EVALUATION OF PATIENT RADIATION DOSE EXPOSURE IN 4D-CT VERSUS 4D-CBCT FOR ADAPTIVE LUNG SBRT, ALIGNED WITH THE ALARA PRINCIPLE
Engy M. Abdelatif1, Shaaban Al-Assal2, Amr H. Hussein3, Ehab I. Mohamed4
1Ayady4040, Alexandria, Egypt; 2Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Alexandria University, Egypt; 3Cancer Management and Research Department, Medical Research Institute, Alexandria University, Alexandria, Egypt; 4Medical Biophysics Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Abstract
Introduction: It is important to an analytical assessment of the variations in patient radiation dose exposure associated with the use of 4D-CT versus 4D- CBCT in the implementation of adaptive Lung Stereotactic Body Radiation Therapy (SBRT), within the framework of adhering to the ALARA (As Low As Reasonably Achievable) principle in radiation safety practices.
Materials and Methods: This study involved 30 patients undergoing adaptive Lung SBRT, comparing two imaging radiotherapy scanning methodologies: the 4D-CT and 4D-CBCT, both of which were developed utilizing the Varian system using Real Positioning Management (RPM) system at Ayady4040 Hospital. We will be evaluating the Dose-Length Product (DLP) alongside the effective dose to scrutinize the influence of each technique on patient radiation dose exposure throughout the adaptive Lung SBRT treatment regimen. Comparative Analysis of Patient Radiation Dose Exposure between 4D-CT and 4D-CBCT in Adaptive Lung SBRT within the Framework of the ALARA Principle.
Results: The comparative analysis indicated that 4D-CBCT provided superior DLP value (213 ± 0.00) than 4D-CT (1477.93 ± 544.88) with a highly significant P value < 0.001, as well as 4D-CBCT provided superior effective dose value (2.98 ± 0.00) than 4D-CT (19.89 ± 5.88) with a highly significant P value < 0.001.
Conclusion: Strongly emphasizing the superior performance and efficiency of the 4D-CBCT over the 4D-CT in terms of radiation exposure and safety. Nevertheless, the image resolution provided by 4D-CT surpasses that of 4D- CBCT.
Keywords: lung cancer SBRT, 4D-CT, 4D-CBCT, Radiotherapy safety, ALARA, DLP, effective dose
MOLECULARLY INFORMED ONCOFERTILITY IN EARLY ENDOMETRIAL CANCER: THREE TERM LIVE BIRTHS AFTER CONSERVATIVE THERAPY IN POLE-ULTRAMUTATED ENDOMETRIOID ADENOCARCINOMA
Dauren Kaldybekov1,2, Dilyara Kaidarova2, Yerlan Kukubassov1, Alima Satanova1, Madina Orazgaliyeva1, Elzira Iskakova1
1Kazakh Research Institute of Oncology and Radiology, Almaty, Kazakhstan; 2Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
Background: Fertility-sparing treatment (FST) is increasingly offered to selected patients with presumed low-risk endometrial cancer (EC), yet relapse risk and optimal selection remain concerns. The TCGA-based molecular classification (POLEmut, MMRd, p53abn, NSMP) provides biologically grounded risk stratification, with POLE-ultramutated EC typically associated with an excellent prognosis. We report outcomes of a molecularly guided oncofertility pathway in women with POLE-mutated, endometrioid EC treated conservatively at the Kazakh Research Institute of Oncology and Radiology (KazIOR), Kazakhstan.
Methods: Three married women of reproductive age with type 1 endometrioid adenocarcinoma (G1–G2), clinically stage IA, underwent centralized pathology review. Molecular profiling included next-generation sequencing (Illumina comprehensive panel) and immunohistochemistry for mismatch repair (MMR) proteins and p53. All tumors demonstrated POLE mutation, retained MMR (pMMR), and p53 wild-type. Conservative management consisted of a levonorgestrel-releasing intrauterine system (LNG-IUS) for 3 months followed by 6 months of combined therapy with a GnRH agonist. Response was assessed with serial hysteroscopy and endometrial sampling within a multidisciplinary framework.
Results: Molecular profiling supported a favorable-risk phenotype in all cases (POLEmut/pMMR/p53 wild-type). All three patients achieved a sustained response enabling pregnancy and term delivery. Patient 1 delivered a healthy girl at 37+4 weeks (05 September 2022) and remains in long-term remission under active surveillance. Patient 2 delivered a healthy boy at 38 weeks (15 January 2023) and is currently in remission. Patient 3 delivered a healthy boy at 40+2 weeks (15 February 2025) and remains in remission. During follow-up, two patients developed benign endometrial hyperplasia and were managed with repeat LNG-IUS placement and continued close monitoring.
Conclusion: In early-stage endometrioid EC, incorporating molecular classification—particularly identification of POLE-ultramutated tumors—may refine candidate selection for FST and strengthen counseling regarding oncologic safety. A combined LNG-IUS plus GnRHagonist strategy within a structured, multidisciplinary oncofertility program resulted in three term live births with durable remission. Prospective studies should evaluate molecularly tailored algorithms to standardize selection, response assessment, and long-term surveillance.
Keywords: endometrial cancer; POLE mutation; molecular classification; fertility-sparing treatment; LNG-IUS; GnRH agonist; oncofertility.
TUMOR-INFLTRATING LYMPHOCYTES ARE MORE POWERFUL THAN T CELLS IN PBMCS IN CANCER PATIENTS
Alhamad BA
Blood and Cancer Department, King Abdullah International Medical Research Center (KAIMRC), Riyadh. Saudi Arabia
Introduction: The presence of tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment (TME) has long been recognized as a biomarker for predicting optimal chemotherapy response and improved survival. Recent advancements, however, have repositioned TILs as a crucial component of cancer immunotherapy. The detection of these T cells in the TME indicates their capacity to identify and target tumor cells, distinguishing them from T cells found in peripheral blood mononuclear cells (PBMCs).
Materials and methods: ELISA was used to measure the production of the human cytokines IL-2 and IFN-γ. The plate wells were quoted with capture antibodies specific to the target cytokines IL-2 and IFN-γ. Samples and standards were added to each well, and the plate was incubated to allow binding. Wells were washed to remove unbound substances. Next, detection antibodies were added, followed by substrate solution. Absorbance was measured using the VersaMax plate reader (Molecular Devices, USA) with 450 nm as the primary wavelength and 650 nm as the reference wavelength. Data were acquired using SoftMax Pro software (Molecular Devices, USA). A standard linear curve was generated using the average values.
Results: Using ELISA, higher levels of IL-2 and IFN-γ secretion were measured after co-culturing autologous TILs with tumor cells than after co-culturing autologous PBMCs with tumor cells. These results support the idea that TILs are more effective at identifying and attacking tumor cells than PBMCs.
Conclusion: This study underscores the significant role of TILs in cancer therapy, showing that they play a more vital role than T cells in PBMCs. It explains how TILs have historically been used as biomarkers to predict chemotherapy response and survival, but recent studies now view them as key players in targeting tumors. Therefore, by applying TIL therapy through the processes of isolation, expansion, and finally infusing the TILs back into cancer patients, we can avoid these obstacles and allow patients to benefit from the treatment.
UNDERDIAGNOSIS OF HIGH-GRADE CERVICAL LESIONS IN YOUNG WOMEN USING CYTOLOGY-BASED SCREENING: REAL-WORLD EVIDENCE FROM A MIDDLE-INCOME SETTING
Gaston Mendoza-De Lama1, Nancy Muñoz-Quispe1, Diana Díaz-Llontop1, Samantha Mendoza-Rivera1, Claudia Quiñones1, Richard Castillo-Laborio1, Renson Hidalgo1, Luis Taxa2
1Detecta Clinica, Lima, Peru. Full postal address: Av. Angamos Este 2688 – Surquillo, Lima, Peru; 2Universidad San Martín de Porres, Lima, Peru. Full postal address: Av. Alameda del Corregidor 1531, La Molina, Lima.
Introduction/Background: Despite global efforts to eliminate cervical cancer, cytology-based screening remains widely used in low- and middle-income countries. However, its diagnostic limitations—particularly in younger women—are insufficiently characterized in real-world settings.
Objectives: We aimed to evaluate the diagnostic accuracy of cervical cytology for detecting high-grade squamous intraepithelial lesions (HSIL+) and to quantify age-related patterns of underdiagnosis.
Methods: We conducted a retrospective cohort study including 155 women who underwent cervical cytology (reported according to the Bethesda System) followed by histopathologic confirmation via cervical biopsy. Cytology results were classified as negative/ASC-US/LSIL or HSIL/carcinoma. Histology was dichotomized as <HSIL (benign or CIN1) or HSIL+ (CIN2, CIN3, or carcinoma), serving as the reference standard. Diagnostic accuracy metrics were calculated, and concordance, overdiagnosis, and underdiagnosis were analyzed overall and stratified by age.
Results: Of the 155 women included, 18.7% (n=29) had histologically confirmed HSIL+. Cervical cytology demonstrated a sensitivity of 72.4%, specificity of 96.8%, positive predictive value of 84.0%, negative predictive value of 93.8%, and an overall diagnostic accuracy of 92.3%. Overall concordance between cytology and biopsy was 91.6%. However, age-stratified analysis revealed relevant disparities. Among women ⩽30 years, concordance decreased to 76.7%, and underdiagnosis was observed in 20.0% of HSIL+ cases, corresponding to six missed high-grade lesions in this subgroup. In contrast, concordance increased progressively with age, reaching 94.7% in women >45 years, with minimal underdiagnosis (1.8%). Overdiagnosis remained consistently low across all age groups (<4%).
Conclusions: Although cervical cytology maintains high specificity and overall accuracy, a substantial proportion of high-grade lesions are missed in young women. These findings highlight a critical vulnerability of cytology-based screening programs and underscore the need to strengthen cervical cancer prevention strategies in younger populations, particularly in settings where HPV-based screening is not yet universally implemented.
OVARIAN REPORTING AND DATA SYSTEM IN BORDERLINE EPITHELIAL VERSUS MALIGNANT OVARIAN TUMORS
Henidy SE1, Elsokkary HH1, Sheta E2, Eleba AA1.
1Gyneoncology unit in Shatby University hospital, Faculty of Medicine, Alexandria University; 2Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
Introduction: Borderline ovarian tumors (BT) are a distinct pathological entity. Their high incidence in reproductive age group highlightsthe critical need of fertility sparing management. Due to its overlapping clinical, laboratory and radiologic features with malignant cases, accurate preoperative diagnosis is challenging. Transvaginal ultrasound is the first-line imaging modality for adnexal masses; however, variability in interpretation may lead to inconsistent risk assessment. The Ovarian–Adnexal Reporting and Data System (O-RADS) was developed to standardize ultrasound reporting and improve diagnostic accuracy.
Aim of the work: To evaluate the diagnostic performance of the O-RADS ultrasound classification system in differentiating borderline from malignant ovarian tumors.
Patients and methods: This prospective observational analytical study included female patients presented with ovarian tumors in the gynecologic oncology unit at El-Shatby Maternity Hospital, Alexandria University, between November 2024 and October 2025. All patients underwent detailed clinical and laboratory assessments. Preoperative transvaginal ultrasound with assignment of an O-RADS category as well as color doppler assessment was done. O-RADS performance was evaluated against post operative histopathological results.
Results: Among the 63 included ovarian tumors, 25 (39.7%) were BT (17 (68%) serous, 7 (28%) mucinous and a single case (4%)seromuncinous) versus 38 (60.3%) were malignant (20 (52.6%) epithelial carcinomas, 10 (26.3%) germ cell tumors, single cases (0.2%) sex cord tumor and 6 (15.8) metastatic extraovarian carcinomas). BTs were categorized as O-RADS 4 in 68 % and O-RADS 5 in only 8%, whereas malignant tumors were categorized as O-RADS 5 in 71%. The difference in O-RADS category between the two groups was statistically significant (p < 0.001). ROC curve analysis showed that O-RADS category 5, is 84.2% sensitive 64% specific in differentiating malignant from borderline tumors. The positive and negative predictive values were 72.9 % and 78.6 % respectively. Solid morphology, internal papillary projections, thick septations, high internal vascular flow and color Doppler score (3–4) were significantly detected in malignant cases.
Conclusion: Integration of O-RADS into routine clinical practice canimprove preoperative diagnostic confidence and support individualized management of borderline ovarian tumors. Structured ultrasound assessment incorporating morphologic features and Doppler evaluation significantly enhances preoperative risk stratification.
1. LIQUID BIOPSY A NEW ERA IN ONCOLOGY DIAGNOSTICS AND MONITORING
*Abdullah Elsayed, Dhia Ahmed, Abdelrahman Fareed, Abdelrahman Rafet, Ahmed Mohammed
Introduction: Cancer is the second leading cause of death worldwide, with tissue biopsy (TBx) still the diagnostic gold standard, utilized when a tumor’s location is confirmed.
Recently, liquid biopsy (LBx) turns a blood draw into a means for therapy selection, MRD detection, resistance monitoring, and recurrence surveillance in solid tumors. Consequently, the key question of this study is whether LBx replaces or complements TBx.
Methods: A comprehensive review was conducted on Circulating Tumor DNA (ctDNA) in LBx technology using peer-reviewed studies and clinical trials on different types of tumors published between 2021 and 2025, retrieved from NEJM, Lancet and Nature journals. Technologies were conducted by one of the following methods: next generation sequencing (NGS), fragmentation methods and multimodal approaches.
Results: Multiple platforms exhibited diagnostic and clinical performance, including:
Cobas EGFR Mutation test v2 in advanced non-small cell lung cancer. NSCLC, showed a 76.7% sensitivity and 98.2% specificity, also Detecting MRD in Resectable Colorectal Cancer. showed high specificity (>98%) with sensitivity (95+%). Besides, ctDNA-positive patients had ~12-fold higher recurrence risk and ~9.7-fold higher mortality than ctDNA-negative. Furthermore Assessing tumor Heterogeneity, in NSCLC, adenocarcinoma (LUAD) and squamous carcinoma (LUSC) showed: Preoperative ctDNA detection: 97% in LUSC vs 19% in LUAD, with subclonal variants detected in ctDNA in ~68% of patients.
Meanwhile monitoring treatment response & resistance in breast cancer, showed: ctDNA clearance strongly correlated with radiographic response (p<0.001) and detected progression with ≈88% sensitivity. moreover, ctDNA detects changes in Resistance and recurrence ~3 months earlier than imaging
Conclusion: LBx enables noninvasive, repeatable, and rapid testing, while TBx remains essential for definitive diagnosis and classification. Despite advances, LBx faces challenges in sensitivity, specificity, cost, and standardization. No single biopsy method can yet capture the full complexity of tumor biology. Rather than choosing one over the other, integrating LBx and TBx may redefine the future of precision oncology
Keywords: Circulating tumor DNA (ctDNA), Liquid biopsy (LBx), Cancer recurrence monitoring, Minimal residual disease (MRD).
BREAST CANCER METASTASIS TO THE STOMACH: A RARE FORM OF PRESENTATION
S.BOUHAROUD . H.DJEDI
Medical Oncology Department; Annaba University Hospital ; Algeria Mail : safiahamici@hotmail.com
Breast cancer is among the most prevalent malignancies in women worldwide, with approximately 2.3 million new cases annually. Its metastatic behavior varies significantly depending on histological subtype and molecular characteristics. While ductal carcinoma commonly spreads to the lungs, bones, liver, and brain, lobular carcinoma shows a distinct affinity for the gastrointestinal tract, peritoneum, and retroperitoneum.
Gastric metastasis from breast cancer is rare (5–18% incidence), primarily linked to lobular carcinoma. Due to nonspecific gastrointestinal symptoms, diagnosis is often delayed or mistaken for primary gastric malignancies..
We describe a case of a 47-year-old woman who was admitted with anemia and stomach pain, An oesophagogastroduodenoscopy identified a mass in the stomach, and biopsies were consistent with upper gastrointestinal independent cell adenocarcinoma; However, a subsequent staging computational tomography showed a left breast lesion:ACR5, Biopsie: invasive lobular carcinoma, luminal A subtype and bone metastases.
Immunostaining of the gastric biopsies were consistent with a breast metastasis.(GATA3 Positif; oestrogen receptors ans progesterone receptors positifs; C-erbB2 negatif ;KI: 12%.
After discussion in the multidisciplinary team meeting, the patient receivedpalliative chemotherapy (docetaxel+cyclophosphamide) with denosumab and palliative radiotherapy for bone metastases. The evaluation after three months shows a marked regression of gastric mass and clinical improvement; the patient continues her treatment in our department.
This is a rare case of metastatic breast cancer presenting with gastrointestinal tract symptoms and highlights the importance of considering breast cancer as the primary origin for any gastric malignancy
Keywords: Breast Cancer, Gastric Metastasis, Case Report, endoscopy, Immunohistochemistry
QUALITY OF LIFE IN BREAST CANCER PATIENTS IN SAUDI ARABIA: A SYSTEMATIC REVIEW
Enar A. Almazroy2,3, Faisal F Aljadani2,3, Reem O. Nughays2,3,Ghaida E. Alharbi2,3, Shahad K.Elyas2,3, Hala E. Danish2,3,Rimaz T. Alanazi 3,4, Badr Aldrees1,2,3 Ghalia Jadkreem1,2,3 Zaher AMikwar1,2,3,5
1Surgical Oncology, Department of General Surgery, Ministry of the National Guard – Health; Affairs, Jeddah, Saudi Arabia; 2Arabia; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi; 3King Abdullah International Medical Research Center, Jeddah, Saudi Arabia; 4 College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 5 Section Head of Surgical Oncology, Department of General Surgery, Ministry of the National Guard – Health Affairs, Jeddah, Saudi Arabia
Paper aim: Breast cancer is the most prevalent malignancy worldwide which carries a high mortality rate. Quality of life (QoL) is adversely affected by the disease process; thus, this systematic review aimed to evaluate the QOL among women with breast cancer in Saudi Arabia, and descriptively analyze the risk factors that are associated with low QOL.
Method: Following the PRISMA guidelines for systematic review, a literature search for all cross-sectional studies conducted in Saudi Arabia was performed in five databases including Pubmed, DOAJ, Scopus, Google scholar, and Mendeley, then, the studies which met the eligibility criteria were extracted and assessed for quality using AXIS tool.
Results: Following a full-text evaluation, there were a total of 8 included articles. Based on the EORTC QLQ-C30 questionnaire, the Global Health Status (GHS) score of patients with breast cancer ranged from 31.2 +20 to 73.16 ± 20.26. Elements that impact HRQoL are the age of breast cancer diagnosis, marital status, and number of children. Women who are childless, widowed, or divorced have lower quality of life (QoL), and those who were diagnosed beyond the age of 50 have a worse emotional functioning. Emotional well-being is lowered by the coexisting medical issues especially if living alone. Chemotherapy and monoclonal antibodies can make the patients stressed and more tired.
Rehabilitation groups surprisingly can increase insomnia, while immunotherapy and radiation therapy may decrease physical function, particularly in older patients Conclusion:This systematic review has identified several factors that affect the quality of life of breast cancer patients in Saudi Arabia, including physical, mental, functional, and social well-being, as well as various sociodemographic factors. By understanding these factors and implementing a QoL assessment tool within a clinical setting can aid in the development of supportive measurements for those patients and their families, helping them to manage their life challenges more effective
BREAST CANCER IN NORTHWEST TUNISIA: INSIGHTS INTO EPIDEMIOLOGICAL, CLINICAL, AND HISTOPATHOLOGICAL PROFILES IN THE SILIANA REGION
Jouini Safa1 ; Rekik Wafa2 ; Zribi Riadh 1 et Berrich Ali1.
1Department of Surgery, Regional Hospital of Siliana;Tunisia; 2Department of Pathology; Regional hospital of Siliana; Tunisia
Introduction: Breast cancer is the most common cancer among Tunisian women and worldwide. In the Siliana region, northwest Tunisia, the clinicopathological and evolutionary features of this cancer have not been established in previous studies. Knowledge of these features is essential for culturally adapted prevention strategies and healthcare planning in the region.
Aim: The aim of our study was to establish a clinical and pathological profile of patients treated at the only public surgical oncology unit in the Siliana region.
Methods: We conducted a retrospective descriptive study of 83 patients diagnosed with breast cancer over a two-year period, from July 2023 to July 2025.
Results: Among patients treated in the surgical oncology unit of Siliana Regional Hospital for invasive breast carcinoma, the mean age was 52 years (range: 25–92 years). The median delay between the onset of symptoms and consultation was 6 months, ranging from 1 month to 3 years. Locally advanced cancer was observed in 21 patients, while metastatic disease at diagnosis was found in 5 patients. Invasive ductal carcinoma was the most frequent histological type (77.6%). The most prevalent histological grade was SBR II. Histological lymph node involvement was observed in 62.7% of cases. Lymphovascular invasion and perineural invasion were detected in 23.7% and 23.6% of cases, respectively. The most common molecular subtype was Luminal B. All cases were discussed in multidisciplinary team meetings. After a median follow-up of 24 months, only two patients experienced locoregional or distant relapse.
Conclusion: Breast cancer in our population is characterized by relatively young age at diagnosis, large tumor size, and a high frequency of poor histopathological factors. These findings highlight the need to develop effective programs for the early detection and prevention of breast cancer in the region. The implementation of a national mass screening strategy is essential to reduce breast cancer-related morbidity and mortality.
BRCA1 AND BRCA2 GENE HETEROGENITY IN OVARIANCARCINOMA AND POLYNEOPLASIA
Savanevich AL
Department of Obstetrics and Gynecology, Grodno State Medical University, Grodno, Republic of Belarus
Introduction: Polyneoplasia is a significant challenge in modern medicine. Ovarian carcinoma is often associated with hereditary cancer forms caused by germline mutations in the BRCA1 and BRCA2 genes. Studying the spectrum of BRCA mutations in patients with ovarian carcinoma and polyneoplasia is particularly relevant for understanding carcinogenesis mechanisms and developing prevention strategies.
Material and Methods: The study included 82 patients of Slavic origin from the Grodno region with ovarian carcinoma and polyneoplasia. Data from medical records, questionnaires, and classical criteria for primary multiple tumors were used. Venous blood was used for molecular genetic analysis. DNA was extracted using standard methods. The BRCA1 mutations c.5266dupC and c.4035delA were identified using allele-specific PCR. Negative samples were further analyzed using NGS sequencing on an Illumina NextSeq 500 platform. Bioinformatic data processing was performed according to GATK Best Practice guidelines.
Results: Pathogenic mutations in the BRCA1 and BRCA2 genes were identified in 45 out of 82 patients (55%). Mutations in the BRCA1 gene predominated (87%). The most frequent were founder mutations: c.5266dupC and c.4035delA. The average age of ovarian carcinoma diagnosis in carriers of c.5266dupC was 47,8 years, and in carriers of c.4035delA, it was 57,1 years. Ovarian carcinoma most frequently co-occurred with breast cancer (54%), less often with endometrial cancer (26%), and colorectal cancer (12%). A pronounced "founder effect" was detected in 71% of mutation carriers. Family history of cancer was burdened in 74% of BRCA1 mutation carriers. Cases of familial cancer were also noted in patients without BRCA mutations, indicating the need for multigene testing. The results underscore the importance of implementing simple and affordable PCR tests for detecting common mutations at the regional level, as well as using NGS for more complex cases.
Conclusion: This study demonstrates a high frequency of founder mutations in the BRCA genes among women with ovarian carcinoma and polyneoplasia in the Belarusian population. The obtained data justify the need to develop personalized monitoring and prevention programs for patients with a hereditary predisposition to cancer.
CLINICAL UPDATE: CUTTING-EDGE ADVANCES IN BREAST CANCER MANAGEMENT AND PERSONALIZED SCREENING
Alalawneh JE1, Alalawneh MM2
1Department of Allied Medical Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
Introduction: Breast cancer management is undergoing a fundamental transition toward precision-driven care integrating molecular therapeutics with individualized screening strategies. Advances reported during 2024–2025 have accelerated the clinical adoption of antibody–drug conjugates, next-generation endocrine agents, and artificial intelligence–assisted imaging. Collectively, these innovations aim to improve survival outcomes, reduce overtreatment, and refine risk-adapted decision-making across disease stages.
Materials and Methods: This clinical update is based on a structured narrative synthesis of peer-reviewed phase III clinical trials, international oncology congress reports, and validated screening studies published between January 2024 and late 2025. Emphasis was placed on pivotal therapeutic trials evaluating novel targeted and immunotherapeutic agents, as well as studies assessing AI-enhanced mammography and established multivariable risk-stratification models. Evidence was reviewed analytically without generating new datasets or reporting original patient-level information.
Results: Recent therapeutic advances have redefined standards of care across major breast cancer subtypes. In HER2-positive metastatic disease, next-generation antibody–drug conjugate–based regimens demonstrated superior progression-free survival compared with earlier HER2-directed standards, supporting their use in earlier treatment lines. In hormone receptor–positive, HER2-negative breast cancer, selective estrogen receptor degraders delayed endocrine resistance linked to ESR1 alterations, prolonging clinical benefit in appropriately selected patients.
In triple-negative breast cancer, combination strategies integrating immune checkpoint inhibitors with targeted cytotoxic conjugates achieved clinically meaningful improvements in objective response and disease control in biomarker-defined populations.
Parallel progress in early detection reinforced the role of personalized screening. AI-assisted mammography improved diagnostic specificity, while individualized risk models incorporating breast density and genetic risk factors enabled more accurate stratification and reduced interval cancer rates in high-risk groups, without increasing unnecessary biopsies.
Conclusions: The current evidence base confirms that the integration of genomically guided systemic therapy with AI-augmented screening is central to contemporary breast oncology. These approaches support precision de-escalation in early-stage disease and expanded therapeutic benefit in advanced settings. Effective implementation, particularly in resource-limited environments, requires strategic investment in genomic testing, validated AI tools, and multidisciplinary training to translate global innovation into sustainable clinical practice.
NARRATIVE REVIEW: EVOLUTION OF PRECISION MEDICINE IN BREAST ONCOLOGY
Abouodeh SM1
1Faculty of Medicine, Palestine Polytechnic University, Hebron, Palestine
Introduction: Precision medicine has fundamentally reshaped breast oncology over the past two decades, evolving from single biomarker targeting to complex, adaptive strategies integrating genomics, transcriptomics, and artificial intelligence. This trajectory reflects growing recognition of breast cancer heterogeneity, mechanisms of therapeutic resistance, and the need for individualized treatment and screening approaches across diverse populations. This review aims to map key therapeutic and technological milestones in precision breast oncology and to outline future implementation priorities in diverse healthcare settings.
Materials and Methods: This narrative review synthesizes landmark phase III clinical trials, translational research, and contemporary multi-omics studies published up to 2025. Key therapeutic milestones—from early HER2-directed therapies to next-generation antibody–drug conjugates, endocrine resistance modulators, and AI-driven risk stratification—are integrated with emerging biological insights. Evidence is discussed conceptually without presentation of original patient-level data.
Results: The precision medicine paradigm in breast oncology has progressed through distinct yet interconnected phases. HER2-targeted therapy advanced from monoclonal antibodies to highly potent antibody–drug conjugates, extending benefit to tumors with low HER2 expression. In hormone receptor–positive disease, CDK4/6 inhibitors transformed first-line management, while subsequent identification of ESR1-mediated resistance prompted development of next-generation endocrine agents capable of restoring sensitivity.
Triple-negative breast cancer, historically limited to chemotherapy, has benefited from biomarker-guided immunotherapy and targeted conjugates, improving response rates in selected populations. More recently, integrative multi-omics analyses have uncovered novel molecular subtypes and actionable vulnerabilities, enabling rational therapeutic combinations and dynamic treatment adaptation. Circulating tumor DNA–guided strategies and AI-enhanced risk models further support earlier intervention, treatment switching, and personalized screening, particularly in patients with dense breast tissue or hereditary risk profiles.
Conclusions: The evolution of precision medicine in breast oncology reflects a shift from static, single-target interventions toward flexible, data-driven ecosystems that adapt to tumor biology over time. Integration of multi-omics profiling, liquid biopsy technologies, and artificial intelligence offers a scalable framework to optimize outcomes while minimizing overtreatment. Strategic implementation of cost-effective precision tools may facilitate broader adoption in resource-limited settings, supporting equitable advances in breast cancer care.
SPATIAL COMPARISON AND PROGNOSTIC SIGNIFICANCE OF MACROPHAGES IN PRIMARY COLORECTAL CANCER AND LIVER METASTASES
Esraa Ali EA1, Lenka Červenková LC2, Filip Ambrozkiewicz FA1, Václav Liška VL2, Kari Hemminki KH1,3, Andriy Trailin AT1
1Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, 32300 Pilsen, Czech Republic; 2Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, 32300 Pilsen, Czech Republic; 3Department of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Introduction: Biomarker-guided systemic therapies have improved overall survival (OS) in patients with colorectal cancer liver metastases (CLM). Tumor-associated macrophages (TAMs) are key players in tumor initiation, progression and metastasis. Investigating the spatial distribution and prognostic significance of distinct TAM subsets in primary colorectal cancer (pCRC), as well as in synchronous and metachronous liver metastases (LM), may provide deeper insights into the immunological mechanisms driving these different metastatic settings and help guide more effective therapies.
Material and Methods: Tissue samples included 55 paired pCRC and synchronous LM and 44 pairs of pCRC and metachronous LM. After immunohistochemical staining for macrophage markers: M0 (CD68), M1 (CD80), M2 (CD163 and CD206), whole-slide analysis was performed using the QuPath software in tumor center, inner margin (IM), outer margin (OM) and peritumoral (PT) regions of both pCRC and LM. TAM densities and M1/M2 ratios in pCRC and LM were evaluated as prognostic variables for overall survival (OS) after liver surgery in both groups, and for time to LM (TLM) in patients with metachronous LM.
Results: CD163+ cells exhibited the greatest densities whereas CD80+ cells were the least abundant across both groups and all regions of interest (ROI) in both pCRC and LM. LM showed greater CD163+ and lower CD80+ cell densities in various ROI than pCRC (P < 0.05 for each comparison). In patients with metachronous LM, high densities of CD80+ cells in OM of pCRC correlated with shorter TLM but longer OS. In the synchronous group, a higher CD80/CD206 ratio in the PT of pCRC was associated with shorter OS. Conversely, a higher CD80/CD163 ratio in PT of LM was associated with longer OS.
Conclusions: The predominance of immunosuppressive CD163+ M2 macrophages in LM, coupled with low CD80+ M1 macrophages, may contribute to poor outcomes in patients with CLM. While M1 macrophages can prolong OS through tumoricidal activity, they may also accelerate metastasis by selecting more malignant, resistant tumor clones. The prognostic significance of the M1/M2 ratio varies by M2 subtype, underscoring the complexity of TAM polarization and its clinical relevance in metastatic CRC.
IMPACT OF NEOADJUVANT CHEMOIMMUNOTHERAPY (NACI) ON PATHOLOGICAL COMPLETE RESPONSE (PCR) AMONG PATIENTS WITH METAPLASTIC TRIPLE NEGATIVE BREAST CANCER (TNBC)
Kai CC Johnson1; Julie Stephens2; Kendra Burgei3; Robert Wesolowski1; Sachin R Jhawar1; Samilia Obeng-Gyasi1; Daniel Stover1; Brandon Slover2; Yevgeniya Gokun2; Margaret Gatti-Mays1.
1The Ohio State University – James Comprehensive Cancer Center, Columbus, OH, USA; 2The Ohio State University – Center for Biostatistics, Columbus, OH, USA; 3The Ohio State University – College of Medicine, Columbus, OH, USA
Background: Metaplastic breast cancer is an aggressive histologic subtype commonly classified as triple negative breast cancer (TNBC) with inherent resistance to neoadjuvant chemotherapy (NAC). However, the use of neoadjuvant chemoimmunotherapy (NACI) has shown promise in improving rates of pathologic complete response (pCR) in TNBC. We aim to examine real world data with a specific focus on metaplastic TNBC.
Material & Methods: Using the National Cancer Database, we examined patients diagnosed between 2018 to 2022 with stage 2-3 TNBC who received either NAC or NACI followed by curative breast surgery. Our primary objective compared pCR, defined as ypT0/is ypN0 based on AJCC 8th edition, following NACI between metaplastic and non-metaplastic TNBC. We alsocompared pCR for metaplastic TNBC by receipt of NAC versus NACI and overall survival (OS) by pCR and histology type. Log-rank tests compared Kaplan-Meier curves (OS) and Chi-square tests compared pCR.
Results: A total of 38,480 non-metaplastic TNBC and 834 metaplastic TNBC cases were identified. Following NACI, only 20.7% of metaplastic TNBC patients achieved pCR versus 49.7% of non-metaplastic TNBC patients (p<0.001). Among metaplastic TNBC patients, pCR was significantly higher with NACI (21.8%) versus NAC (14.8%) (p=0.014). No difference in OS was found with metaplastic TNBC that achieved pCR by NAC vs NACI (p=0.279), though event rates were very low in both arms. Similarly, in those who achieved pCR, no difference in OS was found in between metaplastic versus non-metaplastic cases (p=0.964). However, residual metaplastic TNBC carried a significantly worsened OS compared to residual non-metaplastic TNBC (p<0.001). The 4-year OS was 67.5% versus 74.9%, respectively.
Conclusions: The use of immunotherapy in the management of metaplastic TNBC was shown to meaningfully improve pCRrates among this aggressive breast cancer subtype. Conversely, while OS was similar among metaplastic and non-metaplastic patients who achieved pCR, worsened survival was seen for those with residual metaplastic TNBC versus residual non-metaplastic TNBC. Further steps are necessary to improve the ways we escalate adjuvant therapies for those with residual metaplastic TNBC.
