Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2025.102885
Peilin Dai , Tianyi Song , Junzhi Liu , Zuer He , Xiaoli Wang , Ran Hu , Jiqiao Yang
Metaplastic breast cancer is a rare and heterogeneous subtype of breast cancer, associated with a poor prognosis. Its distinct biological behavior and morphological features contribute to resistance to standard treatment regimens. Hitherto, the optimal therapeutic strategy for metaplastic breast cancer remains underexplored. Herein, we review the literature on the treatment of metaplastic breast cancer, summarizing current local and systemic therapies, and discuss potential therapeutic targets and novel strategies based on its pathological and molecular characteristics. Targeted therapy and immunotherapy may provide more personalized treatment options, with the potential to improve the prognosis of this disease.
{"title":"Therapeutic strategies and landscape of metaplastic breast cancer","authors":"Peilin Dai , Tianyi Song , Junzhi Liu , Zuer He , Xiaoli Wang , Ran Hu , Jiqiao Yang","doi":"10.1016/j.ctrv.2025.102885","DOIUrl":"10.1016/j.ctrv.2025.102885","url":null,"abstract":"<div><div>Metaplastic breast cancer is a rare and heterogeneous subtype of breast cancer, associated with a poor prognosis. Its distinct biological behavior and morphological features contribute to resistance to standard treatment regimens. Hitherto, the optimal therapeutic strategy for metaplastic breast cancer remains underexplored. Herein, we review the literature on the treatment of metaplastic breast cancer, summarizing current local and systemic therapies, and discuss potential therapeutic targets and novel strategies based on its pathological and molecular characteristics. Targeted therapy and immunotherapy may provide more personalized treatment options, with the potential to improve the prognosis of this disease.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102885"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2025.102883
Yuqi Wu , Wenjin Shi , Chunyu Li , Xiangfei Liu , Yuchen Jiang , Yan Qiu , Qianming Chen , Xiaobo Luo
Radiotherapy and chemotherapy are widely employed as primary non-surgical cancer treatments; however, their non-selective cytotoxicity often leads to adverse events such as oral mucositis (OM), particularly in head and neck cancer therapies. International guidelines provide recommendations for managing chemoradiotherapy-induced OM in various clinical contexts. Subsequently, emerging researches have introduced evidence supporting novel approaches or existing regimens for OM prevention and treatment. The repurposing of established drugs has garnered significant interest due to its shorter development timeline, improved safety profiles, and lower costs compared to new drug development. For example, clinical trials assessing established drugs such as melatonin, clonidine, and pentoxifylline indicate promising potential for managing OM. Additionally, several emerging pharmacological interventions have demonstrated considerable efficacy; SAMITAL and rhIL-11 are supported by phase II clinical trials and prospective studies, while probiotics like Streptococcus salivarius K12 and curcumin have shown effectiveness in randomized clinical trials. Furthermore, recent high-level studies have reinforced the efficacy of non-pharmacological interventions, such as photobiomodulation (PBM) and cryotherapy, over the past two years. In all, given the evidence supporting different strategies, PBM and oral cryotherapy are highly recommended for managing OM when feasible. Topical clonidine, melatonin, oral pentoxifylline, topical SAMITAL or rhIL-11, oral SsK12, and curcumin may also be utilized but would benefit from validation in larger trials. Besides, Verbascoside, Palifermin, Amifostine, and Avasopasem manganese can be suggested for OM management, while the side effects should be monitored. The accessibility and cost/effectiveness of specific managing strategies of OM should be considered when selecting appropriate options.
放疗和化疗被广泛用作主要的非手术癌症治疗方法；然而，它们的非选择性细胞毒性往往会导致口腔黏膜炎（OM）等不良反应，尤其是在头颈部癌症治疗中。国际指南为在各种临床情况下处理化放疗引起的口腔黏膜炎提供了建议。随后，新出现的研究为预防和治疗口腔粘膜炎提出了支持新方法或现有方案的证据。与新药开发相比，既有药物的再利用具有开发时间短、安全性更好、成本更低等优点，因此备受关注。例如，评估褪黑素、氯尼丁和喷托非利兰等老药的临床试验表明，这些药物在控制 OM 方面具有广阔的潜力。此外，一些新出现的药物干预措施已显示出相当大的疗效；SAMITAL 和 rhIL-11 已获得 II 期临床试验和前瞻性研究的支持，而唾液链球菌 K12 和姜黄素等益生菌已在随机临床试验中显示出疗效。此外，在过去两年中，近期的高级别研究也加强了非药物干预措施的疗效，如光生物调节（PBM）和冷冻疗法。总之，鉴于支持不同策略的证据，在可行的情况下，强烈建议使用光生物调节和口服冷冻疗法来治疗 OM。外用氯硝柳胺、褪黑素、口服喷托非瑞林、外用 SAMITAL 或 rhIL-11、口服 SsK12 和姜黄素也可用于治疗，但需要通过更大规模的试验进行验证。此外，还可建议使用马鞭草苷、帕利福明、阿米福斯汀和阿伐沙星锰来治疗 OM，但应监测其副作用。在选择合适的方案时，应考虑特定OM管理策略的可及性和成本/效果。
{"title":"Managing strategies of chemotherapy and radiotherapy-induced oral mucositis","authors":"Yuqi Wu , Wenjin Shi , Chunyu Li , Xiangfei Liu , Yuchen Jiang , Yan Qiu , Qianming Chen , Xiaobo Luo","doi":"10.1016/j.ctrv.2025.102883","DOIUrl":"10.1016/j.ctrv.2025.102883","url":null,"abstract":"<div><div>Radiotherapy and chemotherapy are widely employed as primary non-surgical cancer treatments; however, their non-selective cytotoxicity often leads to adverse events such as oral mucositis (OM), particularly in head and neck cancer therapies. International guidelines provide recommendations for managing chemoradiotherapy-induced OM in various clinical contexts. Subsequently, emerging researches have introduced evidence supporting novel approaches or existing regimens for OM prevention and treatment. The repurposing of established drugs has garnered significant interest due to its shorter development timeline, improved safety profiles, and lower costs compared to new drug development. For example, clinical trials assessing established drugs such as melatonin, clonidine, and pentoxifylline indicate promising potential for managing OM. Additionally, several emerging pharmacological interventions have demonstrated considerable efficacy; SAMITAL and rhIL-11 are supported by phase II clinical trials and prospective studies, while probiotics like Streptococcus salivarius K12 and curcumin have shown effectiveness in randomized clinical trials. Furthermore, recent high-level studies have reinforced the efficacy of non-pharmacological interventions, such as photobiomodulation (PBM) and cryotherapy, over the past two years. In all, given the evidence supporting different strategies, PBM and oral cryotherapy are highly recommended for managing OM when feasible. Topical clonidine, melatonin, oral pentoxifylline, topical SAMITAL or rhIL-11, oral SsK12, and curcumin may also be utilized but would benefit from validation in larger trials. Besides, Verbascoside, Palifermin, Amifostine, and Avasopasem manganese can be suggested for OM management, while the side effects should be monitored. The accessibility and cost/effectiveness of specific managing strategies of OM should be considered when selecting appropriate options.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102883"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2025.102879
Jinna Lin , Shuqi Zheng , Qiang Liu
Background
Ovarian function suppression (OFS) has emerged as a crucial adjuvant therapy for premenopausal breast cancer patients. Some patients fail to achieve complete OFS with commonly used OFS drugs. The definition of incomplete OFS remains unclear, and large-scale data on its incidence are lacking. This review provides a comprehensive overview of the definition, occurrence, impact on therapeutic efficacy and corresponding treatment measures for incomplete OFS.
Methods
We searched PubMed, Embase and Cochrane Library databases in recent twenty years with keywords as “ovarian function escape”, “incomplete OFS” and “estrogen breakthrough”, and carried out a snowballing of references to important literature. Clinical literature of premenopausal breast cancer patients treated with OFS was screened. The patient characteristics, definition and incidence of incomplete OFS, prognosis, interventions and other information were extracted.
Results
A total of 17 studies were included in the analysis, including RCTs, retrospective or prospective cohort studies and case reports. Literature indicates that the incidence of incomplete OFS is around 5–50 % when the estradiol (E2) threshold is set as 2.72 pg/mL, 10 pg/mL, 20 pg/mL, or 30 pg/mL. Young age, high body mass index (BMI), and no prior chemotherapy were the risk factors for incomplete OFS. The treatment of incomplete OFS included dose adjustments, alternative OFS drugs, or the adoption of other OFS measures.
Conclusions
The incomplete OFS rate decreased with the extension of treatment time. It is reasonable to monitor E2 levels to ensure successful OFS in the patients with high risk factors for incomplete OFS or with concurrent use of aromatase inhibitor (AI). Transient incomplete OFS seems to have no impact on prognosis, but sustained incomplete OFS needs personalized adjustment of treatment strategy to ensure complete OFS.
{"title":"Incomplete ovarian function suppression in premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonists","authors":"Jinna Lin , Shuqi Zheng , Qiang Liu","doi":"10.1016/j.ctrv.2025.102879","DOIUrl":"10.1016/j.ctrv.2025.102879","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian function suppression (OFS) has emerged as a crucial adjuvant therapy for premenopausal breast cancer patients. Some patients fail to achieve complete OFS with commonly used OFS drugs. The definition of incomplete OFS remains unclear, and large-scale data on its incidence are lacking. This review provides a comprehensive overview of the definition, occurrence, impact on therapeutic efficacy and corresponding treatment measures for incomplete OFS.</div></div><div><h3>Methods</h3><div>We searched PubMed, Embase and Cochrane Library databases in recent twenty years with keywords as “ovarian function escape”, “incomplete OFS” and “estrogen breakthrough”, and carried out a snowballing of references to important literature. Clinical literature of premenopausal breast cancer patients treated with OFS was screened. The patient characteristics, definition and incidence of incomplete OFS, prognosis, interventions and other information were extracted.</div></div><div><h3>Results</h3><div>A total of 17 studies were included in the analysis, including RCTs, retrospective or prospective cohort studies and case reports. Literature indicates that the incidence of incomplete OFS is around 5–50 % when the estradiol (E2) threshold is set as 2.72 pg/mL, 10 pg/mL, 20 pg/mL, or 30 pg/mL. Young age, high body mass index (BMI), and no prior chemotherapy were the risk factors for incomplete OFS. The treatment of incomplete OFS included dose adjustments, alternative OFS drugs, or the adoption of other OFS measures.</div></div><div><h3>Conclusions</h3><div>The incomplete OFS rate decreased with the extension of treatment time. It is reasonable to monitor E2 levels to ensure successful OFS in the patients with high risk factors for incomplete OFS or with concurrent use of aromatase inhibitor (AI). Transient incomplete OFS seems to have no impact on prognosis, but sustained incomplete OFS needs personalized adjustment of treatment strategy to ensure complete OFS.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102879"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2024.102868
Giuseppe Buono , Monica Capozzi , Roberta Caputo , Vincenzo Di Lauro , Daniela Cianniello , Michela Piezzo , Stefania Cocco , Claudia Martinelli , Annarita Verrazzo , Margherita Tafuro , Claudia Calderaio , Alessandra Calabrese , Francesco Nuzzo , Martina Pagliuca , Michelino De Laurentiis
Within the expanding therapeutic landscape for breast cancer (BC), metastatic breast cancer (MBC) remains virtually incurable and tend to develop resistance to conventional treatments ultimately leading to metastatic progression and death. Cellular immunotherapy (CI), particularly chimeric antigen receptor-engineered T (CAR-T) cells, has emerged as a promising approach for addressing this challenge. In the wake of their striking efficacy against hematological cancers, CAR-T cells have also been used where the clinical need is greatest – in patients with aggressive BCs. Unfortunately, current outcomes fall considerably short of replicating that success, primarily owing to the scarcity of tumor-specific antigens and the immunosuppressive microenvironment within BC. Herein, we provide an up-to-date overview of both preclinical and clinical data concerning the application of CAR-T cell therapy in BC. By surveying the existing literature, we discuss the prevailing constrains of this therapeutic approach and overview possible strategies to advance it in the context of breast malignancies. Possible approaches include employing synthetic biology to refine antigen targeting and mitigate off-target toxicity, utilizing logic-gated CAR constructs to enhance specificity, and leveraging armored CARs to remodel the tumor micro-environment. Temporal and spatial regulation of CAR-T cells using inducible gene switches and external triggers further improves safety and functionality. In addition, promoting T cell homing through chemokine receptor engineering and enhancing manufacturing processes with universal CAR platforms expand therapeutic applicability. These innovations not only address antigen escape and T cell exhaustion but also optimize the efficacy and safety profile of CAR-T cell therapy. We, therefore, outline a trajectory wherein CAR-T cells may evolve from a promising experimental approach to a standard modality in BC therapy.
在不断扩大的乳腺癌（BC）治疗范围内，转移性乳腺癌（MBC）仍然几乎无法治愈，而且往往会对常规治疗产生抗药性，最终导致转移和死亡。细胞免疫疗法（CI），尤其是嵌合抗原受体工程化T细胞（CAR-T），已成为应对这一挑战的一种前景广阔的方法。CAR-T细胞对血液肿瘤有显著疗效，因此也被用于临床需求最大的领域--侵袭性BC患者。遗憾的是，由于肿瘤特异性抗原的稀缺和 BC 病区的免疫抑制微环境，目前的研究结果远远无法复制这种成功。在本文中，我们将对CAR-T细胞疗法在BC中应用的临床前和临床数据进行最新概述。通过调查现有文献，我们讨论了这种治疗方法的主要限制因素，并概述了在乳腺恶性肿瘤中推进这种治疗方法的可能策略。可能的方法包括利用合成生物学来完善抗原靶向和减轻脱靶毒性，利用逻辑门控 CAR 构建来增强特异性，以及利用装甲 CAR 来重塑肿瘤微环境。利用可诱导基因开关和外部触发器对 CAR-T 细胞进行时间和空间调控，可进一步提高安全性和功能性。此外，通过趋化因子受体工程促进 T 细胞归巢，以及利用通用 CAR 平台改进生产工艺，也扩大了治疗的适用性。这些创新不仅解决了抗原逃逸和 T 细胞衰竭问题，还优化了 CAR-T 细胞疗法的疗效和安全性。因此，我们勾勒出了一条轨迹，CAR-T 细胞可能会从一种前景广阔的实验方法发展成为 BC 治疗的标准模式。
{"title":"CAR-T cell therapy for breast cancer: Current status and future perspective","authors":"Giuseppe Buono , Monica Capozzi , Roberta Caputo , Vincenzo Di Lauro , Daniela Cianniello , Michela Piezzo , Stefania Cocco , Claudia Martinelli , Annarita Verrazzo , Margherita Tafuro , Claudia Calderaio , Alessandra Calabrese , Francesco Nuzzo , Martina Pagliuca , Michelino De Laurentiis","doi":"10.1016/j.ctrv.2024.102868","DOIUrl":"10.1016/j.ctrv.2024.102868","url":null,"abstract":"<div><div>Within the expanding therapeutic landscape for breast cancer (BC), metastatic breast cancer (MBC) remains virtually incurable and tend to develop resistance to conventional treatments ultimately leading to metastatic progression and death. Cellular immunotherapy (CI), particularly chimeric antigen receptor-engineered T (CAR-T) cells, has emerged as a promising approach for addressing this challenge. In the wake of their striking efficacy against hematological cancers, CAR-T cells have also been used where the clinical need is greatest – in patients with aggressive BCs. Unfortunately, current outcomes fall considerably short of replicating that success, primarily owing to the scarcity of tumor-specific antigens and the immunosuppressive microenvironment within BC. Herein, we provide an up-to-date overview of both preclinical and clinical data concerning the application of CAR-T cell therapy in BC. By surveying the existing literature, we discuss the prevailing constrains of this therapeutic approach and overview possible strategies to advance it in the context of breast malignancies. Possible approaches include employing synthetic biology to refine antigen targeting and mitigate off-target toxicity, utilizing logic-gated CAR constructs to enhance specificity, and leveraging armored CARs to remodel the tumor micro-environment. Temporal and spatial regulation of CAR-T cells using inducible gene switches and external triggers further improves safety and functionality. In addition, promoting T cell homing through chemokine receptor engineering and enhancing manufacturing processes with universal CAR platforms expand therapeutic applicability. These innovations not only address antigen escape and T cell exhaustion but also optimize the efficacy and safety profile of CAR-T cell therapy. We, therefore, outline a trajectory wherein CAR-T cells may evolve from a promising experimental approach to a standard modality in BC therapy.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102868"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2025.102888
Keiji Sugiyama , Ian Chau
Claudins (CLDNs) play a crucial and indispensable role as fundamental components within the structure of tight junctions. Due to the distinct and unique distribution pattern exhibited by CLDNs in both normal and malignant tissues, these proteins have garnered significant attention as pivotal targets for systemic anti-cancer therapy and as noteworthy diagnostic markers. This review provides a comprehensive and detailed elucidation of the fundamental understanding surrounding CLDNs, their intricate expression patterns, the potential role they play in cancer diagnosis and therapeutic potentials; all encapsulated within a succinct summary of the cutting-edge advancements and the information derived from various clinical trials.
{"title":"Claudins as diagnostic tools and therapeutic targets—Glimpse of the horizon","authors":"Keiji Sugiyama , Ian Chau","doi":"10.1016/j.ctrv.2025.102888","DOIUrl":"10.1016/j.ctrv.2025.102888","url":null,"abstract":"<div><div>Claudins (CLDNs) play a crucial and indispensable role as fundamental components within the structure of tight junctions. Due to the distinct and unique distribution pattern exhibited by CLDNs in both normal and malignant tissues, these proteins have garnered significant attention as pivotal targets for systemic anti-cancer therapy and as noteworthy diagnostic markers. This review provides a comprehensive and detailed elucidation of the fundamental understanding surrounding CLDNs, their intricate expression patterns, the potential role they play in cancer diagnosis and therapeutic potentials; all encapsulated within a succinct summary of the cutting-edge advancements and the information derived from various clinical trials.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102888"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2025.102880
Stavroula L. Kastora , Eirini Pantiora , Yong Hwa Hong , Meenakshi Veeramani , Hatem A Azim Jr , Rima Chakrabarti , Jürgen Geisler , Ann Knoop , Matteo Lambertini , Barbro Linderholm , Icro Meattini , Ann H Partridge , Ines Vaz-Luis , Denise Vorburger , Gabriella Yongue , Andreas Karakatsanis , Antonios Valachis
<div><h3>Importance</h3><div>Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symptoms, adversely affecting drug compliance. Topical estrogen (TE) has been proposed for symptom management, given its’ local application and presumed reduced bioavailability, however its oncological safety remains uncertain.</div></div><div><h3>Objective</h3><div>The present systematic review, <em>meta</em>-analysis and expert panel review aimed to evaluate the strength of the available evidence on the risk of recurrence and mortality when TE is utilised in congruence with TAM or AI treatment, among BC survivors.</div></div><div><h3>Data Sources</h3><div>Six databases and two prospective registers, were interrogated from inception to January 3rd, 2024. Search terms were Breast cancer AND Hormone replacement therapy AND topical/vaginal oestrogen AND recurrence/mortality.</div></div><div><h3>Study selection</h3><div>All study designs reporting the use vs. non-use of TE in breast cancer survivors receiving adjuvant endocrine treatment were included. Six observational studies were deemed eligible for inclusion.</div></div><div><h3>Data extraction and synthesis</h3><div>Sources of heterogeneity were explored using subgroup analysis by risk of bias, median follow-up period, node positivity and menopausal status. Trial sequential analysis was performed to quantify outcome reliability. A global expert panel was called to deliberate on the data, pinpoint areas of limited understanding, and determine the most important areas for future research.</div></div><div><h3>Main outcomes and measures</h3><div>Risk ratio effect sizes (RR) and corresponding 95 % Confidence Intervals (CI) of breast cancer recurrence and mortality in survivors on endocrine treatment (TAM and/or AI) exposed to TE were reported. Expert panel appraisal of <em>meta</em>-analysis evidence with definition of current knowledge gaps and future research aims.</div></div><div><h3>Results</h3><div>In 38 050 female patients receiving adjuvant endocrine treatment, of whom 1805 had been exposed to TE, TE exposure of those on AI, did not increase all-cause mortality (RR 0.99 [95 %CI 0.58, 1.69], I<sup>2</sup> = 81 %, P = 0.96; moderate GRADE certainty). However, such exposure may convey an increased risk of recurrence (RR 2.51 [95 % CI 1.10, 5.72], I<sup>2</sup> = 9 %, P = 0.03; low-GRADE certainty). Exposure to TE during TAM did not increase either recurrence risk or all-cause mortality. Clinical factors such as lymph node positivity at the time of diagnosis and menopausal status and follow-up time appeared to be significant confounders.</div></div><div><h3>Conclusions and relevance</h3><div>The use of TE does not appear to increase either recurrence or mortality risk among BC survivors treated with TAM. An increased recurrence risk, without an increase in mortality,
{"title":"Safety of topical estrogen therapy during adjuvant endocrine treatment among patients with breast cancer: A meta-analysis based expert panel discussion","authors":"Stavroula L. Kastora , Eirini Pantiora , Yong Hwa Hong , Meenakshi Veeramani , Hatem A Azim Jr , Rima Chakrabarti , Jürgen Geisler , Ann Knoop , Matteo Lambertini , Barbro Linderholm , Icro Meattini , Ann H Partridge , Ines Vaz-Luis , Denise Vorburger , Gabriella Yongue , Andreas Karakatsanis , Antonios Valachis","doi":"10.1016/j.ctrv.2025.102880","DOIUrl":"10.1016/j.ctrv.2025.102880","url":null,"abstract":"<div><h3>Importance</h3><div>Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symptoms, adversely affecting drug compliance. Topical estrogen (TE) has been proposed for symptom management, given its’ local application and presumed reduced bioavailability, however its oncological safety remains uncertain.</div></div><div><h3>Objective</h3><div>The present systematic review, <em>meta</em>-analysis and expert panel review aimed to evaluate the strength of the available evidence on the risk of recurrence and mortality when TE is utilised in congruence with TAM or AI treatment, among BC survivors.</div></div><div><h3>Data Sources</h3><div>Six databases and two prospective registers, were interrogated from inception to January 3rd, 2024. Search terms were Breast cancer AND Hormone replacement therapy AND topical/vaginal oestrogen AND recurrence/mortality.</div></div><div><h3>Study selection</h3><div>All study designs reporting the use vs. non-use of TE in breast cancer survivors receiving adjuvant endocrine treatment were included. Six observational studies were deemed eligible for inclusion.</div></div><div><h3>Data extraction and synthesis</h3><div>Sources of heterogeneity were explored using subgroup analysis by risk of bias, median follow-up period, node positivity and menopausal status. Trial sequential analysis was performed to quantify outcome reliability. A global expert panel was called to deliberate on the data, pinpoint areas of limited understanding, and determine the most important areas for future research.</div></div><div><h3>Main outcomes and measures</h3><div>Risk ratio effect sizes (RR) and corresponding 95 % Confidence Intervals (CI) of breast cancer recurrence and mortality in survivors on endocrine treatment (TAM and/or AI) exposed to TE were reported. Expert panel appraisal of <em>meta</em>-analysis evidence with definition of current knowledge gaps and future research aims.</div></div><div><h3>Results</h3><div>In 38 050 female patients receiving adjuvant endocrine treatment, of whom 1805 had been exposed to TE, TE exposure of those on AI, did not increase all-cause mortality (RR 0.99 [95 %CI 0.58, 1.69], I<sup>2</sup> = 81 %, P = 0.96; moderate GRADE certainty). However, such exposure may convey an increased risk of recurrence (RR 2.51 [95 % CI 1.10, 5.72], I<sup>2</sup> = 9 %, P = 0.03; low-GRADE certainty). Exposure to TE during TAM did not increase either recurrence risk or all-cause mortality. Clinical factors such as lymph node positivity at the time of diagnosis and menopausal status and follow-up time appeared to be significant confounders.</div></div><div><h3>Conclusions and relevance</h3><div>The use of TE does not appear to increase either recurrence or mortality risk among BC survivors treated with TAM. An increased recurrence risk, without an increase in mortality, ","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102880"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2025.102886
Juan Martin-Liberal , Iván Márquez-Rodas , Pablo Cerezuela-Fuentes , Ainara Soria , Fernando Garicano , Javier Medina , Regina García Galindo , Juana Oramas , José Luis Manzano , Mayte Delgado , Javier Valdivia , Pedro Sanchez
The global incidence of metastatic melanoma with BRAF mutations, characterized by aggressive behavior and poor prognosis, is rising. Recent treatment advances, including immune checkpoint inhibitors (ICI) and targeted therapies (TT) such as BRAF and MEK inhibitors, have significantly enhanced patient outcomes. Although guidelines recommend sequencing strategies, real-world implementation can be influenced by clinical scenarios. This article highlights the importance of tailored treatment strategies, emphasizing that the decision to initiate immunotherapy (IT) or TT hinges on multiple factors, including tumor burden, LDH levels, presence of brain metastases, and patient symptomatic status. Managing brain metastases also poses a challenge, as these patients are typically excluded from pivotal clinical trials. While insights from phase II studies provide some guidance, there is a critical need for more quality data to inform comprehensive recommendations. Furthermore, although triple therapy combining IT and TT was initially thought to be promising, it has failed to clearly demonstrate benefit over current treatments. For all these reasons, there is an imperative need for further research on biomarkers and predictive factors, as well as real-world studies, that will help tailor treatment strategies across diverse patient subsets, thereby refining therapeutic approaches for BRAF-mutated metastatic melanoma.
{"title":"Challenges and perspectives in the management of BRAF-mutated metastatic melanoma: Systemic treatment sequencing and brain metastases","authors":"Juan Martin-Liberal , Iván Márquez-Rodas , Pablo Cerezuela-Fuentes , Ainara Soria , Fernando Garicano , Javier Medina , Regina García Galindo , Juana Oramas , José Luis Manzano , Mayte Delgado , Javier Valdivia , Pedro Sanchez","doi":"10.1016/j.ctrv.2025.102886","DOIUrl":"10.1016/j.ctrv.2025.102886","url":null,"abstract":"<div><div>The global incidence of metastatic melanoma with BRAF mutations, characterized by aggressive behavior and poor prognosis, is rising. Recent treatment advances, including immune checkpoint inhibitors (ICI) and targeted therapies (TT) such as BRAF and MEK inhibitors, have significantly enhanced patient outcomes. Although guidelines recommend sequencing strategies, real-world implementation can be influenced by clinical scenarios. This article highlights the importance of tailored treatment strategies, emphasizing that the decision to initiate immunotherapy (IT) or TT hinges on multiple factors, including tumor burden, LDH levels, presence of brain metastases, and patient symptomatic status. Managing brain metastases also poses a challenge, as these patients are typically excluded from pivotal clinical trials. While insights from phase II studies provide some guidance, there is a critical need for more quality data to inform comprehensive recommendations. Furthermore, although triple therapy combining IT and TT was initially thought to be promising, it has failed to clearly demonstrate benefit over current treatments. For all these reasons, there is an imperative need for further research on biomarkers and predictive factors, as well as real-world studies, that will help tailor treatment strategies across diverse patient subsets, thereby refining therapeutic approaches for BRAF-mutated metastatic melanoma.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102886"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2025.102884
Ana Isabel Sebastião , Gonçalo Simões , Filomena Oliveira , Daniela Mateus , Amílcar Falcão , Mylène A. Carrascal , Célia Gomes , Bruno Neves , Maria Teresa Cruz
Breast cancer is the second most commonly diagnosed cancer in women and the fifth leading cause of cancer-related deaths worldwide. It is a highly heterogeneous disease, consisting of multiple subtypes that vary significantly in clinical characteristics and survival outcomes. Triple-negative breast cancer (TNBC) is a particularly aggressive and challenging subtype of breast cancer. Several immunotherapeutic approaches have been tested in patients with TNBC to improve disease outcomes, including the administration of dendritic cell (DC)-based vaccines. DCs are a heterogeneous cell population that play a crucial role in bridging the innate and adaptive immune systems. Therefore, DCs have been increasingly used in cancer vaccines due to their ability to prime and boost antigen specific T-cell immune responses. This review aims to provide a comprehensive overview of TNBC, including potential targets and pharmacological strategies, as well as an overview of DCs and their relevance in TNBC. In addition, we review ongoing clinical trials and shed light on the evolving landscape of DC-based immunotherapy for TNBC.
{"title":"Dendritic cells in triple-negative breast cancer: From pathophysiology to therapeutic applications","authors":"Ana Isabel Sebastião , Gonçalo Simões , Filomena Oliveira , Daniela Mateus , Amílcar Falcão , Mylène A. Carrascal , Célia Gomes , Bruno Neves , Maria Teresa Cruz","doi":"10.1016/j.ctrv.2025.102884","DOIUrl":"10.1016/j.ctrv.2025.102884","url":null,"abstract":"<div><div>Breast cancer is the second most commonly diagnosed cancer in women and the fifth leading cause of cancer-related deaths worldwide. It is a highly heterogeneous disease, consisting of multiple subtypes that vary significantly in clinical characteristics and survival outcomes. Triple-negative breast cancer (TNBC) is a particularly aggressive and challenging subtype of breast cancer. Several immunotherapeutic approaches have been tested in patients with TNBC to improve disease outcomes, including the administration of dendritic cell (DC)-based vaccines. DCs are a heterogeneous cell population that play a crucial role in bridging the innate and adaptive immune systems. Therefore, DCs have been increasingly used in cancer vaccines due to their ability to prime and boost antigen specific T-cell immune responses. This review aims to provide a comprehensive overview of TNBC, including potential targets and pharmacological strategies, as well as an overview of DCs and their relevance in TNBC. In addition, we review ongoing clinical trials and shed light on the evolving landscape of DC-based immunotherapy for TNBC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102884"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2025.102882
Isabella Michelon , Caio E.R. Castro , Thiago Madeira , Maria Inez Dacoregio , Carlos Stecca , Leonardo R. Soares , Anwaar Saeed , Maysa Vilbert , Ludimila Cavalcante
Background
Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated meta-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease.
Methods
A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD). We used random effects models for all statistical analyses.
Results
We included 18 studies with 786 HER2-positive BC patients with CNS involvement (16 studies with 750 BMs patients and three studies with 36 LMD patients). We observed high overall antitumor responses (objective response rate [ORR], 60.4 %; disease control rate [DCR], 94.4 %; and clinical benefit rate [CBR], 79.3 %) and a 12-month PFS of 64.7 % and OS of 82.7 %. Intracranial ORR, DCR, and CBR were seen in 62.2 %, 88.6 %, and 68.6 % of patients, respectively, and 67.4 % achieved intracranial PFS at 12 months. Both stable and active BMs subgroups derived similar benefit from T-DXd. Better intracranial responses were seen for 33 patients with untreated BMs compared to 56 patients with previously treated or progressing lesions (odds ratio 3.82, 95 % confidence interval 1.3–10.8, p = 0.01). For the LMD group, T-DXd elicited intracranial ORR and CBR in 59.4 % and 94.1 % of patients, respectively.
Conclusions
This updated meta-analysis continues to support the overall and intracranial activity of T-DXd in patients with HER2-positive BC and CNS involvement, including those with LMD.
{"title":"Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: A systematic review and updated meta-analysis","authors":"Isabella Michelon , Caio E.R. Castro , Thiago Madeira , Maria Inez Dacoregio , Carlos Stecca , Leonardo R. Soares , Anwaar Saeed , Maysa Vilbert , Ludimila Cavalcante","doi":"10.1016/j.ctrv.2025.102882","DOIUrl":"10.1016/j.ctrv.2025.102882","url":null,"abstract":"<div><h3>Background</h3><div>Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated <em>meta</em>-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease.</div></div><div><h3>Methods</h3><div>A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD). We used random effects models for all statistical analyses.</div></div><div><h3>Results</h3><div>We included 18 studies with 786 HER2-positive BC patients with CNS involvement (16 studies with 750 BMs patients and three studies with 36 LMD patients). We observed high overall antitumor responses (objective response rate [ORR], 60.4 %; disease control rate [DCR], 94.4 %; and clinical benefit rate [CBR], 79.3 %) and a 12-month PFS of 64.7 % and OS of 82.7 %. Intracranial ORR, DCR, and CBR were seen in 62.2 %, 88.6 %, and 68.6 % of patients, respectively, and 67.4 % achieved intracranial PFS at 12 months. Both stable and active BMs subgroups derived similar benefit from T-DXd. Better intracranial responses were seen for 33 patients with untreated BMs compared to 56 patients with previously treated or progressing lesions (odds ratio 3.82, 95 % confidence interval 1.3–10.8, p = 0.01). For the LMD group, T-DXd elicited intracranial ORR and CBR in 59.4 % and 94.1 % of patients, respectively.</div></div><div><h3>Conclusions</h3><div>This updated <em>meta</em>-analysis continues to support the overall and intracranial activity of T-DXd in patients with HER2-positive BC and CNS involvement, including those with LMD.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102882"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2024.102878
Philipp Melhorn, Markus Raderer, Barbara Kiesewetter
Neuroendocrine tumors (NET) of the lung are a slowly growing subtype of lung cancer that has a different treatment paradigm than aggressive and more common forms of lung neuroendocrine neoplasms (NEN) like small cell lung cancer (SCLC). Current guidelines for metastatic lung NET advocate a handful of treatment options, including somatostatin analogs (SSA), everolimus, temozolomide- or platin-based chemotherapy, and peptide receptor radionuclide therapy (PRRT). However, there is no clear treatment sequence, and the therapy of choice may depend on several factors such as tumor grade / growth rate, tumor burden / symptoms, disease progression status, and somatostatin receptor (SSTR) expression. In order to tailor treatment to each individual patient, the latest scientific findings and patient-specific clinical features must be considered together. This review critically evaluates the available evidence with regards to relevant patient characteristics, inclusion and exclusion criteria, and outcome metrics of clinical trials given the presumed natural disease course. Specific patient subgroups with an unmet therapeutic need are identified and discussed in the context of ongoing clinical trials.
{"title":"Selecting systemic treatment for metastatic neuroendocrine tumors of the lung—current evidence and clinical implications","authors":"Philipp Melhorn, Markus Raderer, Barbara Kiesewetter","doi":"10.1016/j.ctrv.2024.102878","DOIUrl":"10.1016/j.ctrv.2024.102878","url":null,"abstract":"<div><div>Neuroendocrine tumors (NET) of the lung are a slowly growing subtype of lung cancer that has a different treatment paradigm than aggressive and more common forms of lung neuroendocrine neoplasms (NEN) like small cell lung cancer (SCLC). Current guidelines for metastatic lung NET advocate a handful of treatment options, including somatostatin analogs (SSA), everolimus, temozolomide- or platin-based chemotherapy, and peptide receptor radionuclide therapy (PRRT). However, there is no clear treatment sequence, and the therapy of choice may depend on several factors such as tumor grade / growth rate, tumor burden / symptoms, disease progression status, and somatostatin receptor (SSTR) expression. In order to tailor treatment to each individual patient, the latest scientific findings and patient-specific clinical features must be considered together. This review critically evaluates the available evidence with regards to relevant patient characteristics, inclusion and exclusion criteria, and outcome metrics of clinical trials given the presumed natural disease course. Specific patient subgroups with an unmet therapeutic need are identified and discussed in the context of ongoing clinical trials.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102878"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号