Background Triple-negative breast cancer (TNBC) is one of the most aggressive and highly metastatic subtypes of breast cancer. It lacks canonical biomarkers and is often resistant to treatments, including radiotherapy (RT). This mandates the development of better treatments through identifying novel therapeutic targets and biomarkers in TNBC to improve patient stratification for treatment and facilitate novel drug development. We have previously shown that anticancer effects of RT are synergized by the inhibition of polo-like kinase 4 (PLK4) by CFI-400945. Objectives, Design and Methods In the present study, we aimed to obtain mechanistic insights of the anticancer effects of RT in combination with CFI-400945 using bulk RNA-sequencing in MDA-MB-231 TNBC cells treated with single agents and their combination. Results Differential gene expression (DEG) and pathway enrichment analyses of the bulk transcriptomics data have identified perturbations in immune and senescence related genes and pathways in TNBC cells treated with RT alone or in combination with CFI-400945. Validation of the identified DEGs showed significant upregulation of ICAM - 1 (Intercellular Adhesion Molecule-1) both at transcript and protein levels following combination treatment compared to untreated control cells. This was accompanied by activation of STAT3 protein and increased cellular senescence determined by β-galactosidase assay in combination treatment compared to untreated control. Conclusion Overall, our data suggest that ICAM-1 and STAT3 signaling axis may play an important role in TNBC cell response to RT and PLK4 inhibition.
Breast cancer remains the most frequently diagnosed cancer and a leading cause of cancer-related mortality among women worldwide, underscoring the need for accurate, minimally invasive biomarkers to support precision oncology. Conventional tissue biopsy remains the standard for molecular characterization but is limited by its invasiveness, inability to capture spatial and temporal tumor heterogeneity, and challenges in serial monitoring. Circulating tumor DNA (ctDNA), a tumor-derived fraction of cell-free DNA, has emerged as a promising liquid biopsy biomarker capable of providing real-time genomic information throughout disease progression. This narrative review examines recent advances in ctDNA biology, analytical technologies, clinical applications, current limitations, and future directions in breast cancer management. A structured literature search of PubMed/MEDLINE, Scopus, Embase, Web of Science, and Google Scholar identified relevant English-language publications from 2015 to 2026. Current evidence indicates that highly sensitive platforms, including digital PCR, BEAMing, and next-generation sequencing, can detect clinically actionable alterations in genes such as PIK3CA , ESR1 , TP53 , ERBB2 , AKT1 , and BRCA1/2 . ctDNA has demonstrated particular utility in identifying minimal residual disease, monitoring therapeutic response, detecting emerging resistance mechanisms, and guiding targeted treatment selection in advanced breast cancer. However, applications in early cancer detection, population screening, and artificial intelligence-assisted clinical decision-making remain investigational. Widespread clinical implementation is constrained by low ctDNA abundance in early-stage disease, analytical variability, limited assay standardization, and cost considerations. Continued technological innovation, prospective multicenter validation, standardized testing protocols, and evidence-based clinical guidelines are essential to fully integrate ctDNA into routine precision breast cancer care.
Background Breast cancer (BC) is a complex disease characterized by various demographic and clinicopathological factors. Understanding the prevalence and interrelationships of these factors across regions is essential for clarifying disease progression, improving prevention and early detection strategies. Design This retrospective cohort study included 4043 female breast cancer patients treated at a radiotherapy & oncology center in northeastern Iran. Due to complete-case analysis, sample sizes varied across analyses. Objectives To describe the frequency of demographic and selected clinicopathological characteristics and to investigate their interrelationships. Methods Data preprocessing was performed to ensure accurate and effective presentation of the results. Univariate log-linear analyses were first conducted to assess crude associations between variables. Variables of interest were then entered into a multivariable log-linear model adjusted for potential confounders, including age at diagnosis, estrogen receptor (ER) status, and progesterone receptor (PR) status. Results Patients residing in rural areas showed a significant associationwith a time to presentation longer than five months (OR = 1.48, 95% CI = 1.12–1.96), additionally educated patients significantly associated with shorter time to presentation (OR = 0.69, 95% CI = 0.58–0.83). No significant association was observed between age at diagnosis and time to presentation. Likewise, no association was found with various statuses for HR/HER2, or grade and time to presentation. Education, employment, place of residence and marital status showed no statistically significant associations with clinicopathological characteristics. Any observed association in unadjusted models could be explained by age at diagnosis, ER status, or time to presentation. Multiple tumors were associated with higher odds of ER/PR positivity (OR = 1.42, 95%CI = 1.01-1.99) and were negatively associated with age 40–60 compared to those under 40 (OR = 0.64, 95%CI = 0.44-0.93). Tumor laterality showed no statistically significant relationships with hormone receptor (HR) status, histological grade, employment, education, place of residence, or marital status. Conclusion This study identified associations between several variables. However, the observed associations may be influenced by unmeasured factors. Further studies are needed to clarify the underlying mechanisms driving these relationships.
Background Globally, breast cancer mortality is rising particularly in transitioning countries where it is exacerbated by late diagnosis and poor diagnostic infrastructure. The dearth of data on the biology of breast tumours from under-studied populations compromise management of breast cancer patients resulting in poor patient outcomes. We conducted a study to determine the prevalence and impact of Claudin-low and CK8/18 in the Botswana female breast cancer cohort. Design This laboratory experimentally retrospective cross-sectional study was carried out on archived formalin-fixed paraffin embedded (FFPE) tissue obtained from mastectomy specimens. Objectives To determine the protein expression of CK8/18 and Claudin-3, Claudin-4 and Claudin-7 on breast mastectomies from Botswana female breast cancer cohort. Methods CK8/18, Claudin 3, Claudin 4 and Claudin 7 were Immunohistochemical determined on 125 previously molecular classified Botswana female mastectomies. Statistical software STATA and SPSS were used to determine the relationship between CK8/18 & Claudin expression, clinicopathological variables, breast cancer molecular subtypes, CK5/6 and EGFR. Results The prevalence of Claudin-low tumours in our cohort was 22% (27/125) had a significant relationship with histological subtype, p=0.002. Claudin 3 and Claudin 4 were highly expressed in 54% (67/125) and 53% (66/125) of breast tumours respectively. Claudin 3 and claudin 4 significantly correlated with molecular breast cancer subtypes, p= 0.001. Claudin 7 was expressed in 47% (59/125) of all breast tumours and had a significant relationship with CK5/6, p=0.029. CK8/18 was highly expressed by 64% (80/125) of mastectomies and correlates with; Tumour grade (p= 0.005) and breast cancer molecular subtypes (p=0.002). Conclusion Diagnostic stratification of breast tumours should include Claudin-low tumours as they respond differently to therapy when compared to the intrinsic breast cancer molecular subtypes. There is also a significant CK8/18 signaling that warrants deployment of anti-CK8/18 antagonists where ER is poorly expressed.
Robotic assisted nipple sparing mastectomy (RNSM) has been increasingly adopted for therapeutic breast cancer surgery. However, comparative evidence regarding oncologic outcomes and surgical safety relative to conventional open nipple sparing mastectomy (CNSM) remains limited. A systematic review was conducted in accordance with PRISMA 2020 guidelines. MEDLINE, Embase, Scopus, Web of Science, and Cochrane CENTRAL were searched for studies reporting outcomes of RNSM and/or CNSM with implant based reconstruction for invasive breast cancer or ductal carcinoma in situ. Both comparative studies and single arm robotic series were included. Prophylactic mastectomies were excluded. Primary outcomes were locoregional recurrence and disease free survival (DFS). Clinical characteristics, follow up duration, and surgical complications were descriptively summarized. Of 63 identified studies, 7 met inclusion criteria, comprising comparative cohorts and single arm robotic series. Patients were predominantly middle aged, with early stage disease, small tumor size, hormone receptor positive tumors, and low prevalence of smoking and major comorbidities. Median or mean follow up ranged from approximately 6 to 36 months. Compared with CNSM, RNSM was associated with longer operative time but lower intraoperative blood loss. Overall complication rates ranged from 0% to approximately 30%, with infrequent major complications. Rates of nipple areolar complex necrosis, skin necrosis, infection, seroma, hematoma, and implant loss were comparable between approaches. Locoregional recurrence was uncommon, ranging from 0% to approximately 2%, and no meaningful differences in DFS were observed across comparative studies. Single arm robotic series demonstrated similarly low recurrence rates and acceptable safety profiles during available follow up. This systematic review suggests that RNSM with implant based reconstruction provides oncologic and surgical outcomes comparable to CNSM in selected breast cancer patients. While short to mid term recurrence and complication rates are low, longer follow up and prospective studies are required to confirm long term oncologic safety.
