Esophageal cancer screening,early detection and treatment:Current insights and future directions

Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

An Improved Fully Automated Breast Cancer Detection and Classification System

More than 500,000 patients are diagnosed with breast cancer annually.Authorities worldwide reported a death rate of 11.6%in 2018.Breast tumors are considered a fatal disease and primarily affect middle-aged women.Various approaches to identify and classify the disease using different technologies,such as deep learning and image segmentation,have been developed.Some of these methods reach 99%accuracy.However,boosting accuracy remains highly important as patients’lives depend on early diagnosis and specified treatment plans.This paper presents a fully computerized method to detect and categorize tumor masses in the breast using two deep-learning models and a classifier on different datasets.This method specifically uses ResNet50 and AlexNet,convolutional neural networks(CNNs),for deep learning and a K-Nearest-Neighbor(KNN)algorithm to classify data.Various experiments have been conducted on five datasets:the Mammographic Image Analysis Society(MIAS),Breast Cancer Histopathological Annotation and Diagnosis(BreCaHAD),King Abdulaziz University Breast Cancer Mammogram Dataset(KAU-BCMD),Breast Histopathology Images(BHI),and Breast Cancer Histopathological Image Classification(BreakHis).These datasets were used to train,validate,and test the presented method.The obtained results achieved an average of 99.38%accuracy,surpassing other models.Essential performance quantities,including precision,recall,specificity,and F-score,reached 99.71%,99.46%,98.08%,and 99.67%,respectively.These outcomes indicate that the presented method offers essential aid to pathologists diagnosing breast cancer.This study suggests using the implemented algorithm to support physicians in analyzing breast cancer correctly.

Preventing breast cancer in LMICs via screening and/or early detection: The real and the surreal

To review the present status of breast cancer(BC) screening/early detection in low- and middle-income countries(LMICs) and identify the way forward, an open focused search for articles was undertaken in Pub Med, Google Scholar and Google, and using a snowball technique, further articles were obtained from the reference list of initial search results. In addition, a query was put up on Research Gate to obtain more references and find out the general opinion of experts on the topic. Experts were also personally contacted for their opinion. Breast cancer(BC) is the most common cancer in women in the world. The rise in incidence is highest in LMICs where the incidence has often been much lower than high-income countries. In spite of more women dying of cancer than pregnancy or childbirth related causes in LMICs, most of the focus and resources are devoted to maternal health. Also, the majority of women in LMICs present at late stages to a hospital to initiate treatment. A number of trials have been conducted in various LMICs regarding the use of clinical breast examination and mammography in various combinations to understand the best ways of implementing a population level screening/early detection of BC; nevertheless, more research in this area is badly needed for different LMIC specific contexts. No-tably, very few LMICs have national level programs for BC prevention via screening/early detection and even stage reduction is not on the public health agenda. This is in addition to other barriers such as lack of awareness among women regarding BC and the presence of stigma, inappropriate attitudes and lack of following proper screening behavior, such as conducting breast self-examinations. The above is mixed with the apathy and lack of awareness of policy makers regarding the fact that BC prevention is much more cost-effective and humane than BC treatment. Implementation of population level programs for screening/early detection of BC, along with use of ways to improve awareness of women regarding BC, can prove critical in stemming the increasing burden of BC in LMICs. Use of newer modalities such as ultrasonography which is more suited to LMIC populations and use of m Health for awareness creation and increasing screening compliance are much needed extra additions to the overall agenda of LMICs in preventing BC.

Interpretation of specification for breast cancer screening,early diagnosis,and treatment management in Chinese women

Breast cancer has become the most common malignant tumor worldwide.However,the survival rate of breast cancer patients in China is 8%lower compared to that in European and American countries.Insufficient screen-ing coverage and low rate of early detection are key problems.Therefore,it is imperative to develop a set of guidelines for breast cancer screening,early diagnosis,and treatment strategies suitable for Chinese women.The National Health Commission,the National Cancer Center,and the National Cancer Quality Control Center col-lectively organized a committee of specialists with multidisciplinary backgrounds in breast surgery,oncology,radiotherapy,diagnostic imaging,ultrasound,pathology,epidemiology,and health economics.The committee collectively published"China Breast Cancer Screening,Early Diagnosis and Treatment Specification",in which the committee outlined a set of strategies of breast cancer screening,early diagnosis,and treatment suitable for China’s national conditions.The strategies were formulated based on clinical experience in breast cancer preven-tion and treatment,characteristics of breast cancer patients in China,and socioeconomic conditions.The purpose of this article is to provide an interpretation of the above guidelines as a reference for breast cancer screening.

A double constrained robust capon beamforming based imaging method for early breast cancer detection

Ultra-wideband （UWB） microwave images are proposed for detecting small malignant breast tumors based on the large contrast of electric parameters between a malignant tumor and normal breast tissue. In this study, an antenna array composed of 9 antennas is applied to the detection. The double constrained robust capon beamforming （DCRCB） algorithm is used for reconstructing the breast image due to its better stability and high signal-to-interference-plus-noise ratio （SINR）. The successful detection of a tumor of 2 mm in diameter shown in the reconstruction demonstrates the robustness of the DCRCB beamforming algorithm. This study verifies the feasibility of detecting small breast tumors by using the DCRCB imaging algorithm.

A Study of Quasi-Monochromatic X-Ray Sources for Breast Cancer Early Detection

Objectives: Early detection and treatment provide the opportunity to decrease the mortality rate from breast cancer. Quasi-monochromatic technique can enhance low contrast lesion detection by eliminating beam-hardening artifacts. We hypothesized that this technique would be feasible and can be used to assist in breast cancer early detection. Methods: The performance of stationary Digital Breast Tomosynthesis with quasi-monochromatic X-ray sources was evaluated using both simulated and physical phantoms. Normalized spectra in the fraction of total photons vs. photon energy were generated. Results: As expected, the peaked energies from sources, from smallest to largest, are Mo/Mo, W/Ag-1000, and W/Ce-10, W/Ce-100. For contrast vs. noise standard deviation on the simulated CIRS phantom, W/Ce-100 and W/Ce-10 have similar performance on both low and high contrast objects. For low contrast object, W/Ce-100 is barely noticeably better than W/Ce-10, and they are better than both W/Ag-1000 and Mo/Mo. For high contrast objects W/Ce-10 is slightly better than W/Ce-100. The spectra of the implemented W/Ce-10 X-ray source were measured, which matched the simulation well. The contrast noise ratios of reconstructed objects in American College of Radiology mammographic phantom with and without using W/Ce-10 combination are 7.1 and 5.4, respectively. Conclusions: The combination of stationary digital breast tomosynthesis and quasi-monochromatic technique can compensate the loss of X-ray flux due to heavy K-edge filtering. This technique can enable the stationary DBT scanners to operate at acceptable scanning times with better low contrast lesion detectability. Advances in Knowledge: The stationary digital breast tomosynthesis can provide high quality images within short scanning time by using X-ray source array, which makes quasi-monochromatic technique feasible.

Chinese national clinical practice guidelines on prevention,diagnosis and treatment of early colorectal cancer

Background:The incidence and mortality of colorectal cancer(CRC)in China are increasing in recent years.The clarified pathogenesis and detectable precancerous lesions of CRC make it possible to prevent,screen,and diagnose CRC at an early stage.With the development of endoscopic and surgical techniques,the choice of treatment for early CRC is also worth further discussion,and accordingly,a standard follow-up program after treatment needs to be established.Methods:This clinical practice guideline(CPG)was developed following the recommended process of the World Health Organization,adopting Grading of Recommendations Assessment,Development and Evaluation(GRADE)in assessing evidence quality,and using the Evidence to Decision framework to formulate clinical recommendations,thereby minimizing bias and increasing transparency of the CPG development process.We used the Reporting Items for practice Guidelines in HealThcare(RIGHT)statement and Appraisal of Guidelines for Research and Evaluation II(AGREE II)as reporting and conduct guides to ensure the guideline’s completeness and transparency.Results:This CPG comprises 46 recommendations concerning prevention,screening,diagnosis,treatment,and surveillance of CRC.In these recommendations,we have indicated protective and risk factors for CRC and made recommendations for chemoprevention.We proposed a suitable screening program for CRC based on the Chinese context.We also provided normative statements for the diagnosis,treatment,and surveillance of CRC based on existing clinical evidence and guidelines.Conclusions:The 46 recommendations in this CPG are formed with consideration for stakeholders’values and preferences,feasibility,and acceptability.Recommendations are generalizable to resource-limited settings with similar CRC epidemiology pattern as China.

At-home cancer screening:a solution for China and other developing countries with a large population and limited number of healthcare practitioners

Five-year survival rate for patients with all cancers combined, in China, is only 30.9%, which is much lower than those in developed countries. The three main reasons for the low cancer curative rates in China include differences in the spectrum of cancer types, in early detection rates, and in the percentage of cancer patients receiving standardized treatment between China and developed countries.The most important mechanism for improving the curative rate is to improve early detection rates of major cancers in China using novel and affordable technologies that can be operated at home by the patients themselves.This attempt could be helpful in setting up a practical example for other developing countries with limited medical resources and a limited number of healthcare practitioners.

循环肿瘤DNA检测在乳腺癌早期诊治中的应用进展

乳腺癌作为全球女性第二大癌症致死原因,其高发病率与致死率给全球女性的健康带来了极大威胁。循环肿瘤DNA(ctDNA)是肿瘤细胞所释放的DNA片段,可以反映肿瘤负荷及肿瘤基因组的突变情况。ctDNA是肿瘤复发的灵敏且特异的生物标志物。ctDNA检测作为一种新兴的液体活检技术,在检测分子残留病灶和治疗反应监测方面具有实用性,可帮助临床医生优化治疗和监测策略。ctDNA检测在临床应用中面临一些挑战,包括检测灵敏度的限制、ctDNA水平的波动及其他因素的干扰。该文综述了近年来ctDNA检测技术在乳腺癌早期筛查、肿瘤反应监测、微小残留病灶检测及治疗耐药性评估方面的最新发展动态,并剖析其在临床实践中面临的挑战与未来潜力。

基于混合方法研究的社区卫生服务中心开展乳腺癌筛查焦点问题分析

背景社区卫生服务中心是负责乳腺癌初筛的主要“阵地”,在其开展乳腺癌筛查过程中常受到许多因素制约,筛查效果难以保证。目的分析乳腺癌筛查项目在真实世界的焦点问题并探讨相应解决途径。方法采用混合方法研究的聚敛式设计,收集定量与定性数据。定量研究探究现场运行存在的问题:采用典型抽样法,于2021年4月—2022年11月在天津市4个区各选取1家社区卫生服务中心作为调查机构;采用偶遇抽样法,选取4家机构周围3 km内适龄女性作为居民调查对象。定性研究采用目的抽样法,于2022年6—11月对天津市9个区的9名受筛居民、12名参筛医生及4名分管领导进行半结构化访谈,运用扎根理论分析访谈内容,绘制乳腺癌筛查焦点问题扎根理论框架图。结合文献、典型调查数据进行混合方法研究,确定乳腺癌筛查的焦点问题。结果定量研究结果:在宣传工作中,机构宣传方式传统,居民的知晓率、参与率分别为46.3%(143/309)、32.4%(100/309);在筛查工作中,机构投入人力、物力不尽相同,筛查居民平均等待时长占总时长62.2%(40.5/65.1);在随访转诊工作中,人力物力投入少,居民钼靶转诊依从性为29.9%(59/197)。定性研究结果:访谈内容共形成38个综合开放式编码并汇聚为10个主轴编码和3个核心编码(宣传组织、筛查组织和随访转诊)。混合研究结果:最终确定3个焦点问题,即“如何提高居民参与率”“如何确保筛查机构人力和物力充足”“如何提高居民钼靶转诊依从性”。结论乳腺癌筛查效果受宣传组织、筛查组织及随访转诊三方面共同影响。为保证乳腺癌筛查取得实质性进展,优化乳腺癌筛查效果,需合理分配资源,确保筛查机构人力和物力充足;创新宣传方式,扩大宣传覆盖面,提升居民健康素养,提高参与率和钼靶转诊依从性。

Socioeconomic inequalities in cancer incidence and mortality:An analysis of GLOBOCAN 2022

Background:Given the recent updates in cancer burden estimates by GLOBOCAN 2022,this study was undertaken to provide pertinent perspectives within the context of the Human Development Index(HDI)and major world economies.Methods:Datasets sourced from GLOBOCAN encompassed cancer cases and deaths across all cancer types in 2022,alongside projections up to 2050.Cancer incidences and deaths of the top 10 cancers within China and four distinct HDI-classified regions were compared using descriptive analyses.Age-standardized incidence rates(ASIRs)and mortality rates(ASMRs)worldwide for the most prevalent cancers in 2022 across ten largest economies and four-tier HDIs were examined.The top five cancer types concerning both incidence and mortality in China were delineated by sex and age group.Results:In males,prostate cancer predominated in countries with low,high(except China),and very high HDI.Prostate and liver cancers were prominent causes of death in countries with low HDI.In females,breast and cervical cancers predominated in countries with low-to-medium HDI.Lung and colorectal cancer incidence and deaths increased with high HDI for both sexes.ASIRs and ASMRs for breast,prostate,lung,and colorectal cancers in the top 10 economies were higher than the global average.However,liver,stomach,and cervical cancers in most Western countries exhibited lower rates.In China,hematologic malignancies(43%)were prevalent among children aged 0-14 years,whereas thyroid cancer led among adolescents and young adults aged 15-39 years.Regarding incidence and mortality,lung cancer predominated for individuals over 40 years,except for females aged 40-59 years,in whom breast cancer predominated.Projected trends indicated substantial increases in new cancer cases(76.6%)and deaths(89.7%)over the next three decades.Conclusions:Infection-and poverty-related cancer burdens are offset by increased prostate,breast,colorectal,and lung cancer incidence associated with rapid societal and economic transitions.Cancer incidence and mortality patterns in China feature characteristics of developed and developing countries,necessitating tailored,evidence-based,and comprehensive strategies for effective cancer prevention and control.

改良根治术与保乳手术治疗早期乳腺癌患者的临床效果对比

目的对比改良根治术与保乳手术治疗早期乳腺癌患者的临床效果。方法将110例早期乳腺癌患者随机分为对照组(n=55)和观察组(n=55)。对照组采用改良根治术治疗,观察组采用保乳手术治疗,比较两组患者的手术相关指标、并发症发生情况及远期预后情况。结果观察组手术时间和住院时间均短于对照组,术中出血量少于对照组(P<0.05)。观察组并发症发生率为7.27%,明显低于对照组的23.64%(P<0.05)。术后2年,两组局部复发率(7.27%vs.3.64%)及远处转移率(3.64%vs.1.82%)比较,差异无统计学意义(P>0.05)。结论早期乳腺癌患者采用改良根治术与保乳手术治疗的远期预后相当,但保乳手术可明显缩短患者手术时间、住院时间,减少患者术中出血量,降低并发症发生率。

超声S-Detect技术联合乳腺简化MRI对早期乳腺癌的诊断效能

目的 探讨超声S-Detect技术联合乳腺简化MRI对早期乳腺癌诊断效能的分析。方法 选取2020年1月至2021年12月进行乳腺超声和MRI检查的85个病灶。患者年龄>14岁,且未进行手术及新辅助化疗治疗,肿瘤病灶直径≤2 cm,并进行穿刺或手术获得病理结果。以乳腺穿刺肿瘤病理结果为金标准,评估超声S-Detect技术、乳腺简化MRI及二者联合检查的诊断效能。结果 S-Detect、简化MRI及两者联合诊断的灵敏度分别为:69.5%,81.4%,98.3%,特异度分别为:88.5%,80.8%,76.9%,准确率分别为:75.3%,81.2%,91.8%,与病理一致性检验Kappa值分别为:0.50,0.58,0.80,AUC分别为:0.79,0.81,0.88。差异均有统计学意义(Z=1.979,P<0.05;Z=2.096,P<0.05)。结论 超声S-Detect与乳腺简化MRI技术联合对早期乳腺癌检查的灵敏度、准确率以及与病理一致性比单独使用S-Detect技术或简化MRI高,具有较高的诊断效能,可以对早期乳腺癌的早发现早治疗起到积极作用并为临床科室制定治疗方案提供有效帮助。

基层医疗卫生机构开展乳腺癌筛查能力评价指标体系构建研究

背景基层医疗卫生机构在开展乳腺癌筛查过程中受到许多因素制约,难以保证筛查工作取得实质性进展,因此建立一套科学、有效的基层医疗卫生机构开展乳腺癌筛查能力评价指标体系尤为重要。目的构建基层医疗卫生机构开展乳腺癌筛查能力评价指标体系。方法于2022年9—10月,通过文献检索和小组讨论初步拟定基层医疗卫生机构开展乳腺癌筛查能力评价指标体系库并设计专家函询表,于2022年11—12月采用目的抽样法邀请21名专家作为函询对象,根据函询结果计算专家积极系数、专家权威系数和专家协调系数,经过小组讨论最终确定指标体系,应用层次分析法确定各级指标权重系数并检验各级指标逻辑一致性。结果专家咨询表全部收回且有效,专家积极系数为100.0%,专家权威系数为0.812,重要性专家协调系数为0.209(P<0.001),最终确立的指标体系由结构、过程、结果3个一级指标,10个二级指标和56个三级指标构成,3个一级指标的权重分别为0.3108、0.1958和0.4934,各层级指标的一致性比率均<0.100。结论初步构建的基层医疗卫生机构开展乳腺癌筛查能力评价指标体系具有较高的权威性和科学性,有望为乳腺癌筛查能力评估相关研究提供指导与参考,指标体系的适用性和应用效果仍有待进一步验证。

乳腺癌术后淋巴水肿的早期识别与干预策略

目的探讨早期识别和干预对乳腺癌术后肢淋巴水肿的效果。方法选取80例乳腺癌术后患者为研究对象,按照随机数字表法分为观察组40例和对照组40例。对照组接受常规护理,观察组接受早期淋巴水肿识别和干预策略,比较2组患者术后6个月淋巴水肿发生情况以及患者的自感症状(采用BCLE-SEI评分进行评估,包括功能、社交、睡眠、性生活、情绪和归属感6个维度)。结果观察组患者术后6个月淋巴水肿发生率明显低于对照组(P<0.05)。观察组患者术后6个月BCLE-SEI评分在功能、社交及情绪维度得分优于对照组(均P<0.05);而在睡眠、性生活和归属感维度得分均为0。结论早期识别和干预可显著降低乳腺癌术后淋巴水肿的发生率,并有助于提高患者的生活质量。

血清肿瘤标志物联合检测在乳腺癌早期中的诊断效能分析

目的探究血清肿瘤标志物联合检测在乳腺癌早期中的诊断效能。方法目的选取2022年8月—2023年8月江苏大学附属武进医院收治的187例疑似乳腺癌患者作为研究对象,所有患者接受血清标志物糖类抗原153(Carcinoembryonic Antigen 153,CA153)、糖类抗原125(Cancer Antigen 125,CA125)、癌胚抗原(Car-cinoembryonic Antigen,CEA)联合检测,以病理学检查作为金标准,结合受试者工作特征(Receiver Operating Characteristic,ROC)曲线分析血清标志物联合检测诊断效能,通过Kappa值进行一致性分析。结果经金标准诊断,187例疑似乳腺癌患者中,155例确诊为乳腺癌,32例为良性乳腺疾病;血清标志物联合检测结果显示,154例为乳腺癌,33例为良性乳腺疾病。血清标志物联合检测的AUC为0.921,灵敏度96.77%,特异度87.50%。一致性分析结果显示,Kappa值为0.832。结论血清肿瘤标志物联合检测在保证安全、无创的同时,具有较高的诊断效能。

磁共振动态增强在早期乳腺癌影像诊断中的临床效果及检出率分析

目的 探讨磁共振动态增强(dynamic contrast enhanced magnetic resonance imaging,MRI-DCE)在早期乳腺癌影像诊断中的临床效果及检出率。方法 选择2022年1月—2023年8月在本院就诊的疑似乳腺癌患者86例为研究对象,并对所有的患者进行MRI-DCE、病理检查和超声检查,以病理检查为金标准,对以上各项检查方法的资料进行详细记录,评价MRI-DCE的诊断率。结果 经MRI-DCE的TCI分型,Ⅰ型、Ⅱ型、Ⅲ型的患者分别有41例(47.67%)、27例(31.40%)、18例(20.93%)。病理学检查显示早期乳腺癌、良性病变分别有56例、30例,超声检查分别为53例和33例,MRI-DCE分别为56例、30例,与病理学检查对照,MRI-DCE比超声更能显示出较好的诊断效果。超声检查和MRI-DCE检查的灵敏度分别为78.57%(44/56)、96.43%(54/56),特异度分别为70.00%(21/30)、93.33%(28/30),准确度分别为75.58%(65/86)、95.35%(82/86),MRI-DCE检查均高于超声检查(P<0.05)。超声检查和MRI-DCE检查的总满意度分别为84.88%、95.35%,MRI-DCE检查高于超声检查,差异有统计学意义(P<0.05)。结论 MRI-DCE作为一种先进的诊断技术,在乳腺癌的早期发现方面发挥了显著作用。该技术不仅显著提升了诊断的精确性,为临床治疗提供了有力的支持,还进一步提高了患者的满意度。因此,该技术值得在临床中广泛推广和应用。

The use of liquid biopsy in early breast cancer:clinical evidence and future perspectives

Liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is gaining momentum as a diagnostic modality adopted in the clinical management of breast cancer.Prospective studies testing several technologies demonstrated clinical validity and,in some cases,achieved the United States Food and Drug Administration approval.The initial testing and clinical application of liquid biopsy focused primarily on the diagnosis,while molecular characterization and monitoring of metastatic disease,with larger data from prospective studies,came in the last two decades.Although its role in metastatic setting is thus widely recognized,the current evidence does not provide support for the routine clinical use of liquid biopsy methods for the earlier stage of this disease.Considering the relevance of early detection,characterization,and management of breast cancer in the early-stage,this clinical setting is the most suitable to increase the chances for effective treatment selection and improved prognosis,and a better understanding of the main application of liquid biopsy tools in the earlier stage of breast cancer is therefore crucial.The aim of this review is to provide an overview of the clinical evidence and subsequent potential applications of liquid biopsy in early breast cancer,identifying the main existing caveats and the possible future scenarios.

Persistent EGFR/K-RAS/SIAH pathway activation drives chemo-resistance and early tumor relapse in triple-negative breast cancer

Triple-negative breast cancer(TNBC)is the most aggressive breast cancer subtype.It disproportionately affects BRCA mutation carriers and young women,especially African American(AA)women.Chemoresistant TNBC is a heterogeneous and molecularly unstable disease that challenges our ability to apply personalized therapies.With the approval of immune checkpoint blockade(ICB)for TNBC,the addition of pembrolizumab to systemic chemotherapy has become standard of care(SOC)in neoadjuvant systemic therapy(NST)for high-risk early-stage TNBC.Pembrolizumab plus chemotherapy significantly increased the pathologic complete response(pCR)and improved event-free survival in TNBC.However,clinical uncertainties remain because similarly treated TNBC partial responders with comparable tumor responses to neoadjuvant therapy often experience disparate clinical outcomes.Current methods fall short in accurately predicting which high-risk patients will develop chemo-resistance and tumor relapse.Therefore,novel treatment strategies and innovative new research initiatives are needed.We propose that the EGFR-K-RAS-SIAH pathway activation is a major tumor driver in chemoresistant TNBC.Persistent high expression of SIAH in residual tumors following NACT/NST reflects that the EGFR/K-RAS pathway remains activated(ON),indicating an ineffective response to treatment.These chemoresistant tumor clones persist in expressing SIAH(SIAH^(High/ON))and are linked to early tumor relapse and poorer prognosis.Conversely,the loss of SIAH expression(SIAH^(Low/OFF))in residual tumors post-NACT/NST reflects EGFR/K-RAS pathway inactivation(OFF),indicating effective therapy and chemo-sensitive tumor cells.SIAH^(Low/OFF) signal is linked to tumor remission and better prognosis post-NACT/NST.Therefore,SIAH is well-positioned to become a novel tumor-specific,therapy-responsive,and prognostic biomarker.Potentially,this new biomarker(SIAH^(High/ON))could be used to quantify therapy response,predict chemo-resistance,and identify those patients at the highest risk for tumor relapse and poor survival in TNBC.