensitivity of contrast-enhanced breast magnetic resonance imaging (CE-BMRI) vs X-ray mammography (XRM) to detect breast cancer. Materials and Methods: We ran a supplemental analysis of 2 global Phase III studies which recruited patients with histologically proven breast cancers. The sensitivity of CE-BMRI vs XRM to detect cancer lesions with different histologies, tumor grading, single receptor status, and molecular subtype was compared. Six blinded readers for each study evaluated the images. Results were summarized as the “Mean Reader.” For each reader, sensitivity was defined as the proportion of detected lesions vs the total number of lesions identified by the standard of reference. Two-sided 95% confidence intervals were calculated for within-group proportions, and for the difference between CE-BMRI and XRM, using a normal approximation to the binomial distribution. Results: In 778 patients, 1273 cancer lesions were detected. A total of 435 patients had 1 lesion, 254 had 2 lesions, and 77 had 3 or more lesions. The sensitivity of CE-BMRI was significantly higher compared with XRM irrespective of the histology. The largest difference was seen for invasive lobular carcinoma (22.3%) and ductal carcinoma in situ (19%). Across all 3 tumor grades, the sensitivity advantage of CE-BMRI over XRM ranged from 15.7% to 18.5%. Contrast-enhanced breast magnetic resonance imaging showed higher sensitivity compared with XRM irrespective of single receptor expressions (15.3%-19.4%). The sensitivities for both imaging methods were numerically higher for the more aggressive ER– (estrogen receptor), PR– (progesterone receptor), and HER2+ (human epidermal growth factor receptor 2) tumors. Irrespective of molecular subtype, sensitivity of CE-BMRI was 14.8% to 18.9% higher compared with XRM. Conclusions: Contrast-enhanced breast magnetic resonance imaging showed significantly higher sensitivity compared with XRM independent of tumor histology, tumor grading, single receptor status, and molecular subtype. Trial Registration: ClinicalTrials.gov: NCT01067976 and NCT01104584.","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"3 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75311709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/11782234211070217
Maxwell C. Braasch, Amanda L. Amin, Christa R. Balanoff, J. Wagner, K. Larson
Purpose: Women with lobular carcinoma in-situ (LCIS) have an increased risk for developing breast cancer (BC) compared with the general population. However, little is known about the clinical implication of diagnosing LCIS concurrently with an invasive breast cancer. We aimed to define the rate of LCIS diagnosed concurrently with an invasive breast cancer and investigate the risk of contralateral breast cancer (CBC) during survivorship care. Materials and methods: A single center retrospective review over 6 years identified women with stage I-III BC who underwent lumpectomy or unilateral mastectomy. Patients with or without concurrent LCIS were compared using Chi-squared analyses to assess for differences in clinicopathologic factors and risk of future CBC (including invasive and in-situ disease). Results: Of 1808 patients, 16.6% (n = 301) had LCIS concurrent with their index breast cancer. Patients with LCIS had a higher rate of subsequent CBC development than those without LCIS (3.3% versus 1.0%, P = .004). The risk ratio for patients with LCIS developing subsequent CBC compared with those without LCIS was 3.3 (95% confidence interval [CI]: 1.5-7.3). Conclusions: Patients with LCIS diagnosed concurrently with their index breast cancer at surgery are at higher risk for subsequent CBC than those without LCIS. The evidence from this study suggest that it may be appropriate for women with LCIS diagnosed alongside an index breast cancer to consider on-going high-risk screening during survivorship care.
{"title":"Prognostic Significance of Lobular Carcinoma In-Situ (LCIS) Diagnosed Alongside Invasive Breast Cancer","authors":"Maxwell C. Braasch, Amanda L. Amin, Christa R. Balanoff, J. Wagner, K. Larson","doi":"10.1177/11782234211070217","DOIUrl":"https://doi.org/10.1177/11782234211070217","url":null,"abstract":"Purpose: Women with lobular carcinoma in-situ (LCIS) have an increased risk for developing breast cancer (BC) compared with the general population. However, little is known about the clinical implication of diagnosing LCIS concurrently with an invasive breast cancer. We aimed to define the rate of LCIS diagnosed concurrently with an invasive breast cancer and investigate the risk of contralateral breast cancer (CBC) during survivorship care. Materials and methods: A single center retrospective review over 6 years identified women with stage I-III BC who underwent lumpectomy or unilateral mastectomy. Patients with or without concurrent LCIS were compared using Chi-squared analyses to assess for differences in clinicopathologic factors and risk of future CBC (including invasive and in-situ disease). Results: Of 1808 patients, 16.6% (n = 301) had LCIS concurrent with their index breast cancer. Patients with LCIS had a higher rate of subsequent CBC development than those without LCIS (3.3% versus 1.0%, P = .004). The risk ratio for patients with LCIS developing subsequent CBC compared with those without LCIS was 3.3 (95% confidence interval [CI]: 1.5-7.3). Conclusions: Patients with LCIS diagnosed concurrently with their index breast cancer at surgery are at higher risk for subsequent CBC than those without LCIS. The evidence from this study suggest that it may be appropriate for women with LCIS diagnosed alongside an index breast cancer to consider on-going high-risk screening during survivorship care.","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"15 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82374827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/11782234221086713
A. Shatnawi, N. Ayoub, Amer E. Alkhalifa, D. R. Ibrahim
Purpose: It has been suggested that dysregulation of transcription factors expression or activity plays significant roles in breast cancer (BC) severity and poor prognosis. Therefore, our study aims to thoroughly evaluate the estrogen-related receptor isoforms (ESRRs) expression and copy number alteration (CNA) status and their association with clinicopathologic characteristics in BC. Methods: A METABRIC dataset consist of 2509 BC patients’ samples was obtained from the cBioPortal public domain. The gene expression, putative CNA, and relevant tumor information of ESRRs were retrieved. ESRRs messenger RNA (mRNA) expression in BC cell lines was obtained from the Cancer Cell Line Encyclopedia (CCLE). Association and correlation analysis of ESRRs expression with BC clinicopathologic characteristics and molecular subtype were performed. Kaplan–Meier survival analysis was conducted to evaluate the prognostic value of ESRRs expression on patient survival. Results: ESRRα expression correlated negatively with patients’ age and overall survival, whereas positively correlated with tumor size, the number of positive lymph nodes, and Nottingham prognostic index (NPI). Conversely, ESRRγ expression was positively correlated with patients’ age and negatively correlated with NPI. ESRRα and ESRRγ expression were significantly associated with tumor grade, expression of hormone receptors, human epidermal growth factor receptor 2 (HER2), and molecular subtype, whereas ESRRβ was only associated with tumor stage. A significant and distinct association of each of ESRRs CNA with various clinicopathologic and prognostic factors was also observed. Kaplan–Meier survival analysis demonstrated no significant difference for survival curves among BC patients with high or low expression of ESRRα, β, or γ. On stratification, high ESRRα expression significantly reduced survival among premenopausal patients, patients with grade I/II, and early-stage disease. In BC cell lines, only ESRRα expression was significantly higher in HER2-positive cells. No significant association was observed between ESRRβ expression and any of the clinicopathologic characteristics examined. Conclusions: In this clinical dataset, ESRRα and ESRRγ mRNA expression and CNA show a significant correlation and association with distinct clinicopathologic and prognostic parameters known to influence treatment outcomes; however, ESRRβ failed to show a robust role in BC pathogenesis. ESRRα and ESRRγ can be employed as therapeutic targets in BC-targeted therapy. However, the role of ESRRβ in BC pathogenesis remains unclear.
目的:研究表明，转录因子表达或活性的失调在乳腺癌(BC)严重程度和不良预后中起着重要作用。因此，我们的研究旨在全面评估雌激素相关受体亚型(esrr)表达和拷贝数改变(CNA)状态及其与BC临床病理特征的关系。方法:从cBioPortal公共领域获得包含2509例BC患者样本的METABRIC数据集。检索esrr的基因表达、推测的CNA和相关肿瘤信息。ESRRs信使RNA (mRNA)在BC细胞系中的表达量来源于Cancer cell Line Encyclopedia (CCLE)。分析ESRRs表达与BC临床病理特征及分子亚型的相关性。通过Kaplan-Meier生存分析来评估ESRRs表达对患者生存的预后价值。结果:ESRRα表达与患者年龄、总生存期呈负相关，与肿瘤大小、阳性淋巴结数、诺丁汉预后指数(NPI)呈正相关。相反，ESRRγ表达与患者年龄正相关，与NPI负相关。ESRRα和ESRRγ的表达与肿瘤分级、激素受体、人表皮生长因子受体2 (HER2)的表达和分子亚型显著相关，而ESRRβ仅与肿瘤分期相关。我们还观察到，每个esrr CNA与各种临床病理和预后因素之间存在显著且独特的关联。Kaplan-Meier生存分析显示，ESRRα、β或γ高表达或低表达的BC患者的生存曲线无显著差异。在分层研究中，高ESRRα表达显著降低了绝经前患者、I/II级患者和早期疾病患者的生存率。在BC细胞系中，her2阳性细胞中只有ESRRα表达显著升高。未观察到ESRRβ表达与所检查的任何临床病理特征之间存在显著关联。结论:在该临床数据集中，ESRRα和ESRRγ mRNA表达和CNA与已知影响治疗结果的不同临床病理和预后参数具有显著相关性和相关性;然而，ESRRβ未能在BC发病机制中显示出强大的作用。ESRRα和ESRRγ可作为bc靶向治疗的治疗靶点。然而，ESRRβ在BC发病机制中的作用尚不清楚。
{"title":"Estrogen-Related Receptors Gene Expression and Copy Number Alteration Association With the Clinicopathologic Characteristics of Breast Cancer","authors":"A. Shatnawi, N. Ayoub, Amer E. Alkhalifa, D. R. Ibrahim","doi":"10.1177/11782234221086713","DOIUrl":"https://doi.org/10.1177/11782234221086713","url":null,"abstract":"Purpose: It has been suggested that dysregulation of transcription factors expression or activity plays significant roles in breast cancer (BC) severity and poor prognosis. Therefore, our study aims to thoroughly evaluate the estrogen-related receptor isoforms (ESRRs) expression and copy number alteration (CNA) status and their association with clinicopathologic characteristics in BC. Methods: A METABRIC dataset consist of 2509 BC patients’ samples was obtained from the cBioPortal public domain. The gene expression, putative CNA, and relevant tumor information of ESRRs were retrieved. ESRRs messenger RNA (mRNA) expression in BC cell lines was obtained from the Cancer Cell Line Encyclopedia (CCLE). Association and correlation analysis of ESRRs expression with BC clinicopathologic characteristics and molecular subtype were performed. Kaplan–Meier survival analysis was conducted to evaluate the prognostic value of ESRRs expression on patient survival. Results: ESRRα expression correlated negatively with patients’ age and overall survival, whereas positively correlated with tumor size, the number of positive lymph nodes, and Nottingham prognostic index (NPI). Conversely, ESRRγ expression was positively correlated with patients’ age and negatively correlated with NPI. ESRRα and ESRRγ expression were significantly associated with tumor grade, expression of hormone receptors, human epidermal growth factor receptor 2 (HER2), and molecular subtype, whereas ESRRβ was only associated with tumor stage. A significant and distinct association of each of ESRRs CNA with various clinicopathologic and prognostic factors was also observed. Kaplan–Meier survival analysis demonstrated no significant difference for survival curves among BC patients with high or low expression of ESRRα, β, or γ. On stratification, high ESRRα expression significantly reduced survival among premenopausal patients, patients with grade I/II, and early-stage disease. In BC cell lines, only ESRRα expression was significantly higher in HER2-positive cells. No significant association was observed between ESRRβ expression and any of the clinicopathologic characteristics examined. Conclusions: In this clinical dataset, ESRRα and ESRRγ mRNA expression and CNA show a significant correlation and association with distinct clinicopathologic and prognostic parameters known to influence treatment outcomes; however, ESRRβ failed to show a robust role in BC pathogenesis. ESRRα and ESRRγ can be employed as therapeutic targets in BC-targeted therapy. However, the role of ESRRβ in BC pathogenesis remains unclear.","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"528 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77877115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/11782234221095897
Eduardo de Faria Castro Fleury, Caio Castro, Mario Sergio Campos do Amaral, Décio Roveda Júnior
Rationale and Objectives: According to the Breast Imaging and Reporting Data System (BI-RADS), one of the main limitations of MRI is diagnosing the non-mass enhancement (NME). The NME lesion is challenging since it is unique to the MRI lexicon. This study aims to report our experience with NME lesions diagnosed by MRI referred for MRI-guided biopsies and discuss the management and follow-up of these lesions. Materials and Methods: We retrospectively evaluated all MRI-guide breast biopsies. We included all patients referred for NME breast MRI-guided biopsy in screening settings. All patients had a negative second-look mammography or ultrasonography. We correlated the distribution and internal enhancement pattern (IEP) of the NME lesions with histology. Invasive ductal carcinomas (IDC) of no special type and ductal carcinoma in situ (DCIS) were considered malignant lesions. Results: From January-2018 to July-2021, we included 96 women with a total of 96 lesions in the study. There were 90 benign and 6 malignant lesions with DCIS prevalence (5/6 cancers). The most frequent benign lesion type was fibrocystic changes. There were no NME lesions with diffuse or multiple area distribution features referred to MRI-guided biopsy. The positive-predictive values (PPV) were respectively 0.0%, 2.5%, 9.0%, and 11.0% for linear, focal, regional, and segmental distribution describers, and 0.0, 3.0%, 7.9%, and 50% for homogenous, heterogeneous, clumped, and clustered-ring enhancement patterns. Conclusion: We observe the high potential risk for malignancy in the clustered-ring enhancement followed by the clumped pattern. Segmental distribution presented the highest predictive-positive values.
{"title":"Management of Non-Mass Enhancement at Breast Magnetic Resonance in Screening Settings Referred for Magnetic Resonance-Guided Biopsy","authors":"Eduardo de Faria Castro Fleury, Caio Castro, Mario Sergio Campos do Amaral, Décio Roveda Júnior","doi":"10.1177/11782234221095897","DOIUrl":"https://doi.org/10.1177/11782234221095897","url":null,"abstract":"Rationale and Objectives: According to the Breast Imaging and Reporting Data System (BI-RADS), one of the main limitations of MRI is diagnosing the non-mass enhancement (NME). The NME lesion is challenging since it is unique to the MRI lexicon. This study aims to report our experience with NME lesions diagnosed by MRI referred for MRI-guided biopsies and discuss the management and follow-up of these lesions. Materials and Methods: We retrospectively evaluated all MRI-guide breast biopsies. We included all patients referred for NME breast MRI-guided biopsy in screening settings. All patients had a negative second-look mammography or ultrasonography. We correlated the distribution and internal enhancement pattern (IEP) of the NME lesions with histology. Invasive ductal carcinomas (IDC) of no special type and ductal carcinoma in situ (DCIS) were considered malignant lesions. Results: From January-2018 to July-2021, we included 96 women with a total of 96 lesions in the study. There were 90 benign and 6 malignant lesions with DCIS prevalence (5/6 cancers). The most frequent benign lesion type was fibrocystic changes. There were no NME lesions with diffuse or multiple area distribution features referred to MRI-guided biopsy. The positive-predictive values (PPV) were respectively 0.0%, 2.5%, 9.0%, and 11.0% for linear, focal, regional, and segmental distribution describers, and 0.0, 3.0%, 7.9%, and 50% for homogenous, heterogeneous, clumped, and clustered-ring enhancement patterns. Conclusion: We observe the high potential risk for malignancy in the clustered-ring enhancement followed by the clumped pattern. Segmental distribution presented the highest predictive-positive values.","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84844451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/11782234221086728
M. A. Askar, H. El-Nashar, Mahmood A Al-Azzawi, Sahar S Abdel Rahman, Omama E. Elshawi
Quercetin is a potent cancer therapeutic agent present in fruits and vegetables. The pharmaceutical uses of quercetin are limited due to many problems associated with low solubility, bioavailability, permeability, and instability. In addition, the high doses of quercetin show toxic effects in clinical and experimental studies. Therefore, a new strategy is warranted to overcome these problems without the use of toxic doses. The iron oxide nanoparticles can be used as a drug delivery system. This study aimed to prepare quercetin-conjugated magnetite nanoparticles (QMNPs) using biological simple nanoprecipitation and mediated by fungus Aspergillus oryzae. Also, we initiated in vitro and in vivo studies to determine whether QMNPs might sensitize breast cancer to radiotherapy treatment. The structural, morphological, and magnetic properties of the prepared nanoparticles were studied. The results indicated that QMNPs were spherical in shape and 40 nm in diameter. The in vitro studies showed that the incubation of MCF-7, HePG-2, and A459 cancer cells with QMNPs for 24 h effectively inhibited the growth of cancer cell lines in a concentration-dependent manner with IC50 values of 11, 77.5, and104 nmol/mL, respectively. The combination of QMNPs with irradiation (IR) potently blocked MCF-7 cancer cell proliferation and showed significant changes in the morphology of these cells as observed by bright-field inverted light microscopy. Focusing on the long-term toxicity of QMNPs (20 ml/kg), the assessment of hematological, hepatic, and renal markers indicated no toxic effect. Besides, QMNPs inhibited tumor growth and potently enhanced the lateral radiotherapy treatment in N-methyl-N-nitrosourea (MNU)-induced breast cancer in female white albino rats. These anticancer and radiosensitizing activities were ascribed to cytotoxicity, cell cycle arrest, immunomodulation, and efficiency through induction of apoptosis. In a conclusion, these observations suggest that the QMNPs combined with LRT could act as a potential targeted therapy in breast cancer.
{"title":"Synergistic Effect of Quercetin Magnetite Nanoparticles and Targeted Radiotherapy in Treatment of Breast Cancer","authors":"M. A. Askar, H. El-Nashar, Mahmood A Al-Azzawi, Sahar S Abdel Rahman, Omama E. Elshawi","doi":"10.1177/11782234221086728","DOIUrl":"https://doi.org/10.1177/11782234221086728","url":null,"abstract":"Quercetin is a potent cancer therapeutic agent present in fruits and vegetables. The pharmaceutical uses of quercetin are limited due to many problems associated with low solubility, bioavailability, permeability, and instability. In addition, the high doses of quercetin show toxic effects in clinical and experimental studies. Therefore, a new strategy is warranted to overcome these problems without the use of toxic doses. The iron oxide nanoparticles can be used as a drug delivery system. This study aimed to prepare quercetin-conjugated magnetite nanoparticles (QMNPs) using biological simple nanoprecipitation and mediated by fungus Aspergillus oryzae. Also, we initiated in vitro and in vivo studies to determine whether QMNPs might sensitize breast cancer to radiotherapy treatment. The structural, morphological, and magnetic properties of the prepared nanoparticles were studied. The results indicated that QMNPs were spherical in shape and 40 nm in diameter. The in vitro studies showed that the incubation of MCF-7, HePG-2, and A459 cancer cells with QMNPs for 24 h effectively inhibited the growth of cancer cell lines in a concentration-dependent manner with IC50 values of 11, 77.5, and104 nmol/mL, respectively. The combination of QMNPs with irradiation (IR) potently blocked MCF-7 cancer cell proliferation and showed significant changes in the morphology of these cells as observed by bright-field inverted light microscopy. Focusing on the long-term toxicity of QMNPs (20 ml/kg), the assessment of hematological, hepatic, and renal markers indicated no toxic effect. Besides, QMNPs inhibited tumor growth and potently enhanced the lateral radiotherapy treatment in N-methyl-N-nitrosourea (MNU)-induced breast cancer in female white albino rats. These anticancer and radiosensitizing activities were ascribed to cytotoxicity, cell cycle arrest, immunomodulation, and efficiency through induction of apoptosis. In a conclusion, these observations suggest that the QMNPs combined with LRT could act as a potential targeted therapy in breast cancer.","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"1 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77095918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/11782234221089597
Ilias G. Petrou, C. Thomet, Omid Jamei, A. Modarressi, D. Kalbermatten, B. Pittet‐Cuenod
Background: An increasing number of breast cancer patients undergo immediate or secondary breast reconstruction, but the ideal method in terms of patient satisfaction remains ambiguous. We compared the 3 most common breast reconstruction techniques to determine patient satisfaction and objective outcomes. Methods: Retrospective study of 184 patients with breast cancer who underwent a reconstructive procedure between 1993 and 2011 at our institution. Procedures evaluated were implant-based reconstruction (IBR) alone, latissimus dorsi (LD) flap reconstruction with/without implant, and deep inferior epigastric perforator (DIEP) free flap reconstruction. A retrospective patient satisfaction questionnaire was sent to all women. Twenty patients from each subgroup were matched to conduct a standardized objective assessment of the sensitivity of their reconstructed breast. A blinded photographic evaluation was also performed by 3 independent observers to assess the esthetic aspect and symmetry. Results: DIEP obtained significantly higher average scores regarding the esthetic outcome, immediate reconstruction impact, and overall score in the questionnaire evaluation. The IBR had the best results in the somatosensory evaluation, with DIEP scoring better than LD. DIEP received higher scores on average than LD for the criteria of size and symmetry in the esthetic evaluation. No statistically significant differences were observed between IBR and DIEP. Conclusions: Good results were reported overall for all breast reconstruction procedures, with more reserved scores for LD. The DIEP reconstruction appeared to be the most satisfactory and best experienced reconstruction method for patients, despite the complexity of the intervention. Clinicians should be encouraged to consider DIEP as the principal choice for breast reconstruction.
{"title":"Defining the Ideal Breast Reconstruction Procedure After Mastectomy From the Patient Perspective: A Retrospective Analysis","authors":"Ilias G. Petrou, C. Thomet, Omid Jamei, A. Modarressi, D. Kalbermatten, B. Pittet‐Cuenod","doi":"10.1177/11782234221089597","DOIUrl":"https://doi.org/10.1177/11782234221089597","url":null,"abstract":"Background: An increasing number of breast cancer patients undergo immediate or secondary breast reconstruction, but the ideal method in terms of patient satisfaction remains ambiguous. We compared the 3 most common breast reconstruction techniques to determine patient satisfaction and objective outcomes. Methods: Retrospective study of 184 patients with breast cancer who underwent a reconstructive procedure between 1993 and 2011 at our institution. Procedures evaluated were implant-based reconstruction (IBR) alone, latissimus dorsi (LD) flap reconstruction with/without implant, and deep inferior epigastric perforator (DIEP) free flap reconstruction. A retrospective patient satisfaction questionnaire was sent to all women. Twenty patients from each subgroup were matched to conduct a standardized objective assessment of the sensitivity of their reconstructed breast. A blinded photographic evaluation was also performed by 3 independent observers to assess the esthetic aspect and symmetry. Results: DIEP obtained significantly higher average scores regarding the esthetic outcome, immediate reconstruction impact, and overall score in the questionnaire evaluation. The IBR had the best results in the somatosensory evaluation, with DIEP scoring better than LD. DIEP received higher scores on average than LD for the criteria of size and symmetry in the esthetic evaluation. No statistically significant differences were observed between IBR and DIEP. Conclusions: Good results were reported overall for all breast reconstruction procedures, with more reserved scores for LD. The DIEP reconstruction appeared to be the most satisfactory and best experienced reconstruction method for patients, despite the complexity of the intervention. Clinicians should be encouraged to consider DIEP as the principal choice for breast reconstruction.","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"77 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89767439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/11782234221086992
Alan Celik, T. Berg, L. B. Nielsen, M. Jensen, B. Ejlertsen, Ann S. Knoop, M. Andersson
Purpose: Dual blockade with trastuzumab and pertuzumab in combination with chemotherapy is the recommended first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). The purpose of this retrospective study is to examine the clinical outcomes of the trastuzumab biosimilar SB3 in first-line dual blockade treatment using real-world data of patients with HER-positive mBC. Methods: In Denmark, all women with breast cancer are registered in the database of the Danish Breast Cancer Group (DBCG). From this prospective observational registry, we extracted information on primary diagnosis and treatment of all women with HER2-positive mBC who received first-line treatment with SB3 and pertuzumab from September 1, 2018, to February 29, 2020. Retrospectively collected data from the DBCG database included information concerning treatment start, end, and reason for discontinuation. The primary endpoints for the study were overall survival (OS) and progression-free survival (PFS). Results: The study included 117 women who received first-line treatment with SB3 and pertuzumab for their HER2-positive mBC. The study population had a mean age of 60 years. A total of 71 patients (61%) had recurrent disease and 46 patients (39%) presented with de novo mBC. The median follow-up was 11.1 and 15.4 months for PFS and OS, respectively. At 12 months, OS was 84% (95% confidence interval [CI], 78-91), whereas the median OS was not reached. The median PFS was 12.7 months (95% CI, 11.1-16.2). Median time on treatment was 8.7 months (95% CI, 7.6-11.4); 36 patients (31%) were still on treatment at end of study. Conclusions: This retrospective real-world, nationwide study demonstrated comparable median PFS to the historical data of using reference trastuzumab and pertuzumab as first-line dual blockade.
{"title":"First-Line Treatment of HER2-Positive Metastatic Breast Cancer With Dual Blockade Including Biosimilar Trastuzumab (SB3): Population-Based Real-World Data From the DBCG","authors":"Alan Celik, T. Berg, L. B. Nielsen, M. Jensen, B. Ejlertsen, Ann S. Knoop, M. Andersson","doi":"10.1177/11782234221086992","DOIUrl":"https://doi.org/10.1177/11782234221086992","url":null,"abstract":"Purpose: Dual blockade with trastuzumab and pertuzumab in combination with chemotherapy is the recommended first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). The purpose of this retrospective study is to examine the clinical outcomes of the trastuzumab biosimilar SB3 in first-line dual blockade treatment using real-world data of patients with HER-positive mBC. Methods: In Denmark, all women with breast cancer are registered in the database of the Danish Breast Cancer Group (DBCG). From this prospective observational registry, we extracted information on primary diagnosis and treatment of all women with HER2-positive mBC who received first-line treatment with SB3 and pertuzumab from September 1, 2018, to February 29, 2020. Retrospectively collected data from the DBCG database included information concerning treatment start, end, and reason for discontinuation. The primary endpoints for the study were overall survival (OS) and progression-free survival (PFS). Results: The study included 117 women who received first-line treatment with SB3 and pertuzumab for their HER2-positive mBC. The study population had a mean age of 60 years. A total of 71 patients (61%) had recurrent disease and 46 patients (39%) presented with de novo mBC. The median follow-up was 11.1 and 15.4 months for PFS and OS, respectively. At 12 months, OS was 84% (95% confidence interval [CI], 78-91), whereas the median OS was not reached. The median PFS was 12.7 months (95% CI, 11.1-16.2). Median time on treatment was 8.7 months (95% CI, 7.6-11.4); 36 patients (31%) were still on treatment at end of study. Conclusions: This retrospective real-world, nationwide study demonstrated comparable median PFS to the historical data of using reference trastuzumab and pertuzumab as first-line dual blockade.","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"1 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74541306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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