Pub Date : 2024-10-27eCollection Date: 2024-01-01DOI: 10.1177/11782234241288671
Momoko Tokura, Mark Malalay Ando, Yuki Kojima, Rui Kitadai, Shu Yazaki, Cyrielle Marie N Atutubo, Rubi K Li, Minda Z Perez, Agnes E Gorospe, Manuelito A Madrid, Mel Valerie C Ordinario, Marcelo Severino B Imasa, Kazuki Sudo, Tatsunori Shimoi, Akihiko Suto, Shinji Kohsaka, Ryunosuke Machida, Ryo Sadachi, Masayuki Yoshida, Yasushi Yatabe, Tomomi Hata, Kenichi Nakamura, Kan Yonemori, Sho Shiino
Background: Biomarkers to predict the recurrence risk are required to optimize perioperative treatment. Adjuvant chemotherapy for patients with human epidermal growth factor 2-positive (HER2-positive) early breast cancer is decided by pathological responses of neoadjuvant chemotherapy (NAC). However, whether pathological responses are appropriate biomarkers is unclear. Currently, there are several studies using minimal residual disease (MRD) as a predictor of prognosis in solid tumors. However, there is no standard method for detecting MRD.
Objectives: This study aimed at prospectively evaluating the relationship between MRD detection and recurrence in Asian patients with HER2-positive early breast cancer.
Design: Prospective, observational, single-group, and exploratory. This study will include 60 patients from 2 institutions in Japan and the Philippines. The invasive disease-free survival (IDFS) rates of the MRD-positive and MRD-negative groups are compared in patients with HER2-positive early breast cancer who undergo surgery after receiving NAC.
Methods and analysis: Circulating tumor DNA (ctDNA) levels of patients will be evaluated 6 times: before NAC, after NAC, after surgery, and annually after surgery for 3 years. We will analyze the genetic profile of blood and tissue samples using the Todai OncoPanel (TOP) and the methylation level of DNA. The primary endpoint is IDFS. Secondary endpoints include overall survival (OS) and disease-free survival (DFS). Patient enrollment began in June 2022, and new participants are still being recruited.
Ethics: This study has been approved by the National Cancer Center Hospital Certified Review Board in March 2022 and has been approved by the Research Ethics Board of the participating center.
Discussion: Our findings will contribute to determining whether MRD detection using TOP is useful for predicting the recurrence of HER2-positive early breast cancer. If this is proven, MRD detected by TOP could be used in the future as a biomarker to assist in the de-/escalation of treatment strategies in the next interventional trial, thereby avoiding overtreatment in patients at low risk, and in the addition of intensive treatment modalities for those in patients at high risk.
{"title":"Multicenter Prospective Study in HER2-Positive Early Breast Cancer for Detecting Minimal Residual Disease by Circulating Tumor DNA Analysis With Neoadjuvant Chemotherapy: HARMONY Study.","authors":"Momoko Tokura, Mark Malalay Ando, Yuki Kojima, Rui Kitadai, Shu Yazaki, Cyrielle Marie N Atutubo, Rubi K Li, Minda Z Perez, Agnes E Gorospe, Manuelito A Madrid, Mel Valerie C Ordinario, Marcelo Severino B Imasa, Kazuki Sudo, Tatsunori Shimoi, Akihiko Suto, Shinji Kohsaka, Ryunosuke Machida, Ryo Sadachi, Masayuki Yoshida, Yasushi Yatabe, Tomomi Hata, Kenichi Nakamura, Kan Yonemori, Sho Shiino","doi":"10.1177/11782234241288671","DOIUrl":"10.1177/11782234241288671","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers to predict the recurrence risk are required to optimize perioperative treatment. Adjuvant chemotherapy for patients with human epidermal growth factor 2-positive (HER2-positive) early breast cancer is decided by pathological responses of neoadjuvant chemotherapy (NAC). However, whether pathological responses are appropriate biomarkers is unclear. Currently, there are several studies using minimal residual disease (MRD) as a predictor of prognosis in solid tumors. However, there is no standard method for detecting MRD.</p><p><strong>Objectives: </strong>This study aimed at prospectively evaluating the relationship between MRD detection and recurrence in Asian patients with HER2-positive early breast cancer.</p><p><strong>Design: </strong>Prospective, observational, single-group, and exploratory. This study will include 60 patients from 2 institutions in Japan and the Philippines. The invasive disease-free survival (IDFS) rates of the MRD-positive and MRD-negative groups are compared in patients with HER2-positive early breast cancer who undergo surgery after receiving NAC.</p><p><strong>Methods and analysis: </strong>Circulating tumor DNA (ctDNA) levels of patients will be evaluated 6 times: before NAC, after NAC, after surgery, and annually after surgery for 3 years. We will analyze the genetic profile of blood and tissue samples using the Todai OncoPanel (TOP) and the methylation level of DNA. The primary endpoint is IDFS. Secondary endpoints include overall survival (OS) and disease-free survival (DFS). Patient enrollment began in June 2022, and new participants are still being recruited.</p><p><strong>Ethics: </strong>This study has been approved by the National Cancer Center Hospital Certified Review Board in March 2022 and has been approved by the Research Ethics Board of the participating center.</p><p><strong>Discussion: </strong>Our findings will contribute to determining whether MRD detection using TOP is useful for predicting the recurrence of HER2-positive early breast cancer. If this is proven, MRD detected by TOP could be used in the future as a biomarker to assist in the de-/escalation of treatment strategies in the next interventional trial, thereby avoiding overtreatment in patients at low risk, and in the addition of intensive treatment modalities for those in patients at high risk.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567099","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 : 2024-10-19eCollection Date: 2024-01-01DOI: 10.1177/11782234241285648
Athina Giannoudis, Alistair Heath, Vijay Sharma
Background: Metabolic reprogramming is one of the hallmarks of cancer, and in breast cancer (BC), several metabolic enzymes are overexpressed and overactivated. One of these, Enolase 1 (ENO1), catalyses glycolysis and is involved in the regulation of multiple signalling pathways.
Objectives: This study aimed to evaluate in silico the prognostic and predictive effects of ENO1 expression in BC.
Design: This is a bioinformatic in silico analysis.
Methods: Using available online platforms (Kaplan-Meier [KM] plotter, receiver operating characteristic curve [ROC] plotter, cBioPortal, Genotype-2-Outcome [G-2-O], MethSurv, and Tumour-Immune System Interaction Database [TISIDB]), we performed a bioinformatic in silico analysis to establish the prognostic and predictive effects related to ENO1 expression in BC. A network analysis was performed using the Oncomine platform, and signalling, epigenetic, and immune regulation pathways were explored.
Results: ENO1 was overexpressed in all the analysed Oncomine, epigenetic, and immune pathways in triple-negative, but not in hormone receptor-positive BCs. In human epidermal growth factor receptor 2 (HER2)-positive BCs, ENO1 expression showed a mixed profile. Analysis on disease progression and histological types showed ENO1 overexpression in ductal in situ and invasive carcinoma, in high-grade tumours followed by advanced or metastasis and was linked to worse survival. High ENO1 expression was also associated with relapse-free, distant metastasis-free and overall survival, irrespectively of treatment and was mainly related to basal subtype.
Conclusion: ENO1 overexpression recruits a range of signalling pathways during disease progression conferring a worse prognosis and can be potentially used as a biomarker of disease progression and therapeutic target, particularly in triple-negative and in ductal invasive carcinoma.
{"title":"ENO1 as a Biomarker of Breast Cancer Progression and Metastasis: A Bioinformatic Approach Using Available Databases.","authors":"Athina Giannoudis, Alistair Heath, Vijay Sharma","doi":"10.1177/11782234241285648","DOIUrl":"10.1177/11782234241285648","url":null,"abstract":"<p><strong>Background: </strong>Metabolic reprogramming is one of the hallmarks of cancer, and in breast cancer (BC), several metabolic enzymes are overexpressed and overactivated. One of these, Enolase 1 (ENO1), catalyses glycolysis and is involved in the regulation of multiple signalling pathways.</p><p><strong>Objectives: </strong>This study aimed to evaluate in silico the prognostic and predictive effects of ENO1 expression in BC.</p><p><strong>Design: </strong>This is a bioinformatic in silico analysis.</p><p><strong>Methods: </strong>Using available online platforms (Kaplan-Meier [KM] plotter, receiver operating characteristic curve [ROC] plotter, cBioPortal, Genotype-2-Outcome [G-2-O], MethSurv, and Tumour-Immune System Interaction Database [TISIDB]), we performed a bioinformatic in silico analysis to establish the prognostic and predictive effects related to ENO1 expression in BC. A network analysis was performed using the Oncomine platform, and signalling, epigenetic, and immune regulation pathways were explored.</p><p><strong>Results: </strong>ENO1 was overexpressed in all the analysed Oncomine, epigenetic, and immune pathways in triple-negative, but not in hormone receptor-positive BCs. In human epidermal growth factor receptor 2 (HER2)-positive BCs, ENO1 expression showed a mixed profile. Analysis on disease progression and histological types showed ENO1 overexpression in ductal in situ and invasive carcinoma, in high-grade tumours followed by advanced or metastasis and was linked to worse survival. High ENO1 expression was also associated with relapse-free, distant metastasis-free and overall survival, irrespectively of treatment and was mainly related to basal subtype.</p><p><strong>Conclusion: </strong>ENO1 overexpression recruits a range of signalling pathways during disease progression conferring a worse prognosis and can be potentially used as a biomarker of disease progression and therapeutic target, particularly in triple-negative and in ductal invasive carcinoma.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557172","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 : 2024-10-08eCollection Date: 2024-01-01DOI: 10.1177/11782234241282519
Rebecca Wilkinson, Lynn Smith
Background: Breast cancer diagnosis and treatment processes affect patients physically and mentally, and have an impact on their quality of life, even years after receiving treatment.
Objectives: The objective of this study was to determine the quality of life in female breast cancer patients and survivors in a South African context. The municipality within which participants were recruited for this study was Ekurhuleni, based in the Gauteng province, South Africa.
Design: This study followed a cross-sectional research design. Quantitative data was collected.
Methods: The Quality-of-Life Patient/Cancer Survivor Version (2012) was used to determine participants' quality of life in 4 subscales, namely, physical, psychological, social, and spiritual. The questionnaire was accessible to participants via the online Google Forms platform as well as in hard-copy format at local medical facilities. The Statistical Package for Social Sciences (SPSS) was used to compute statistics, and the level of significance was set at 95% (P < .05).
Results: One hundred female breast cancer patients and survivors from the region of Ekurhuleni, South Africa, took part in this study. The findings demonstrate that the quality-of-life subscale with the highest score was spiritual well-being (6.66 ± 2.07) and the lowest was psychological well-being (4.91 ± 1.93). No significant difference was found between quality of life and type of facility attended. Significant differences were found in quality-of-life ratings between breast cancer patient and breast cancer survivor populations.
Conclusion: Breast cancer can result in a compromised quality of life, and with the increased prevalence and survival rate of breast cancer patients, both the short- and long-term effects of the condition and its treatments are heightened.
{"title":"Quality of Life in Female Breast Cancer Patients and Survivors in a South African Municipality.","authors":"Rebecca Wilkinson, Lynn Smith","doi":"10.1177/11782234241282519","DOIUrl":"10.1177/11782234241282519","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer diagnosis and treatment processes affect patients physically and mentally, and have an impact on their quality of life, even years after receiving treatment.</p><p><strong>Objectives: </strong>The objective of this study was to determine the quality of life in female breast cancer patients and survivors in a South African context. The municipality within which participants were recruited for this study was Ekurhuleni, based in the Gauteng province, South Africa.</p><p><strong>Design: </strong>This study followed a cross-sectional research design. Quantitative data was collected.</p><p><strong>Methods: </strong>The Quality-of-Life Patient/Cancer Survivor Version (2012) was used to determine participants' quality of life in 4 subscales, namely, physical, psychological, social, and spiritual. The questionnaire was accessible to participants via the online Google Forms platform as well as in hard-copy format at local medical facilities. The Statistical Package for Social Sciences (SPSS) was used to compute statistics, and the level of significance was set at 95% (<i>P</i> < .05).</p><p><strong>Results: </strong>One hundred female breast cancer patients and survivors from the region of Ekurhuleni, South Africa, took part in this study. The findings demonstrate that the quality-of-life subscale with the highest score was spiritual well-being (6.66 ± 2.07) and the lowest was psychological well-being (4.91 ± 1.93). No significant difference was found between quality of life and type of facility attended. Significant differences were found in quality-of-life ratings between breast cancer patient and breast cancer survivor populations.</p><p><strong>Conclusion: </strong>Breast cancer can result in a compromised quality of life, and with the increased prevalence and survival rate of breast cancer patients, both the short- and long-term effects of the condition and its treatments are heightened.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399410","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}
Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by poor prognosis due to the absence of effective targeted therapies. Emerging evidence indicates that the gut microbiota and its metabolites play a key role in the occurrence and development of TNBC. This study aimed to explore the metabolic changes and potential mechanisms associated with TNBC.
Objectives: This study aimed to explore the potential relationship between targeted metabolites and the gut microbiota in TNBC.
Design: We recruited 8 participants, including 4 with TNBC and 4 with benign fibroadenomas as controls.
Methods: The gut microbiota was analyzed using metagenomics on fecal samples. Liquid chromatography-mass spectrometry (LC-MS) was employed to identify differential metabolites in serum and fecal samples. The correlation between the gut microbiota and metabolites was analyzed using Spearman's correlation analysis.
Results: Analysis of altered serum metabolites in the TNBC group revealed changes, particularly in carboxylic acids and derivatives, benzene, and substituted derivatives. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis revealed significant enrichment in 18 pathways. Regarding fecal metabolites, differences between the 2 groups also included carboxylic acids and derivatives, benzene, and substituted derivatives, with 28 metabolic pathways enriched based on KEGG pathway analysis. Metagenomics analysis showed differences in the relative abundance of Anaerococcus, Fischerella, and Schizosaccharomyces at the genus level, which have been previously associated with breast cancer. Furthermore, 4 serum metabolites-L-glutamine, citrate, creatinine, and creatine-along with 9 fecal metabolites, were associated with the aforementioned microbiota.
Conclusion: Our findings highlight distinct metabolite profiles in the serum and feces of patients with TNBC. The identification of gut microbiota and their associated metabolites provides new insights into the pathophysiological mechanisms underlying TNBC.
{"title":"Serum and Fecal Metabolite Profiles Linking With Gut Microbiome in Triple-Negative Breast Cancer Patients.","authors":"Jiawei Liu, Jing Shi, Tingting Zhang, Mie Chen, Zhennan Li, Cheng Lu, Fengliang Wang","doi":"10.1177/11782234241285645","DOIUrl":"10.1177/11782234241285645","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by poor prognosis due to the absence of effective targeted therapies. Emerging evidence indicates that the gut microbiota and its metabolites play a key role in the occurrence and development of TNBC. This study aimed to explore the metabolic changes and potential mechanisms associated with TNBC.</p><p><strong>Objectives: </strong>This study aimed to explore the potential relationship between targeted metabolites and the gut microbiota in TNBC.</p><p><strong>Design: </strong>We recruited 8 participants, including 4 with TNBC and 4 with benign fibroadenomas as controls.</p><p><strong>Methods: </strong>The gut microbiota was analyzed using metagenomics on fecal samples. Liquid chromatography-mass spectrometry (LC-MS) was employed to identify differential metabolites in serum and fecal samples. The correlation between the gut microbiota and metabolites was analyzed using Spearman's correlation analysis.</p><p><strong>Results: </strong>Analysis of altered serum metabolites in the TNBC group revealed changes, particularly in carboxylic acids and derivatives, benzene, and substituted derivatives. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis revealed significant enrichment in 18 pathways. Regarding fecal metabolites, differences between the 2 groups also included carboxylic acids and derivatives, benzene, and substituted derivatives, with 28 metabolic pathways enriched based on KEGG pathway analysis. Metagenomics analysis showed differences in the relative abundance of <i>Anaerococcus</i>, <i>Fischerella</i>, and <i>Schizosaccharomyces</i> at the genus level, which have been previously associated with breast cancer. Furthermore, 4 serum metabolites-L-glutamine, citrate, creatinine, and creatine-along with 9 fecal metabolites, were associated with the aforementioned microbiota.</p><p><strong>Conclusion: </strong>Our findings highlight distinct metabolite profiles in the serum and feces of patients with TNBC. The identification of gut microbiota and their associated metabolites provides new insights into the pathophysiological mechanisms underlying TNBC.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380009","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 : 2024-09-23eCollection Date: 2024-01-01DOI: 10.1177/11782234241273666
Pratibha Shrestha, Mei-Chin Hsieh, Tekeda Ferguson, Edward S Peters, Edward Trapido, Qingzhao Yu, Quyen D Chu, Xiao-Cheng Wu
Background: Studies in the United States are scarce that assess the survival differences between breast-conserving surgery plus radiation (Breast-Conserving Therapy; BCT) and mastectomy groups using population-based data while accounting for sociodemographic and clinical factors that affect the survival of women with early-stage breast cancer (ESBC).
Objective: To assess whether BCT provides superior long-term overall survival (OS) and breast cancer-specific survival (BCSS) compared with mastectomy in women with ESBC, while considering key factors that impact survival.
Design: Cohort study.
Methods: We analyzed data on women aged 20 years and older diagnosed with stage I-II breast cancer (BC) in 2004 who received either BCT or mastectomy. The data were collected by 5 state cancer registries through the Centers for Disease Control and Prevention-funded Patterns of Care study. Multivariable Cox proportional hazard models, accounting for sociodemographic and clinical factors, were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity analysis involved optimal caliper propensity score (PS) matching to address residual confounding.
Results: Of the 3495 women, 41.5% underwent mastectomy. The 10-year OS and BCSS were 82.7% and 91.1% for BCT and 72.3% and 85.7% for mastectomy, respectively. Adjusted models showed that mastectomy recipients had a 22% higher risk of all-cause deaths (ACD) (HR = 1.22, 95% CI = [1.06, 1.41]) and a 26% higher risk of breast cancer-specific deaths (BCD) (HR = 1.26, 95% CI = [1.02, 1.55]) than BCT recipients. Sensitivity analysis demonstrated that mastectomy was associated with a higher risk of ACD (P < .05) but did not exhibit a statistically significant risk for BCD. Women with HR+/HER2+ (luminal B) or invasive ductal carcinoma BC who underwent mastectomy had higher risks of ACD and BCD compared with BCT recipients, while the hazards for ACD in triple-negative BC did not remain significant after adjusting for covariates.
Conclusion: ESBC BCT recipients demonstrate superior OS and BCSS compared with mastectomy recipients.
{"title":"Higher 10-Year Survival with Breast-Conserving Therapy over Mastectomy for Women with Early-Stage (I-II) Breast Cancer: Analysis of the CDC Patterns of Care Data Base.","authors":"Pratibha Shrestha, Mei-Chin Hsieh, Tekeda Ferguson, Edward S Peters, Edward Trapido, Qingzhao Yu, Quyen D Chu, Xiao-Cheng Wu","doi":"10.1177/11782234241273666","DOIUrl":"https://doi.org/10.1177/11782234241273666","url":null,"abstract":"<p><strong>Background: </strong>Studies in the United States are scarce that assess the survival differences between breast-conserving surgery plus radiation (Breast-Conserving Therapy; BCT) and mastectomy groups using population-based data while accounting for sociodemographic and clinical factors that affect the survival of women with early-stage breast cancer (ESBC).</p><p><strong>Objective: </strong>To assess whether BCT provides superior long-term overall survival (OS) and breast cancer-specific survival (BCSS) compared with mastectomy in women with ESBC, while considering key factors that impact survival.</p><p><strong>Design: </strong>Cohort study.</p><p><strong>Methods: </strong>We analyzed data on women aged 20 years and older diagnosed with stage I-II breast cancer (BC) in 2004 who received either BCT or mastectomy. The data were collected by 5 state cancer registries through the Centers for Disease Control and Prevention-funded Patterns of Care study. Multivariable Cox proportional hazard models, accounting for sociodemographic and clinical factors, were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity analysis involved optimal caliper propensity score (PS) matching to address residual confounding.</p><p><strong>Results: </strong>Of the 3495 women, 41.5% underwent mastectomy. The 10-year OS and BCSS were 82.7% and 91.1% for BCT and 72.3% and 85.7% for mastectomy, respectively. Adjusted models showed that mastectomy recipients had a 22% higher risk of all-cause deaths (ACD) (HR = 1.22, 95% CI = [1.06, 1.41]) and a 26% higher risk of breast cancer-specific deaths (BCD) (HR = 1.26, 95% CI = [1.02, 1.55]) than BCT recipients. Sensitivity analysis demonstrated that mastectomy was associated with a higher risk of ACD (<i>P</i> < .05) but did not exhibit a statistically significant risk for BCD. Women with HR+/HER2+ (luminal B) or invasive ductal carcinoma BC who underwent mastectomy had higher risks of ACD and BCD compared with BCT recipients, while the hazards for ACD in triple-negative BC did not remain significant after adjusting for covariates.</p><p><strong>Conclusion: </strong>ESBC BCT recipients demonstrate superior OS and BCSS compared with mastectomy recipients.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341717","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 : 2024-09-06eCollection Date: 2024-01-01DOI: 10.1177/11782234241276310
Ali Khezrian, Ali Shojaeian, Armin Khaghani Boroujeni, Razieh Amini
As a heterogeneous disease, breast cancer (BC) has been characterized by the uncontrolled proliferation of mammary epithelial cells. The tumor microenvironment (TME) also contains inflammatory cells, fibroblasts, the extracellular matrix (ECM), and soluble factors that all promote BC progression. In this sense, the macrophage migration inhibitory factor (MIF), a pleiotropic pro-inflammatory cytokine and an upstream regulator of the immune response, enhances breast tumorigenesis through escalating cancer cell proliferation, survival, angiogenesis, invasion, metastasis, and stemness, which then brings tumorigenic effects by activating key oncogenic signaling pathways and inducing immunosuppression. Against this background, this review was to summarize the current understanding of the MIF pathogenic mechanisms in cancer, particularly BC, and address the central role of this immunoregulatory cytokine in signaling pathways and breast tumorigenesis. Furthermore, different inhibitors, such as small molecules as well as antibodies (Abs) or small interfering RNA (siRNA) and their anti-tumor effects in BC studies were examined. Small molecules and other therapy target MIF. Considering MIF as a promising therapeutic target, further clinical evaluation of MIF-targeted agents in patients with BC was warranted.
作为一种异质性疾病,乳腺癌(BC)的特点是乳腺上皮细胞不受控制的增殖。肿瘤微环境(TME)还包括炎症细胞、成纤维细胞、细胞外基质(ECM)和可溶性因子,它们都会促进乳腺癌的进展。从这个意义上说,巨噬细胞迁移抑制因子(MIF)是一种多向性促炎细胞因子,也是免疫反应的上游调节因子,它通过促进癌细胞增殖、存活、血管生成、侵袭、转移和干性,进而激活关键的致癌信号通路并诱导免疫抑制,从而增强乳腺肿瘤的发生。在此背景下,本综述旨在总结目前对 MIF 在癌症(尤其是 BC)中致病机制的认识,并探讨这种免疫调节细胞因子在信号通路和乳腺肿瘤发生中的核心作用。此外,还研究了不同的抑制剂,如小分子、抗体(Abs)或小干扰 RNA(siRNA)及其在 BC 研究中的抗肿瘤效果。以 MIF 为靶点的小分子和其他疗法。考虑到MIF是一个很有前景的治疗靶点,有必要对MIF靶向药物在BC患者中的应用进行进一步的临床评估。
{"title":"Therapeutic Opportunities in Breast Cancer by Targeting Macrophage Migration Inhibitory Factor as a Pleiotropic Cytokine.","authors":"Ali Khezrian, Ali Shojaeian, Armin Khaghani Boroujeni, Razieh Amini","doi":"10.1177/11782234241276310","DOIUrl":"10.1177/11782234241276310","url":null,"abstract":"<p><p>As a heterogeneous disease, breast cancer (BC) has been characterized by the uncontrolled proliferation of mammary epithelial cells. The tumor microenvironment (TME) also contains inflammatory cells, fibroblasts, the extracellular matrix (ECM), and soluble factors that all promote BC progression. In this sense, the macrophage migration inhibitory factor (MIF), a pleiotropic pro-inflammatory cytokine and an upstream regulator of the immune response, enhances breast tumorigenesis through escalating cancer cell proliferation, survival, angiogenesis, invasion, metastasis, and stemness, which then brings tumorigenic effects by activating key oncogenic signaling pathways and inducing immunosuppression. Against this background, this review was to summarize the current understanding of the MIF pathogenic mechanisms in cancer, particularly BC, and address the central role of this immunoregulatory cytokine in signaling pathways and breast tumorigenesis. Furthermore, different inhibitors, such as small molecules as well as antibodies (Abs) or small interfering RNA (siRNA) and their anti-tumor effects in BC studies were examined. Small molecules and other therapy target MIF. Considering MIF as a promising therapeutic target, further clinical evaluation of MIF-targeted agents in patients with BC was warranted.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153150","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 : 2024-08-24eCollection Date: 2024-01-01DOI: 10.1177/11782234241274683
Mary Mally, Novatus Tesha, Amani Anaeli
Background: Breast cancer is the leading cause of cancer-related death among women worldwide. Mortality from breast cancer can be reduced through early detection and prevention. Despite the availability of breast cancer screening methods, the uptake of screening services remains very low, especially in low-resource countries like Tanzania. This low uptake of screening services may be attributed to a lack of awareness regarding the importance of early detection of the disease.
Objectives: This study was set to determine breast cancer awareness and the uptake of breast cancer screening services among undergraduate female students in Dar es Salaam, Tanzania.
Design: The study was a descriptive cross-sectional study using the quantitative approach.
Methods: The sample size calculated for this study was 434 undergraduate female students. The tool used for data collection was self-administered questionnaires, with data collection taking place in July 2022. Data were analyzed using Stata Version 15 and presented using descriptive and inferential statistics.
Results: We found that most of the participants (92.38%) had heard about breast cancer, and only 39% of the participants were able to correctly identify the risk factors for breast cancer. Participants who had ever used breast cancer screening services by at least 1 method were 37 (9.23%), and the most common screening method practiced by the study participants was breast self-examination (48.65%).
Conclusions: Most of the participants were not aware of the screening methods for early detection of breast cancer. In addition, they lacked knowledge of some of the risk factors as evidenced by the low uptake of breast cancer screening services among the study participants. This calls for an awareness-raising campaign on the importance of breast cancer screening.
{"title":"Breast Cancer Awareness and Uptake of Breast Cancer Screening Services Among Undergraduate Female Students in the Oldest University of Tanzania: A Cross-Sectional Study.","authors":"Mary Mally, Novatus Tesha, Amani Anaeli","doi":"10.1177/11782234241274683","DOIUrl":"10.1177/11782234241274683","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the leading cause of cancer-related death among women worldwide. Mortality from breast cancer can be reduced through early detection and prevention. Despite the availability of breast cancer screening methods, the uptake of screening services remains very low, especially in low-resource countries like Tanzania. This low uptake of screening services may be attributed to a lack of awareness regarding the importance of early detection of the disease.</p><p><strong>Objectives: </strong>This study was set to determine breast cancer awareness and the uptake of breast cancer screening services among undergraduate female students in Dar es Salaam, Tanzania.</p><p><strong>Design: </strong>The study was a descriptive cross-sectional study using the quantitative approach.</p><p><strong>Methods: </strong>The sample size calculated for this study was 434 undergraduate female students. The tool used for data collection was self-administered questionnaires, with data collection taking place in July 2022. Data were analyzed using Stata Version 15 and presented using descriptive and inferential statistics.</p><p><strong>Results: </strong>We found that most of the participants (92.38%) had heard about breast cancer, and only 39% of the participants were able to correctly identify the risk factors for breast cancer. Participants who had ever used breast cancer screening services by at least 1 method were 37 (9.23%), and the most common screening method practiced by the study participants was breast self-examination (48.65%).</p><p><strong>Conclusions: </strong>Most of the participants were not aware of the screening methods for early detection of breast cancer. In addition, they lacked knowledge of some of the risk factors as evidenced by the low uptake of breast cancer screening services among the study participants. This calls for an awareness-raising campaign on the importance of breast cancer screening.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054925","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}
Approximately 10% to 15% of breast cancer cases in young women are diagnosed in patients harbouring germline (g) pathogenic or likely pathogenic variants (PVs) in the BReast CAncer 1 (BRCA1) or BReast CAncer 2 (BRCA2) genes. Preclinical and clinical studies showed a potential negative effect of germline BRCA1/2 (gBRCA1/2) PVs on ovarian reserve and reproductive potential, even before starting anticancer therapies. The aim of this article is to summarize the current literature on the fertility potential of young gBRCA1/2 PVs carriers with breast cancer and the risk of gonadotoxicity associated with anticancer treatments. Moreover, we describe the available evidence on the efficacy of fertility preservation techniques in young gBRCA1/2 PVs carriers and the safety data on having a pregnancy after breast cancer treatment.
{"title":"Fertility and Pregnancy-Related Issues in Young <i>BRCA</i> Carriers With Breast Cancer.","authors":"Isotta Martha Magaton, Luca Arecco, Elene Mariamidze, Kristina Jankovic, Mihaela Stana, Giulia Buzzatti, Lucia Trevisan, Graziana Scavone, Silvia Ottonello, Piero Fregatti, Claudia Massarotti, Michael von Wolff, Matteo Lambertini","doi":"10.1177/11782234241261429","DOIUrl":"10.1177/11782234241261429","url":null,"abstract":"<p><p>Approximately 10% to 15% of breast cancer cases in young women are diagnosed in patients harbouring germline (g) pathogenic or likely pathogenic variants (PVs) in the BReast CAncer 1 (<i>BRCA1</i>) or BReast CAncer 2 (<i>BRCA2</i>) genes. Preclinical and clinical studies showed a potential negative effect of germline <i>BRCA</i>1/2 (g<i>BRCA1/2</i>) PVs on ovarian reserve and reproductive potential, even before starting anticancer therapies. The aim of this article is to summarize the current literature on the fertility potential of young g<i>BRCA1/2</i> PVs carriers with breast cancer and the risk of gonadotoxicity associated with anticancer treatments. Moreover, we describe the available evidence on the efficacy of fertility preservation techniques in young g<i>BRCA1/2</i> PVs carriers and the safety data on having a pregnancy after breast cancer treatment.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330342","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}
Background: The application of sentinel lymph node biopsy (SLNB) has expanded from early breast cancer to locally advanced breast cancer with neoadjuvant chemotherapy (NAC). For patients with negative axillary lymph nodes, performing SLNB before or after NAC remains controversial.
Objectives: To evaluate the diagnostic feasibility and reliability of SLNB after NAC in breast cancer patients with negative axillary nodes at initial diagnosis.
Design: To calculate pooled identification rate (IR) and false negative rate (FNR) of SLNB after NAC on breast cancer patients with initially negative axillary nodes by enrolling relevant studies and perform subgroup analysis by the type of tracer and the number of biopsied sentinel lymph nodes in average.
Data sources and methods: The PubMed, Embase, Cochrane, Web of Science, and Scopus databases from January 1, 2002, to March 1, 2022, were searched for studies. The QUADAS-2 tool and MINORS item were employed to evaluate the quality of the included studies. I2 and Q tests were used to evaluate the heterogeneity among the studies. Random-effects model and fixed-effects model were employed to calculate the pooled IR, FNR, and 95% confidence interval (CI). Publication bias was evaluated, and sensitivity analysis was performed. Subgroup analysis was performed according to the type of tracer (single/double) and the number of biopsied sentinel lymph nodes in average (⩽2/>2).
Results: A total of 21 studies covering 1716 patients were enrolled in this study (IR = 93%, 95% CI = 90-96; FNR = 8%, 95% CI = 6-11).
Conclusion: The SLNB after NAC can serve as a feasible and reliable approach in breast cancer patients with negative axillary lymph node. In our study, no significant impact of tracer was found on the IR and FNR of SLNB, and the number of biopsy nodes >2 leads to the decreased FNR of SLNB.
背景:前哨淋巴结活检(SLNB)的应用已从早期乳腺癌扩展到接受新辅助化疗(NAC)的局部晚期乳腺癌。对于腋窝淋巴结阴性的患者,在新辅助化疗之前还是之后进行前哨淋巴结活检仍存在争议:评估对初诊时腋窝淋巴结阴性的乳腺癌患者在 NAC 后进行 SLNB 诊断的可行性和可靠性:设计:通过纳入相关研究,计算NAC后SLNB对初始腋窝结节阴性的乳腺癌患者的集合识别率(IR)和假阴性率(FNR),并根据示踪剂类型和活检前哨淋巴结的平均数量进行亚组分析:对2002年1月1日至2022年3月1日期间的PubMed、Embase、Cochrane、Web of Science和Scopus数据库进行了研究检索。采用QUADAS-2工具和MINORS项目来评估纳入研究的质量。采用 I2 和 Q 检验来评估研究之间的异质性。采用随机效应模型和固定效应模型计算汇总的IR、FNR和95%置信区间(CI)。评估了发表偏倚,并进行了敏感性分析。根据示踪剂的类型(单/双)和活检前哨淋巴结的平均数量(⩽2/>2)进行亚组分析:本研究共纳入21项研究,覆盖1716名患者(IR = 93%,95% CI = 90-96;FNR = 8%,95% CI = 6-11):结论:对于腋窝淋巴结阴性的乳腺癌患者,在 NAC 后进行 SLNB 是一种可行且可靠的方法。我们的研究发现,示踪剂对SLNB的IR和FNR无明显影响,活检结节数大于2会导致SLNB的FNR下降。
{"title":"The Feasibility and Reliability of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Breast Cancer Patients With Negative Axillary Lymph Nodes-A Meta-analysis.","authors":"Mengjie Yu, Yu Liu, Zenan Huang, Qingqing Zhu, Yong Huang","doi":"10.1177/11782234241255856","DOIUrl":"10.1177/11782234241255856","url":null,"abstract":"<p><strong>Background: </strong>The application of sentinel lymph node biopsy (SLNB) has expanded from early breast cancer to locally advanced breast cancer with neoadjuvant chemotherapy (NAC). For patients with negative axillary lymph nodes, performing SLNB before or after NAC remains controversial.</p><p><strong>Objectives: </strong>To evaluate the diagnostic feasibility and reliability of SLNB after NAC in breast cancer patients with negative axillary nodes at initial diagnosis.</p><p><strong>Design: </strong>To calculate pooled identification rate (IR) and false negative rate (FNR) of SLNB after NAC on breast cancer patients with initially negative axillary nodes by enrolling relevant studies and perform subgroup analysis by the type of tracer and the number of biopsied sentinel lymph nodes in average.</p><p><strong>Data sources and methods: </strong>The PubMed, Embase, Cochrane, Web of Science, and Scopus databases from January 1, 2002, to March 1, 2022, were searched for studies. The QUADAS-2 tool and MINORS item were employed to evaluate the quality of the included studies. <i>I</i><sup>2</sup> and Q tests were used to evaluate the heterogeneity among the studies. Random-effects model and fixed-effects model were employed to calculate the pooled IR, FNR, and 95% confidence interval (CI). Publication bias was evaluated, and sensitivity analysis was performed. Subgroup analysis was performed according to the type of tracer (single/double) and the number of biopsied sentinel lymph nodes in average (⩽2/>2).</p><p><strong>Results: </strong>A total of 21 studies covering 1716 patients were enrolled in this study (IR = 93%, 95% CI = 90-96; FNR = 8%, 95% CI = 6-11).</p><p><strong>Conclusion: </strong>The SLNB after NAC can serve as a feasible and reliable approach in breast cancer patients with negative axillary lymph node. In our study, no significant impact of tracer was found on the IR and FNR of SLNB, and the number of biopsy nodes >2 leads to the decreased FNR of SLNB.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199428","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 : 2024-05-20eCollection Date: 2024-01-01DOI: 10.1177/11782234241255211
Mehwish Mooghal, Muhammad Ali Akbar Khan, Mirza Rameez Samar, Hafsa Shaikh, Azmina Tajdin Valimohammad, Romana Idrees, Yasmin Abdul Rashid, Abida K Sattar
Background: Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, node-negative, or 1 to 3 lymph node-positive early breast cancers (EBCs). The cost of the test, which is not available in low-middle income countries (LMICs), is not within the means of most individuals. The Ki-67 index is a marker of tumor proliferation that is cost-effective and easily performed and has been substituted in many cases to obtain prognostic information.
Objective: We aimed to identify the correlation between the ODx recurrence score (RS) and the Ki-67 index in HR-positive EBCs and to determine whether Ki-67, like the ODx, can help facilitate clinical decision-making.
Design: Systematic review correlating Ki-67 index and ODx in HR-positive and HER2-negative EBCs as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Data sources and methods: We searched different databases between January 2010 and May 2023 and included retrospective/prospective cohorts, clinical trials, case-control, and cross-sectional studies involving HR-positive and HER2-negative EBCs correlating the Ki-67 index and ODx RS categories.
Results: Of the 18 studies included, 16 indicated a positive or weakly positive correlation between ODx and the Ki-67 index. The combined P value of the included studies is <0.05 (P = .000), which shows a statistical significance between the 2. Our review also discusses the potential of machine learning and artificial intelligence (AI) in Ki-67 assessment, offering a cost-effective and reproducible alternative.
Conclusion: Even although there are limitations, studies indicate a favorable association between ODx and the Ki-67 index in specific situations. This implies that Ki-67 can offer important predictive details, especially regarding the likelihood of relapse in HR-positive EBC. This is particularly significant in LMICs where financial constraints often hinder the availability of costly diagnostic tests.
{"title":"Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature.","authors":"Mehwish Mooghal, Muhammad Ali Akbar Khan, Mirza Rameez Samar, Hafsa Shaikh, Azmina Tajdin Valimohammad, Romana Idrees, Yasmin Abdul Rashid, Abida K Sattar","doi":"10.1177/11782234241255211","DOIUrl":"10.1177/11782234241255211","url":null,"abstract":"<p><strong>Background: </strong>Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, node-negative, or 1 to 3 lymph node-positive early breast cancers (EBCs). The cost of the test, which is not available in low-middle income countries (LMICs), is not within the means of most individuals. The Ki-67 index is a marker of tumor proliferation that is cost-effective and easily performed and has been substituted in many cases to obtain prognostic information.</p><p><strong>Objective: </strong>We aimed to identify the correlation between the ODx recurrence score (RS) and the Ki-67 index in HR-positive EBCs and to determine whether Ki-67, like the ODx, can help facilitate clinical decision-making.</p><p><strong>Design: </strong>Systematic review correlating Ki-67 index and ODx in HR-positive and HER2-negative EBCs as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.</p><p><strong>Data sources and methods: </strong>We searched different databases between January 2010 and May 2023 and included retrospective/prospective cohorts, clinical trials, case-control, and cross-sectional studies involving HR-positive and HER2-negative EBCs correlating the Ki-67 index and ODx RS categories.</p><p><strong>Results: </strong>Of the 18 studies included, 16 indicated a positive or weakly positive correlation between ODx and the Ki-67 index. The combined <i>P</i> value of the included studies is <0.05 (<i>P</i> = .000), which shows a statistical significance between the 2. Our review also discusses the potential of machine learning and artificial intelligence (AI) in Ki-67 assessment, offering a cost-effective and reproducible alternative.</p><p><strong>Conclusion: </strong>Even although there are limitations, studies indicate a favorable association between ODx and the Ki-67 index in specific situations. This implies that Ki-67 can offer important predictive details, especially regarding the likelihood of relapse in HR-positive EBC. This is particularly significant in LMICs where financial constraints often hinder the availability of costly diagnostic tests.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080656","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}