Pub Date : 2024-09-18eCollection Date: 2024-01-01DOI: 10.2147/BCTT.S478328
Xin Yang, Lei Fan, Jicheng Huang, Yongjun Li
Background: Timely detection of tumor progression in breast cancer (BC) patients is critical for therapeutic management and prognosis. Plasma exosomal miRNAs are potential liquid biopsy markers for monitoring tumor progression, but their roles in BC remain unclear.
Methods: In the TCGA database, we first screened for miRNAs significantly associated with BC progression by comparing miRNA expression in para-carcinoma tissues, stage I BC tissues, and stage II-III BC tissues (n = 1026). Cox regression analyses and survival analyses were performed on candidate miRNAs to explore their prognostic value (n = 848). KEGG, GO, and PPI analyses were used to identify enriched pathways associated with cancer. Finally, the potential of candidate miRNAs as liquid biopsy markers was evaluated by sequencing and analyzing plasma exosomal miRNAs from our collection of 45 BC patients (14 in stage I, 31 in stage II-III) and 5 healthy controls, combined with qRT-PCR analysis to assess the correlation of candidate gene expression in plasma exosomes and BC tissues.
Results: We found that only miR-203a-3p was progressively elevated with BC progression and was associated with poor prognosis in the TCGA dataset. Its potential target genes were enriched in pathways related to tumor progression, and the downregulation of 48 of these genes was associated with poor prognosis. More importantly, plasma exosomal miR-203a-3p was also found to gradually increase with BC progression, and its expression was positively correlated with miR-203a-3p in BC tissues. This result suggests that plasma exosomal miR-203a-3p may reflect the expression of miR-203a-3p in tumor tissues and serve as a potential liquid biopsy marker for monitoring BC progressions.
Conclusion: We found for the first time that elevated miR-203a-3p was associated with BC progression and poor prognosis. Our findings suggested that plasma exosomal miR-203a-3p could hold potential as a liquid biopsy marker for evaluating BC progression in patients.
背景:及时检测乳腺癌(BC)患者的肿瘤进展对治疗管理和预后至关重要。血浆外泌体 miRNA 是监测肿瘤进展的潜在液体活检标记物,但它们在 BC 中的作用仍不清楚:在TCGA数据库中,我们首先通过比较癌旁组织、I期BC组织和II-III期BC组织(n = 1026)中的miRNA表达,筛选出与BC进展显著相关的miRNA。对候选 miRNA 进行了 Cox 回归分析和生存分析,以探讨其预后价值(n = 848)。KEGG、GO和PPI分析用于确定与癌症相关的富集通路。最后,通过对我们收集的 45 例 BC 患者(14 例 I 期,31 例 II-III 期)和 5 例健康对照的血浆外泌体 miRNA 进行测序和分析,结合 qRT-PCR 分析评估血浆外泌体和 BC 组织中候选基因表达的相关性,从而评估候选 miRNA 作为液体活检标志物的潜力:结果:我们发现,在TCGA数据集中,只有miR-203a-3p随着BC的进展而逐渐升高,并与不良预后相关。miR-203a-3p的潜在靶基因富集在与肿瘤进展相关的通路中,其中48个基因的下调与预后不良有关。更重要的是,研究还发现血浆外泌体 miR-203a-3p 会随着 BC 的进展而逐渐增加,其表达量与 BC 组织中的 miR-203a-3p 呈正相关。这一结果表明,血浆外泌体miR-203a-3p可能反映了肿瘤组织中miR-203a-3p的表达,可作为监测BC进展的潜在液体活检标志物:我们首次发现,miR-203a-3p 的升高与 BC 病程进展和预后不良有关。我们的研究结果表明,血浆外泌体miR-203a-3p有可能成为一种液体活检标志物,用于评估BC患者的病情进展。
{"title":"Plasma Exosome miR-203a-3p is a Potential Liquid Biopsy Marker for Assessing Tumor Progression in Breast Cancer Patients.","authors":"Xin Yang, Lei Fan, Jicheng Huang, Yongjun Li","doi":"10.2147/BCTT.S478328","DOIUrl":"10.2147/BCTT.S478328","url":null,"abstract":"<p><strong>Background: </strong>Timely detection of tumor progression in breast cancer (BC) patients is critical for therapeutic management and prognosis. Plasma exosomal miRNAs are potential liquid biopsy markers for monitoring tumor progression, but their roles in BC remain unclear.</p><p><strong>Methods: </strong>In the TCGA database, we first screened for miRNAs significantly associated with BC progression by comparing miRNA expression in para-carcinoma tissues, stage I BC tissues, and stage II-III BC tissues (n = 1026). Cox regression analyses and survival analyses were performed on candidate miRNAs to explore their prognostic value (n = 848). KEGG, GO, and PPI analyses were used to identify enriched pathways associated with cancer. Finally, the potential of candidate miRNAs as liquid biopsy markers was evaluated by sequencing and analyzing plasma exosomal miRNAs from our collection of 45 BC patients (14 in stage I, 31 in stage II-III) and 5 healthy controls, combined with qRT-PCR analysis to assess the correlation of candidate gene expression in plasma exosomes and BC tissues.</p><p><strong>Results: </strong>We found that only miR-203a-3p was progressively elevated with BC progression and was associated with poor prognosis in the TCGA dataset. Its potential target genes were enriched in pathways related to tumor progression, and the downregulation of 48 of these genes was associated with poor prognosis. More importantly, plasma exosomal miR-203a-3p was also found to gradually increase with BC progression, and its expression was positively correlated with miR-203a-3p in BC tissues. This result suggests that plasma exosomal miR-203a-3p may reflect the expression of miR-203a-3p in tumor tissues and serve as a potential liquid biopsy marker for monitoring BC progressions.</p><p><strong>Conclusion: </strong>We found for the first time that elevated miR-203a-3p was associated with BC progression and poor prognosis. Our findings suggested that plasma exosomal miR-203a-3p could hold potential as a liquid biopsy marker for evaluating BC progression in patients.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17eCollection Date: 2024-01-01DOI: 10.2147/BCTT.S480796
Xiaojuan Gao, Tiansheng Bu, Wenying Wang, Ying Xu
Breast cancer remains the most prevalent malignancy among women globally, presenting significant challenges in therapeutic strategies due to tumor heterogeneity, drug resistance, and adverse side effects. Recent advances in targeted therapies, particularly antibody-drug conjugates (ADCs), have shown promise in addressing these challenges by selectively targeting tumor cells while sparing normal tissues. This study provides a comprehensive analysis of two innovative ADCs targeting HER2 and Trop-2, which are critical markers in various breast cancer subtypes. These conjugates combine potent cytotoxic drugs with specific antibodies, leveraging the antigens' differential expression to enhance therapeutic efficacy and reduce systemic toxicity. Our comparative analysis highlights the clinical applications, efficacy, and safety profiles of these ADCs, drawing on data from recent clinical trials. In addition, the paper discusses the potential of these ADCs in treating other types of cancers where HER2 and Trop-2 are expressed, as well as the toxicity risks associated with targeting these antigens in normal cells. Additionally, the paper discusses novel synthetic drugs that show potential in preclinical models, focusing on their mechanisms of action and therapeutic advantages over traditional chemotherapy. The findings underscore the transformative impact of targeted ADCs in breast cancer treatment, noting significant advancements in patient outcomes and management of side effects. However, ongoing issues such as resistance mechanisms and long-term safety remain challenges. The conclusion offers a forward-looking perspective on potential improvements and the future trajectory of ADC research. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics, with particular attention to their broader applications and associated risks.
{"title":"Comparative Analysis and Future Prospects of Human Epidermal Growth Factor Receptor 2 (HER2) and Trophoblast Cell-Surface Antigen 2 (Trop-2) Targeted Antibody-Drug Conjugates in Breast Cancer Treatment.","authors":"Xiaojuan Gao, Tiansheng Bu, Wenying Wang, Ying Xu","doi":"10.2147/BCTT.S480796","DOIUrl":"10.2147/BCTT.S480796","url":null,"abstract":"<p><p>Breast cancer remains the most prevalent malignancy among women globally, presenting significant challenges in therapeutic strategies due to tumor heterogeneity, drug resistance, and adverse side effects. Recent advances in targeted therapies, particularly antibody-drug conjugates (ADCs), have shown promise in addressing these challenges by selectively targeting tumor cells while sparing normal tissues. This study provides a comprehensive analysis of two innovative ADCs targeting HER2 and Trop-2, which are critical markers in various breast cancer subtypes. These conjugates combine potent cytotoxic drugs with specific antibodies, leveraging the antigens' differential expression to enhance therapeutic efficacy and reduce systemic toxicity. Our comparative analysis highlights the clinical applications, efficacy, and safety profiles of these ADCs, drawing on data from recent clinical trials. In addition, the paper discusses the potential of these ADCs in treating other types of cancers where HER2 and Trop-2 are expressed, as well as the toxicity risks associated with targeting these antigens in normal cells. Additionally, the paper discusses novel synthetic drugs that show potential in preclinical models, focusing on their mechanisms of action and therapeutic advantages over traditional chemotherapy. The findings underscore the transformative impact of targeted ADCs in breast cancer treatment, noting significant advancements in patient outcomes and management of side effects. However, ongoing issues such as resistance mechanisms and long-term safety remain challenges. The conclusion offers a forward-looking perspective on potential improvements and the future trajectory of ADC research. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics, with particular attention to their broader applications and associated risks.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16eCollection Date: 2024-01-01DOI: 10.2147/BCTT.S470417
Mariangela Boccardi, Savino Cilla, Mara Fanelli, Carmela Romano, Paolo Bonome, Milena Ferro, Donato Pezzulla, Roberto Di Marco, Francesco Deodato, Gabriella Macchia
Purpose: The most prevalent treatment-related side effect related to adjuvant radiotherapy (RT) for breast cancer is acute skin toxicity in the irradiated area. The purpose of this single-institution pilot study is to provide preliminary clinical results on the feasibility and safety of a breast ultra-hypofractionated radiation treatment delivered using an automated hybrid-VMAT technique. Skin damage was assessed both with clinical examination and objectively using a Cutometer equipment.
Patients and methods: Patients received 26 Gy to the whole breast and 30 Gy to the tumoral bed in 5 fractions using an automated hybrid-VMAT approach with the option for the breath hold technique if necessary. Acute and late toxicities were clinically evaluated at baseline, 1- and 6-months after treatment using the CTC-AE v.5.0 scale. An instrumental evaluation of the skin elasticity was performed using a Cutometer® Dual MP580. Two parameters per patient, R0 (the total skin firmness) and Q1 (the elastic recovery), were registered at the different timelines.
Results: From June 2022 to January 2024, 30 patients, stage T1-T2, N0 were enrolled in the study. Four out of 30 (13.3%) patients reported G2 acute skin toxicities. At 6 months, G2 late toxicity was registered in 3 patients (10%). A total of 2160 measures of R0 and Q1 were recorded. At 1 month after treatment, no correlation was found between measured values of R0 and Q1 and clinical evaluation. At 6 months after treatment, clinical late toxicity ≥1 was strongly associated with decreased R0 and Q1 values ≥24% (p = 0.003) and ≥18% (p = 0.022), respectively.
Conclusion: Ultra-hypofractionated whole-breast radiotherapy, when supported by advanced treatment techniques, is both feasible and safe. No severe adverse effects were observed at any of the different timeframes. Acute and late skin toxicities were shown to be lower in contrast to data presented in the literature.
{"title":"Ultra-Hypofractionated Whole Breast Radiotherapy with Automated Hybrid-VMAT Technique: A Pilot Study on Safety, Skin Toxicity and Aesthetic Outcomes.","authors":"Mariangela Boccardi, Savino Cilla, Mara Fanelli, Carmela Romano, Paolo Bonome, Milena Ferro, Donato Pezzulla, Roberto Di Marco, Francesco Deodato, Gabriella Macchia","doi":"10.2147/BCTT.S470417","DOIUrl":"10.2147/BCTT.S470417","url":null,"abstract":"<p><strong>Purpose: </strong>The most prevalent treatment-related side effect related to adjuvant radiotherapy (RT) for breast cancer is acute skin toxicity in the irradiated area. The purpose of this single-institution pilot study is to provide preliminary clinical results on the feasibility and safety of a breast ultra-hypofractionated radiation treatment delivered using an automated hybrid-VMAT technique. Skin damage was assessed both with clinical examination and objectively using a Cutometer equipment.</p><p><strong>Patients and methods: </strong>Patients received 26 Gy to the whole breast and 30 Gy to the tumoral bed in 5 fractions using an automated hybrid-VMAT approach with the option for the breath hold technique if necessary. Acute and late toxicities were clinically evaluated at baseline, 1- and 6-months after treatment using the CTC-AE v.5.0 scale. An instrumental evaluation of the skin elasticity was performed using a Cutometer<sup>®</sup> Dual MP580. Two parameters per patient, R0 (the total skin firmness) and Q1 (the elastic recovery), were registered at the different timelines.</p><p><strong>Results: </strong>From June 2022 to January 2024, 30 patients, stage T1-T2, N0 were enrolled in the study. Four out of 30 (13.3%) patients reported G2 acute skin toxicities. At 6 months, G2 late toxicity was registered in 3 patients (10%). A total of 2160 measures of R0 and Q1 were recorded. At 1 month after treatment, no correlation was found between measured values of R0 and Q1 and clinical evaluation. At 6 months after treatment, clinical late toxicity ≥1 was strongly associated with decreased R0 and Q1 values ≥24% (p = 0.003) and ≥18% (p = 0.022), respectively.</p><p><strong>Conclusion: </strong>Ultra-hypofractionated whole-breast radiotherapy, when supported by advanced treatment techniques, is both feasible and safe. No severe adverse effects were observed at any of the different timeframes. Acute and late skin toxicities were shown to be lower in contrast to data presented in the literature.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12eCollection Date: 2024-01-01DOI: 10.2147/BCTT.S473920
Fan Li, Chuan-Guo Chen, Jiao-Fei Wei, Jia-Wen Lin, Zi-Ang Dou, Jun Shen, Shu-Qin Li
Objective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR).
Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan-Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes.
Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06-6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66-3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR.
Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.
{"title":"Elevated Risk of Adverse Prognosis in Patients with T2-3 Stage Breast Cancer Exhibiting Non-Pathological Complete Response Following Neoadjuvant Chemotherapy: Significance of Regenerating Islet-Derived Family Member 4.","authors":"Fan Li, Chuan-Guo Chen, Jiao-Fei Wei, Jia-Wen Lin, Zi-Ang Dou, Jun Shen, Shu-Qin Li","doi":"10.2147/BCTT.S473920","DOIUrl":"https://doi.org/10.2147/BCTT.S473920","url":null,"abstract":"<p><strong>Objective: </strong>In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR).</p><p><strong>Methods: </strong>A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan-Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes.</p><p><strong>Results: </strong>The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06-6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66-3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR.</p><p><strong>Conclusion: </strong>Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09eCollection Date: 2024-01-01DOI: 10.2147/BCTT.S476083
Ruixi Li, Lulu Liu, Yong Liu, Jiang Tang, Jinsong Li
Introduction: Protocadherin 9 (PCDH9), a member of the cadherin superfamily of transmembrane proteins, plays a role in cell adhesion and neural development. Recent studies suggest that PCDH9 may function as a tumor suppressor in certain cancers, though its specific role in breast cancer remains unclear.
Methods: UALCAN database to retrieve information on PCDH9 expression in breast cancer tissues compared with that in normal tissues. The biological effects of PCDH9 in breast cancer cells were analyzed using the DepMap database. Stable knockdown or overexpression of PCDH9 in breast cancer cell lines and subsequently assessed tumor cell proliferation and migration. Synthetic lethal screening was conducted for breast cancer cells with low PCDH9 expression or deficiency.
Results: In this study, we observed significant downregulation of PCDH9 in breast cancer tissues, with its expression negatively correlated with progression-free survival. Further investigations revealed that decreased PCDH9 expression promotes breast cancer cell proliferation and migration, while overexpression of PCDH9 has the opposite effect. Subsequently, we identified the TAS-102, an approved drug for metastatic colorectal cancer, exhibited selective cytotoxicity against breast cancer cells with low PCDH9 expression.
Conclusion and discussion: In summary, our study identified PCDH9 as a tumor suppressor in breast cancer and highlighted TAS-102 as a potential therapeutic option for tumors with low PCDH9 expression or deficiency. The specific interaction between TAS-102 and PCDH9 warrants further exploration, providing deeper insights into its mode of action in treating PCDH9-deficient breast cancer.
{"title":"Unraveling the Role of PCDH9 in Breast Cancer and Identifying Therapeutic Strategies for PCDH9-Deficient Tumors.","authors":"Ruixi Li, Lulu Liu, Yong Liu, Jiang Tang, Jinsong Li","doi":"10.2147/BCTT.S476083","DOIUrl":"https://doi.org/10.2147/BCTT.S476083","url":null,"abstract":"<p><strong>Introduction: </strong>Protocadherin 9 (PCDH9), a member of the cadherin superfamily of transmembrane proteins, plays a role in cell adhesion and neural development. Recent studies suggest that PCDH9 may function as a tumor suppressor in certain cancers, though its specific role in breast cancer remains unclear.</p><p><strong>Methods: </strong>UALCAN database to retrieve information on PCDH9 expression in breast cancer tissues compared with that in normal tissues. The biological effects of PCDH9 in breast cancer cells were analyzed using the DepMap database. Stable knockdown or overexpression of PCDH9 in breast cancer cell lines and subsequently assessed tumor cell proliferation and migration. Synthetic lethal screening was conducted for breast cancer cells with low PCDH9 expression or deficiency.</p><p><strong>Results: </strong>In this study, we observed significant downregulation of PCDH9 in breast cancer tissues, with its expression negatively correlated with progression-free survival. Further investigations revealed that decreased PCDH9 expression promotes breast cancer cell proliferation and migration, while overexpression of PCDH9 has the opposite effect. Subsequently, we identified the TAS-102, an approved drug for metastatic colorectal cancer, exhibited selective cytotoxicity against breast cancer cells with low PCDH9 expression.</p><p><strong>Conclusion and discussion: </strong>In summary, our study identified PCDH9 as a tumor suppressor in breast cancer and highlighted TAS-102 as a potential therapeutic option for tumors with low PCDH9 expression or deficiency. The specific interaction between TAS-102 and PCDH9 warrants further exploration, providing deeper insights into its mode of action in treating PCDH9-deficient breast cancer.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11401061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05eCollection Date: 2024-01-01DOI: 10.2147/BCTT.S463024
Shaimaa G Ghazy, Mostafa A Abdel-Maksoud, Ibrahim A Saleh, Mohamed A El-Tayeb, Amr A Elsaid, Metwally A Kotb, Diana A Al-Sherif, Heba S Ramadan, Ahmed Elwahsh, Ahmed M Hussein, Ahmad S Kodous
Purpose: The local management approach for node-positive breast cancer has undergone substantial evolution. Consequently, there exists a pressing need to enhance our treatment strategies by placing greater emphasis on planning and dosimetric factors, given the availability of more conformal techniques and delineation criteria, achieving optimal goals of radiotherapy treatment. The primary aim of this article is to discuss how the extent of regional nodal coverage influences the choice between IMRT and 3D radiation therapy for patients.
Patients and methods: A total of 15 patients diagnosed with left breast cancer with disease involved lymph nodes were included in this study. Delivering the recommended dose required the use of a linear accelerator (LINAC) with photon beams energy of 6 mega voltage (6MV). Each patient had full breast radiation using two planning procedures: intensity-modulated radiotherapy (IMRT) and three-dimensional radiotherapy (3D conformal). Following the guidelines set forth by the Radiation Therapy Oncology Group (RTOG), the planned treatment coverage was carefully designed to fall between 95% and 107% of the recommended dose. Additionally, Dose Volume Histograms (DVHs) were generated the dose distribution within these anatomical contours.
Results and conclusion: The DVH parameters were subjected to a comparative analysis, focusing on the doses absorbed by both Organs at Risk (OARs) and the Planning Target Volume (PTV). The findings suggest that low doses in IMRT plan might raise the risk of adverse oncological outcomes or potentially result in an increased incidence of subsequent malignancies. Consequently, the adoption of inverse IMRT remains limited, and the decision to opt for this therapy should be reserved for situations where it is genuinely necessary to uphold a satisfactory quality of life. Additionally, this approach helps in reducing the likelihood of developing thyroid problems and mitigates the risk of injuries to the supraclavicular area and the proximal head of the humerus bone.
{"title":"Comparative Analysis of Dosimetry: IMRT versus 3DCRT in Left-Sided Breast Cancer Patients with Considering Some Organs in Out - of - Field Borders.","authors":"Shaimaa G Ghazy, Mostafa A Abdel-Maksoud, Ibrahim A Saleh, Mohamed A El-Tayeb, Amr A Elsaid, Metwally A Kotb, Diana A Al-Sherif, Heba S Ramadan, Ahmed Elwahsh, Ahmed M Hussein, Ahmad S Kodous","doi":"10.2147/BCTT.S463024","DOIUrl":"https://doi.org/10.2147/BCTT.S463024","url":null,"abstract":"<p><strong>Purpose: </strong>The local management approach for node-positive breast cancer has undergone substantial evolution. Consequently, there exists a pressing need to enhance our treatment strategies by placing greater emphasis on planning and dosimetric factors, given the availability of more conformal techniques and delineation criteria, achieving optimal goals of radiotherapy treatment. The primary aim of this article is to discuss how the extent of regional nodal coverage influences the choice between IMRT and 3D radiation therapy for patients.</p><p><strong>Patients and methods: </strong>A total of 15 patients diagnosed with left breast cancer with disease involved lymph nodes were included in this study. Delivering the recommended dose required the use of a linear accelerator (LINAC) with photon beams energy of 6 mega voltage (6MV). Each patient had full breast radiation using two planning procedures: intensity-modulated radiotherapy (IMRT) and three-dimensional radiotherapy (3D conformal). Following the guidelines set forth by the Radiation Therapy Oncology Group (RTOG), the planned treatment coverage was carefully designed to fall between 95% and 107% of the recommended dose. Additionally, Dose Volume Histograms (DVHs) were generated the dose distribution within these anatomical contours.</p><p><strong>Results and conclusion: </strong>The DVH parameters were subjected to a comparative analysis, focusing on the doses absorbed by both Organs at Risk (OARs) and the Planning Target Volume (PTV). The findings suggest that low doses in IMRT plan might raise the risk of adverse oncological outcomes or potentially result in an increased incidence of subsequent malignancies. Consequently, the adoption of inverse IMRT remains limited, and the decision to opt for this therapy should be reserved for situations where it is genuinely necessary to uphold a satisfactory quality of life. Additionally, this approach helps in reducing the likelihood of developing thyroid problems and mitigates the risk of injuries to the supraclavicular area and the proximal head of the humerus bone.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Marine algae are increasingly becoming a potential resource for new drugs. In recent decades, including Bornetella nitida (B. nitida). Meanwhile, antimicrobial and anticancer agents are the first line of choice for developing alternative compounds, considering the annually increasing resistant events. Therefore, this study aimed to examine the antimicrobial and cytotoxic potential of B. nitida isolate compounds.
Methods: The B. nitida resulted in 2 compounds, sitosterol 3β tetracosanoate and (E)-17-(8-ethyl-4,5,9-trimethyldec-6-en-2-yl)-13-methyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol. Both compounds were tested to have antibacterial effects against Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Methicillin-resistant Staphylococcus Aureus (MRSA). Proliferation assay was conducted using the PrestoBlue™ Cell Viability Reagent, which was also used to measure the IC50 against MCF-7 breast cancer cells.
Results: The results showed that (E)-17-(8-ethyl-4,5,9-trimethyldec-6-en-2-yl)-13-methyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol had antimicrobial activity against Staphylococcus aureus and IC50 value of 142.18 µg/mL against MCF-7 cells, while sitosterol 3β tetracosanoate does not have any antimicrobial activity and IC50 value of 681.65 µg/mL. Moreover, the mechanism prediction using docking with caspase-3 receptor to induce apoptosis was also evaluated.
Conclusion: Based on the results, (E)-17-(8-ethyl-4,5,9-trimethyldec-6-en-2-yl)-13-methyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol of B. nitida has great potential as an antimicrobial and anticancer agent.
{"title":"Antimicrobial and Cytotoxic Effect of <i>Bornetella Nitida</i> Green Algae Isolate on MCF-7 Breast Cancer.","authors":"Yuni Elsa Hadisaputri, Nunuk Hariani Soekamto, Pratiwi Pudjiastuti, Aria Aristokrat, Bahrun Bahrun, Fajar Fauzi Abdullah, Tatsufumi Okino","doi":"10.2147/BCTT.S469036","DOIUrl":"10.2147/BCTT.S469036","url":null,"abstract":"<p><strong>Introduction: </strong>Marine algae are increasingly becoming a potential resource for new drugs. In recent decades, including <i>Bornetella nitida</i> (<i>B. nitida</i>). Meanwhile, antimicrobial and anticancer agents are the first line of choice for developing alternative compounds, considering the annually increasing resistant events. Therefore, this study aimed to examine the antimicrobial and cytotoxic potential of <i>B. nitida</i> isolate compounds.</p><p><strong>Methods: </strong>The <i>B. nitida</i> resulted in 2 compounds, sitosterol 3β tetracosanoate and (E)-17-(8-ethyl-4,5,9-trimethyldec-6-en-2-yl)-13-methyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol. Both compounds were tested to have antibacterial effects against <i>Pseudomonas aeruginosa</i>, <i>Bacillus subtilis</i>, <i>Staphylococcus aureus</i>, <i>Methicillin-resistant Staphylococcus Aureus</i> (MRSA). Proliferation assay was conducted using the PrestoBlue™ Cell Viability Reagent, which was also used to measure the IC<sub>50</sub> against MCF-7 breast cancer cells.</p><p><strong>Results: </strong>The results showed that (E)-17-(8-ethyl-4,5,9-trimethyldec-6-en-2-yl)-13-methyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol had antimicrobial activity against <i>Staphylococcus aureus</i> and IC<sub>50</sub> value of 142.18 µg/mL against MCF-7 cells, while sitosterol 3β tetracosanoate does not have any antimicrobial activity and IC<sub>50</sub> value of 681.65 µg/mL. Moreover, the mechanism prediction using docking with caspase-3 receptor to induce apoptosis was also evaluated.</p><p><strong>Conclusion: </strong>Based on the results, (E)-17-(8-ethyl-4,5,9-trimethyldec-6-en-2-yl)-13-methyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol of <i>B. nitida</i> has great potential as an antimicrobial and anticancer agent.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02eCollection Date: 2024-01-01DOI: 10.2147/BCTT.S463193
Rawabi M Alsayer, Edward B De Vol, Amani Almeharish, Areej Alfattani, Alaa J Alghamdi, Luluh Behlal AlBehlal, Shatha Alhaddab, Yasmin Altwaijri
Purpose: Breast cancer is the most common cancer among women in the Saudi Arabia, and over 50% of the cases are detected at a late stage. This study aimed to estimate population attributable risk percentage (PAR%) of modifiable lifestyle risk factors for breast cancer in Saudi Arabia.
Patients and methods: A secondary analysis of previously published papers was performed . Relative risks (RR) and odds ratios (OR) were obtained from published international epidemiological studies, and the prevalence of each risk factor in Saudi Arabia was obtained from various sources (eg, national surveys and published literature) to calculate PAR%. A nomogram was used to visually translate the RRs/ORs and their prevalence into PAR% using a practical tool.
Results: Seven modifiable lifestyle risk factors for breast cancer were identified in Saudi Arabia. The identified risk factors included lack of physical activity (sedentary lifestyle), oral contraception (current use), obesity (postmenopausal), hormone replacement therapy (current use), passive smoking, age at first birth (≥ 35 years), and tobacco smoking (current or daily smoking). The PAR% for these risk factors ranged from 0.5% for tobacco smoking to 23.1% for a lack of physical activity. Few modifiable lifestyle risk factors were excluded from this study, due to limited nor unavailable data in Saudi Arabia (eg, alcohol consumption, breastfeeding patterns and childbearing patterns, obesity according to menopausal status, and night-shift work).
Conclusion: Physical inactivity has the most significant modifiable health impact and is a major risk factor for breast cancer. Removing this risk factor would reduce the prevalence of breast cancer in the Saudi population by 23%. There is an immense need to prioritize cancer control strategies based on local needs, current data on cancer risk factors, and the disease burden.
{"title":"Ranking of Modifiable Lifestyle Risk Factors for Breast Cancer in Saudi Women: Population Attributable Risk and Nomogram.","authors":"Rawabi M Alsayer, Edward B De Vol, Amani Almeharish, Areej Alfattani, Alaa J Alghamdi, Luluh Behlal AlBehlal, Shatha Alhaddab, Yasmin Altwaijri","doi":"10.2147/BCTT.S463193","DOIUrl":"10.2147/BCTT.S463193","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer is the most common cancer among women in the Saudi Arabia, and over 50% of the cases are detected at a late stage. This study aimed to estimate population attributable risk percentage (PAR%) of modifiable lifestyle risk factors for breast cancer in Saudi Arabia.</p><p><strong>Patients and methods: </strong>A secondary analysis of previously published papers was performed . Relative risks (RR) and odds ratios (OR) were obtained from published international epidemiological studies, and the prevalence of each risk factor in Saudi Arabia was obtained from various sources (eg, national surveys and published literature) to calculate PAR%. A nomogram was used to visually translate the RRs/ORs and their prevalence into PAR% using a practical tool.</p><p><strong>Results: </strong>Seven modifiable lifestyle risk factors for breast cancer were identified in Saudi Arabia. The identified risk factors included lack of physical activity (sedentary lifestyle), oral contraception (current use), obesity (postmenopausal), hormone replacement therapy (current use), passive smoking, age at first birth (≥ 35 years), and tobacco smoking (current or daily smoking). The PAR% for these risk factors ranged from 0.5% for tobacco smoking to 23.1% for a lack of physical activity. Few modifiable lifestyle risk factors were excluded from this study, due to limited nor unavailable data in Saudi Arabia (eg, alcohol consumption, breastfeeding patterns and childbearing patterns, obesity according to menopausal status, and night-shift work).</p><p><strong>Conclusion: </strong>Physical inactivity has the most significant modifiable health impact and is a major risk factor for breast cancer. Removing this risk factor would reduce the prevalence of breast cancer in the Saudi population by 23%. There is an immense need to prioritize cancer control strategies based on local needs, current data on cancer risk factors, and the disease burden.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02eCollection Date: 2024-01-01DOI: 10.2147/BCTT.S475007
Bing Yu, Zhimei Xing, Xiaoxuan Tian, Rui Feng
Background: Triple-negative breast cancer (TNBC) is recognized as the most aggressive molecular subtype of breast cancer. Recent studies have highlighted the complex role of autophagy in the pathogenesis of TNBC.
Methods: In this study, we evaluated 18,330 genes, including 1111 autophagy-related genes, (ARGs), across 579 TNBC samples from online databases. Differentially expressed ARGs in TNBC were identified using high-throughput RNA-seq data from the Cancer Genome Atlas (TCGA). Prognostic factors were examined through Cox regression and multivariate Cox analyses, with predictive efficacy assessed using receiver operating characteristic (ROC) curves. A nomogram integrating the risk signature with clinicopathological factors, such as TNM stage, was developed. Immunohistochemical analysis of clinical samples was also conducted.
Results: EIF4EBP1 and NPAS3 were significantly correlated with prognostic outcomes in patients with TNBC. Multivariate Cox regression analysis demonstrated that the expression levels of these two genes were accurate predictors of disease progression in TNBC samples from TCGA and the GSE31519 dataset. The efficacy of this predictive model was validated using ROC curve analysis and calibration plots, confirming its ability to accurately estimate the 1-, 2-, and 3-year survival rates for individuals with TNBC. Additionally, EIF4EBP1 and NPAS3 expression influenced drug sensitivity in TNBC cell lines, with notably lower NPAS3 expression in TNBC tissues, particularly in Stage III cases. This study is the first to report NPAS3 expression in patients with TNBC.
Conclusion: The autophagy-related genes EIF4EBP1 and NPAS3 may serve as independent prognostic factors for individuals with TNBC.
{"title":"A Prognostic Risk Signature of Two Autophagy-Related Genes for Predicting Triple-Negative Breast Cancer Outcomes.","authors":"Bing Yu, Zhimei Xing, Xiaoxuan Tian, Rui Feng","doi":"10.2147/BCTT.S475007","DOIUrl":"10.2147/BCTT.S475007","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is recognized as the most aggressive molecular subtype of breast cancer. Recent studies have highlighted the complex role of autophagy in the pathogenesis of TNBC.</p><p><strong>Methods: </strong>In this study, we evaluated 18,330 genes, including 1111 autophagy-related genes, (ARGs), across 579 TNBC samples from online databases. Differentially expressed ARGs in TNBC were identified using high-throughput RNA-seq data from the Cancer Genome Atlas (TCGA). Prognostic factors were examined through Cox regression and multivariate Cox analyses, with predictive efficacy assessed using receiver operating characteristic (ROC) curves. A nomogram integrating the risk signature with clinicopathological factors, such as TNM stage, was developed. Immunohistochemical analysis of clinical samples was also conducted.</p><p><strong>Results: </strong>EIF4EBP1 and NPAS3 were significantly correlated with prognostic outcomes in patients with TNBC. Multivariate Cox regression analysis demonstrated that the expression levels of these two genes were accurate predictors of disease progression in TNBC samples from TCGA and the GSE31519 dataset. The efficacy of this predictive model was validated using ROC curve analysis and calibration plots, confirming its ability to accurately estimate the 1-, 2-, and 3-year survival rates for individuals with TNBC. Additionally, EIF4EBP1 and NPAS3 expression influenced drug sensitivity in TNBC cell lines, with notably lower NPAS3 expression in TNBC tissues, particularly in Stage III cases. This study is the first to report NPAS3 expression in patients with TNBC.</p><p><strong>Conclusion: </strong>The autophagy-related genes EIF4EBP1 and NPAS3 may serve as independent prognostic factors for individuals with TNBC.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29eCollection Date: 2024-01-01DOI: 10.2147/BCTT.S271441
Kaitlyn O'Keefe, Neelam V Desai, Antoinette R Tan
The most common subtype of breast cancer is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, accounting for 65-70% of all breast cancer cases diagnosed in the United States. Until 2015, single-agent endocrine therapy (ET) was the recommended first-line treatment for metastatic HR-positive, HER2-negative breast cancer. However, the paradigm has since shifted, as targeted therapy is now recommended in combination with ET. The cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment of this breast cancer subtype, and combining either palbociclib, ribociclib, or abemaciclib with ET is now the standard first-line treatment for metastatic disease. Results of clinical trials in the metastatic setting have demonstrated that treatment with the combination of a CDK4/6 inhibitor and ET rather than ET alone is associated with longer overall survival, longer progression-free survival, and better objective response rates. Each of the CDK4/6 inhibitors has been investigated in combination with ET in patients with early-stage HR-positive, HER2-negative breast cancer who are at high risk of relapse. In October 2021, abemaciclib was the first CDK4/6 inhibitor approved in combination with ET by the US Food and Drug Administration for adjuvant treatment of patients with HR-positive, HER2-negative, high-risk early breast cancer. Herein, we provide practical guidance on the use of abemaciclib in combination with ET for HR-positive, HER2-negative, high-risk early breast cancer to assist clinicians in their day-to-day practice, and we review clinically relevant topics of dosing, side effect management, sequencing and optimal timing for initiation, and patient selection.
最常见的乳腺癌亚型是激素受体(HR)阳性、人表皮生长因子受体2(HER2)阴性的乳腺癌,占美国确诊的所有乳腺癌病例的65-70%。2015 年以前,单药内分泌治疗(ET)是转移性 HR 阳性、HER2 阴性乳腺癌的推荐一线治疗方法。不过,现在的治疗模式已经发生了转变,推荐将靶向治疗与 ET 结合使用。细胞周期蛋白依赖性激酶(CDK)4/6抑制剂彻底改变了这一乳腺癌亚型的治疗方法,将palbociclib、ribociclib或abemaciclib与ET联合使用现已成为治疗转移性疾病的标准一线疗法。转移性疾病的临床试验结果表明,CDK4/6 抑制剂与 ET 联合治疗比单独使用 ET 治疗的总生存期更长、无进展生存期更长、客观反应率更高。目前已对每种 CDK4/6 抑制剂与 ET 联合用于 HR 阳性、HER2 阴性的早期高复发风险乳腺癌患者进行了研究。2021 年 10 月,abemaciclib 成为美国食品和药物管理局批准的首个与 ET 联用的 CDK4/6 抑制剂,用于 HR 阳性、HER2 阴性、高风险早期乳腺癌患者的辅助治疗。在此,我们就阿巴西利(abemaciclib)联合 ET 治疗 HR 阳性、HER2 阴性、高危早期乳腺癌提供实用指南,以帮助临床医生开展日常工作,并回顾了剂量、副作用管理、用药顺序和最佳用药时机以及患者选择等临床相关主题。
{"title":"Practical Guidance on Abemaciclib in Combination with Adjuvant Endocrine Therapy for Treating Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative High-Risk Early Breast Cancer.","authors":"Kaitlyn O'Keefe, Neelam V Desai, Antoinette R Tan","doi":"10.2147/BCTT.S271441","DOIUrl":"10.2147/BCTT.S271441","url":null,"abstract":"<p><p>The most common subtype of breast cancer is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, accounting for 65-70% of all breast cancer cases diagnosed in the United States. Until 2015, single-agent endocrine therapy (ET) was the recommended first-line treatment for metastatic HR-positive, HER2-negative breast cancer. However, the paradigm has since shifted, as targeted therapy is now recommended in combination with ET. The cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment of this breast cancer subtype, and combining either palbociclib, ribociclib, or abemaciclib with ET is now the standard first-line treatment for metastatic disease. Results of clinical trials in the metastatic setting have demonstrated that treatment with the combination of a CDK4/6 inhibitor and ET rather than ET alone is associated with longer overall survival, longer progression-free survival, and better objective response rates. Each of the CDK4/6 inhibitors has been investigated in combination with ET in patients with early-stage HR-positive, HER2-negative breast cancer who are at high risk of relapse. In October 2021, abemaciclib was the first CDK4/6 inhibitor approved in combination with ET by the US Food and Drug Administration for adjuvant treatment of patients with HR-positive, HER2-negative, high-risk early breast cancer. Herein, we provide practical guidance on the use of abemaciclib in combination with ET for HR-positive, HER2-negative, high-risk early breast cancer to assist clinicians in their day-to-day practice, and we review clinically relevant topics of dosing, side effect management, sequencing and optimal timing for initiation, and patient selection.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}