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Keywords = stage IV breast cancer

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19 pages, 5280 KB  
Article
MR-Guided Focused Ultrasound-Stimulated Microbubble Radiation Enhancement Treatment for Breast Cancer: Exploratory Imaging Outcomes
by Anneswa Mukherjee, Laurentius O. Osapoetra, Lakshmanan Sannachi, David Alberico, Maria Lourdes Anzola Pena, Joyce Yip and Gregory J. Czarnota
Cancers 2026, 18(16), 2635; https://doi.org/10.3390/cancers18162635 - 15 Aug 2026
Viewed by 452
Abstract
Background: A Phase I trial to study the efficacy and safety of MR-guided FUS-MB (focused ultrasound–microbubble) treatment combined with radiotherapy (RT) using a fully electronically MRI-guided steerable focused ultrasound system was performed. The investigation here carried out an exploratory quantitative analysis of images [...] Read more.
Background: A Phase I trial to study the efficacy and safety of MR-guided FUS-MB (focused ultrasound–microbubble) treatment combined with radiotherapy (RT) using a fully electronically MRI-guided steerable focused ultrasound system was performed. The investigation here carried out an exploratory quantitative analysis of images for the first ten participants who were treated with MRgFUS-MB therapy, identifying texture-based MRI features that changed significantly after treatment and indicating probable treatment-related changes in tumour morphology. Methods and Findings: Ten patients with stage I-IV breast cancer (Age: 64 ± 10.8) underwent 2 FUS-MB therapies throughout their radiation treatments, as deemed appropriate by a multidisciplinary team. MRI scans were performed prior to treatment and at 1- and 3-month follow-up. The tumours were segmented, and 2D and 3D features, including shape, first-order and texture features, were extracted for original and wavelet-filtered T1-weighted fat-saturated MR images. The overall significance of radiomic features in association with morphological changes in the target tumour over 1-month and 3-month follow-up in comparison to the first treatment day was investigated. Results: The five most significant features (p < 0.05) were selected using a sample-related t-test, out of which most features were wavelet-filtered first-order features. First-order wavelet-filtered robust mean absolute deviation (RMAD) emerged as the most consistent significant feature for both 2D and 3D features with sampled grid spacings of 0.5 mm and 1 mm. The volume of the tumour demonstrated a decline for 80% of patients over 3 months, as measured by the 3D mesh volume of the tumour ROI. There was a significant decline in tumour size and image heterogeneity, indicating plausible changes in the tumour microenvironment possibly related to the treatment. Conclusions: Previous preclinical studies and clinical evaluations have demonstrated the efficacy of MR-guided FUS-MB therapy. MRI image-based features from the T1-weighted MR scans over various follow-up times provide potential evidence of changes in tumour tissue heterogeneity that might be treatment-related. MRgFUS MB therapy can possibly evolve as a mode of radiotherapy enhancement in the future, which warrants further controlled validation. The availability of adequate data in the future might possibly lead to the identification of image biomarkers related to treatment response, thus providing better clinical evaluations. Full article
(This article belongs to the Section Methods and Technologies Development)
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10 pages, 548 KB  
Article
Association of Pre-Diagnosis Breast Assessment Practices and Risk Factors with Breast Cancer Stage at Diagnosis: A Single-Center Cross-Sectional Study
by Halime Seda Küçükerdem, Cengiz Yılmaz and Özden Gökdemir
J. Clin. Med. 2026, 15(16), 6288; https://doi.org/10.3390/jcm15166288 - 14 Aug 2026
Viewed by 285
Abstract
Objective: To describe breast assessment before diagnosis among women with breast cancer (BC) and examine its association with stage at diagnosis. Methods: This single-center cross-sectional study included 191 women with BC attending a medical oncology clinic. Participants completed a face-to-face questionnaire on breast [...] Read more.
Objective: To describe breast assessment before diagnosis among women with breast cancer (BC) and examine its association with stage at diagnosis. Methods: This single-center cross-sectional study included 191 women with BC attending a medical oncology clinic. Participants completed a face-to-face questionnaire on breast self-examination (BSE), clinical breast examination (CBE), mammography, and patient characteristics. The stage was obtained from medical records. Mammography history was self-reported, and screening mammography could not be distinguished from diagnostic imaging. Exploratory logistic regression compared stage IV with stages I–III. Results: At diagnosis, 41 women (21.5%) had stage IV disease. Regular monthly BSE, regular CBE, and biennial mammography were reported by 8.4%, 3.7%, and 21.4%, respectively. Metastatic disease was present in 7.3% of women who reported biennial mammography and in 25.3% of other women (p = 0.013). In the exploratory multivariable model, biennial mammography was associated with lower odds of metastatic disease (adjusted OR 0.242, 95% CI 0.067–0.869), whereas later menarche was associated with higher odds (adjusted OR 1.273, 95% CI 1.017–1.592). Smoking and hormonal medication use also showed inverse associations, but these findings may reflect confounding or selection and should not be viewed as protective. Conclusions: Self-reported biennial mammography was associated with earlier stage and lower odds of metastatic disease at diagnosis. This cross-sectional study of women with BC cannot establish causality or screening-program effectiveness. Full article
(This article belongs to the Special Issue Advances and Challenges in Colorectal Cancer)
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13 pages, 788 KB  
Article
Axillary Management in Clinically Node-Positive (cN1) Estrogen Receptor-Positive Breast Cancer
by Jennifer Den, Kamil Khanipov, Vicki Suzanne Klimberg and Raj Vaghjiani
Cancers 2026, 18(16), 2574; https://doi.org/10.3390/cancers18162574 - 11 Aug 2026
Viewed by 300
Abstract
Background/Objectives: Axillary management in breast cancer continues to de-escalate, with trials showing similar outcomes between sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) in clinically node-negative patients. However, equivalence has not been demonstrated in estrogen receptor-positive (ER+), clinically node-positive (cN1) [...] Read more.
Background/Objectives: Axillary management in breast cancer continues to de-escalate, with trials showing similar outcomes between sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) in clinically node-negative patients. However, equivalence has not been demonstrated in estrogen receptor-positive (ER+), clinically node-positive (cN1) patients. We hypothesize that SLNB would not be associated with inferior outcomes compared to ALND among this population. Methods: Using the TriNetX Network, we identified women aged ≥18 years with cN1, ER+ breast cancer who underwent axillary surgery, inclusive of both upfront surgery and neoadjuvant-treated patients. Stage IV disease was excluded. The index event was the first axillary surgery (SLNB or ALND). Propensity score matching (1:1) was performed, balancing for age, receptor status, tumor characteristics, treatment, surgical procedure, and comorbidities. Outcomes included overall survival (OS) and local recurrence (LR). Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox models. Results: A total of 1162 women were identified (SLNB 641, ALND 521). After matching, 435 patients remained in each cohort. At up to 10 years, OS was similar between groups (77% vs. 76%, HR 0.9, 95% CI 0.66–1.27). Breast recurrence occurred in 5% versus 7% (HR 0.82, 95% CI 0.47–1.42). Axillary recurrence occurred in 21% versus 24% (HR 0.9, 95% CI 0.69–1.21). None of these differences reached statistical significance. Conclusions: In ER+, cN1 node-positive breast cancer, SLNB was not associated with worse survival or recurrence compared with ALND. These real-world findings are hypothesis-generating but support the continued investigation and refinement of axillary de-escalation guidelines for clinically node-positive disease. Full article
(This article belongs to the Section Cancer Pathophysiology)
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16 pages, 1711 KB  
Article
Mammography-Based Radiomics for Prediction of Nodal Status and Disease Burden in Breast Cancer: A Temporally Validated Study
by Grzegorz Chmielewski, Rafał Stando, Hubert S. Gabryś, Maksym Fritsak, Stephanie Tanadini-Lang, Matthias Guckenberger and Stanisław Góźdź
Cancers 2026, 18(16), 2566; https://doi.org/10.3390/cancers18162566 - 10 Aug 2026
Viewed by 269
Abstract
Objectives: We evaluated the performance of mammography-based radiomics in prediction of clinical nodal status, clinical tumor stage, clinical disease stage, status of the PIK3CA mutation and concordance with the radiologist-assessed BI-RADS category. Mammography is often the first imaging modality performed in the screening [...] Read more.
Objectives: We evaluated the performance of mammography-based radiomics in prediction of clinical nodal status, clinical tumor stage, clinical disease stage, status of the PIK3CA mutation and concordance with the radiologist-assessed BI-RADS category. Mammography is often the first imaging modality performed in the screening or diagnostic workup of breast cancer. Materials and Methods: In this single-center retrospective study, we included 102 histopathologically confirmed cases of breast cancer from 100 patients. The tumor region and whole-breast parenchyma were contoured on 368 craniocaudal and mediolateral-oblique mammograms. Cases were temporally split into training and test sets by histopathological diagnosis date (training: 70%, held-out test: 30%). Six linear models were tuned by 5-fold x 3-repeat stratified cross-validation. The winning model per endpoint was applied once to the test set. We report AUCs with 95% confidence intervals, permutation p-values and Benjamini–Hochberg false discovery rate (BH-FDR) correction across five endpoints. Results: Three of the studied endpoints reached significance after BH-FDR correction: clinical nodal status (cN0 vs. cN-positive; AUC: 0.726 (95% CI: 0.501–0.886)), clinical tumor stage (cT1-2 vs. cT3-4; AUC: 0.792 (95% CI: 0.575–0.929)) and overall disease stage (I–II vs. III–IV; AUC: 0.778 (95% CI: 0.572–0.917)). Mammography-based radiomics failed to predict the presence of PIK3CA mutation and concordance with radiologist-assessed BI-RADS category. Conclusions: Mammography-based radiomics has shown a hypothesis-generating discriminative value for differentiation between cN-negative and cN-positive disease, early from advanced clinical tumor stage, and early from advanced overall disease stage in breast cancer. Mammography-based radiomics did not predict PIK3CA status and did not discriminate between radiologist-assessed BI-RADS 4 and 5 groups. Full article
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11 pages, 1479 KB  
Case Report
Germline PALB2 Genetic Variant Associated with Rapid Metastatic Progression and Poor Survival in Two Kazakh Women with Breast Cancer: A Case Study
by Gulnur Zhunussova, Nazgul Omarbayeva, Aigul Zhunussova, Diana Abdullayeva, Liliya Skvortsova, Nursultan Nurdinov and Ainash Oshibayeva
Genes 2026, 17(8), 913; https://doi.org/10.3390/genes17080913 - 31 Jul 2026
Viewed by 467
Abstract
Background: Germline PALB2 variants are associated with hereditary breast cancer risk, but their clinical impact in Central Asian populations remains largely uncharacterized. This case study aims to evaluate the clinical significance of PALB2 variants in two Kazakh women with early-onset breast cancer. [...] Read more.
Background: Germline PALB2 variants are associated with hereditary breast cancer risk, but their clinical impact in Central Asian populations remains largely uncharacterized. This case study aims to evaluate the clinical significance of PALB2 variants in two Kazakh women with early-onset breast cancer. Methods: Molecular genetic testing identified germline PALB2 pathogenic variants (NM_024675.4:c.18_22delGAAGC and NM_024675.4:c.1034T>G) in two Kazakh women with early-onset invasive ductal carcinoma. Clinical courses, treatment responses, and outcomes were followed. Results: Neither patient had a reported family history of breast or other malignancies. Patient 1, a 26-year-old pregnant woman, was diagnosed with stage IIIB luminal B, HER2-negative invasive ductal carcinoma and received neoadjuvant chemotherapy, radical surgery, radiotherapy, endocrine therapy, and subsequent treatment for metastatic disease. Despite an initial response, she developed extensive skeletal metastases and died from metastatic breast cancer. Patient 2, a 33-year-old woman, presented with de novo stage IV luminal B, HER2-negative invasive ductal carcinoma with hepatic metastases. Following multimodal treatment, including chemotherapy, surgery, radiotherapy, endocrine suppression, and systemic therapy for disease progression, she experienced further metastatic spread and ultimately died from breast cancer-related complications. Conclusions: Both patients exhibited aggressive clinical courses characterized by early disease onset, metastatic progression, and poor outcomes despite comprehensive treatment. These cases highlight the potential clinical significance of germline PALB2 variants in apparently sporadic breast cancer and underscore the importance of genetic testing, risk assessment, and genetic counselling in young breast cancer patients, particularly in underrepresented. Full article
(This article belongs to the Special Issue Genome Sequencing and Genetic Testing for Cancer)
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63 pages, 3034 KB  
Review
Association Between the Dietary Inflammatory Index (DII) and Head and Neck Cancer Incidence—A Narrative Review
by Starska-Kowarska Katarzyna
Nutrients 2026, 18(15), 2421; https://doi.org/10.3390/nu18152421 - 24 Jul 2026
Viewed by 601
Abstract
Head and neck cancer (HNC) comprises a heterogeneous group of tumours, most often of squamous cell origin, characterized by both high morbidity and mortality rates. It is the seventh most common form of cancer diagnosed in humans, accounting for approximately 4.7% of all [...] Read more.
Head and neck cancer (HNC) comprises a heterogeneous group of tumours, most often of squamous cell origin, characterized by both high morbidity and mortality rates. It is the seventh most common form of cancer diagnosed in humans, accounting for approximately 4.7% of all cancers. Among HNCs, neck squamous cell carcinoma (HNSCC) is predicted to become the most common form of human cancer. Some sources include oesophagus (ESCC) in this group due to their similar histology, being described as upper aerodigestive tract cancers (UADT). Unfortunately, 60–70% of cases are diagnosed late, i.e., at clinical stages III-IV. As a result, despite modern surgical techniques and oncological treatments, the survival rate remains below 40–60% due to frequent lymph node metastases and local tumour recurrence. There is a growing concern that diet and inflammatory dietary components may influence the initiation and development of HNSCC. The inflammatory potential of diets can be quantified by the Dietary Inflammatory Index (DII). The DII was derived from an analysis of 45 dietary constituents that either increase or decrease inflammation. Several recent clinical studies have noted a significant relationship between DII score and many inflammation-associated chronic diseases, such as obesity, cardiovascular and neurodegenerative disorders, and diabetes, and the incidence of various human cancers, i.e., prostate, ovarian, breast, colorectal cancer, and HNC. However, few studies have investigated the relationship between DII and HNSCC, with most being limited to observational, case-control, and cross-sectional studies. Therefore, the aim of this narrative review is to present the substantial oncological aspects of DII, discuss the use of DII and its modification, the Energy-Adjusted Dietary Inflammatory Index (E-DII), as indicators of HNSCC risk. It also introduces key diet-induced pro- and anti-inflammatory mechanisms and the cellular molecular signalling pathways determining the carcinogenesis of HNSCC. It provides a comprehensive overview of the current literature, including key opinion-forming systematic reviews, as well as molecular, observational, cross-sectional and case-control studies, all of which are accessible via scholarly databases such as PubMed/EMBASE/Web of Science. Thus, the work serves as a compendium of up-to-date knowledge on the relationship between DII/ED-II score and HNSCC etiopathogenesis and the influence of a diet-induced persistent inflammatory microenvironment. Full article
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19 pages, 852 KB  
Article
Determinants of Early-Stage Breast Cancer Presentation in Western Kazakhstan: A Population-Based Analysis of Urban–Rural Disparities and Diagnostic Pathways (2015–2025)
by Dinara Zholmukhamedova, Maiya Taushanova, Dariusz Walkowiak, Lyudmila Yermukhanova, Laura Danyarova, Indira Karibayeva, Aizat Aimakhanova, Aizat Seidakhmetova and Anara Tulyayeva
Medicina 2026, 62(8), 1431; https://doi.org/10.3390/medicina62081431 - 23 Jul 2026
Viewed by 460
Abstract
Background and Objectives: Breast cancer is the leading oncological diagnosis among women in Kazakhstan, yet a substantial proportion of cases are still detected beyond the earliest stages, particularly in peripheral regions such as Aktobe. Despite a national mammography screening programme covering women aged [...] Read more.
Background and Objectives: Breast cancer is the leading oncological diagnosis among women in Kazakhstan, yet a substantial proportion of cases are still detected beyond the earliest stages, particularly in peripheral regions such as Aktobe. Despite a national mammography screening programme covering women aged 40–70 years since 2018, structural differences in access to early diagnosis—related to geography, socioeconomic circumstances, and the diagnostic pathway—may compromise outcomes. We aimed to identify factors independently associated with early-stage presentation and to characterise the temporal pattern of early-stage presentation without assuming a monotonic trend. Methods and Materials: We conducted a retrospective, population-based analytical study of all confirmed breast cancer cases (ICD-10 C50) registered in the Aktobe regional cancer registry and diagnosed between 1 January 2015 and 31 December 2025 (n = 2232). The outcome was early-stage presentation, defined literally as Stages I–IIa at diagnosis, with Stages IIb–IV as the comparator; this is a stage-at-presentation classification and is not intended to indicate surgical operability or treatment sequence. Multivariable logistic regression estimated adjusted odds ratios (aORs). Two models were used: Model A included age, sex, residence, administrative nationality, employment/social status, and calendar year; Model B additionally included the diagnostic pathway, which may lie on the causal pathway between structural determinants and stage. Calendar year was modelled as a categorical variable, and a complementary phase-based model (2015–2017, 2018–2019, 2020–2022, 2023–2025) was fitted. A residence-by-year interaction; a multinomial sensitivity analysis separating Stages IIb, III, and IV; discrimination (AUC, Brier score); and calibration (Hosmer–Lemeshow test, calibration plot) were also assessed. Results: Of 2232 patients (99.1% female; mean age 57.0 ± 12.5 years), 1323 (59.3%) presented at Stages I–IIa. In Model A, rural residence (aOR 0.77, 95% CI 0.64–0.93; p = 0.006), unemployment relative to employment (aOR 0.69, 95% CI 0.52–0.90; p = 0.007), Russian administrative nationality (aOR 0.64, 95% CI 0.50–0.82; p < 0.001), and other non-Kazakh nationalities (aOR 0.73, 95% CI 0.58–0.94; p = 0.012) were independently associated with lower odds of Stage I–IIa presentation. In Model B, patient-initiated (self-referral) presentation was associated with lower odds relative to clinical examination room detection (aOR 0.46, 95% CI 0.30–0.72; p < 0.001), whereas organised screening was not significantly associated (aOR 1.52, 95% CI 0.95–2.43; p = 0.082). The calendar-year pattern was clearly non-linear (categorical vs. linear year: likelihood-ratio χ2 = 76.1, df = 9, p < 0.001): odds of Stage I–IIa presentation peaked in 2018 (aOR 2.49, 95% CI 1.57–3.93 vs. 2015), were lowest in 2022 (aOR 0.64, 95% CI 0.42–0.97), and partially recovered thereafter. In the phase-based model (reference 2015–2017), the aORs were 1.62 (95% CI 1.22–2.15) for 2018–2019, 0.54 (95% CI 0.41–0.69) for 2020–2022, and 0.62 (95% CI 0.46–0.84) for 2023–2025. Model discrimination was limited (AUC 0.648, 95% CI 0.625–0.671; Brier score 0.226) with acceptable calibration (Hosmer–Lemeshow χ2 = 8.38, df = 8, p = 0.40). Conclusions: In this registry-based cohort, rural residence, unemployment, non-Kazakh administrative nationality, and patient-initiated presentation were independently associated with lower odds of early-stage breast cancer presentation. The temporal pattern was non-monotonic, with the highest odds around the 2018 screening expansion, a marked reduction during 2020–2022, and only partial recovery thereafter. These are observational associations rather than causal or programme-evaluation findings; they should be interpreted as hypothesis-generating and require confirmation with screening-process, service-capacity, and patient-level access data. Full article
(This article belongs to the Section Epidemiology & Public Health)
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11 pages, 1251 KB  
Article
Programmed Death-Ligand 1 Expression in Triple-Negative Breast Cancer: Insights from a Mexican Cohort
by Cynthia Villarreal-Garza, César Octavio Lara-Torres, Jesus Edgardo Hernandez-Hernandez, Daniela Vázquez Juárez, Gabriela Sofía Gómez-Macías, Paula Cabrera-Galeana, Fany Iris Porras-Reyes, Víctor Manuel Pérez-Sánchez, Antonio Nateras-Pérez, Gabriela Lugo-Martinez, Alejandro Aranda-Gutierrez and Alejandro Mohar
Cancers 2026, 18(14), 2182; https://doi.org/10.3390/cancers18142182 - 8 Jul 2026
Cited by 1 | Viewed by 545
Abstract
Background: Pembrolizumab-containing regimens have become the standard of care across the spectrum of triple-negative breast cancer (TNBC). While their use in the neoadjuvant setting is independent of biomarker status, their application in metastatic disease remains strictly contingent upon PD-L1 expression. Given that [...] Read more.
Background: Pembrolizumab-containing regimens have become the standard of care across the spectrum of triple-negative breast cancer (TNBC). While their use in the neoadjuvant setting is independent of biomarker status, their application in metastatic disease remains strictly contingent upon PD-L1 expression. Given that PD-L1 prevalence can vary significantly by ethnicity and geography, the lack of specific data for the Mexican population creates a challenge for optimizing treatment in the metastatic setting. This study sought to characterize PD-L1 positivity rates in a Mexican TNBC cohort to better define the local molecular landscape. Methods: We conducted a retrospective study across two cancer centers in Mexico to assess PD-L1 positivity in a cohort of women with TNBC (stages I–IV) diagnosed between 2006 and 2021. PD-L1 expression was assessed and evaluated centrally using the 22C3 pharmDx assay, with a Combined Positive Score (CPS) of ≥1 considered positive. We explored the association between PD-L1 expression and clinicopathological features. Results: Of the 298 TNBC patients identified, 285 (96%) had sufficient tissue for CPS evaluation and thus were included in the analysis. PD-L1 positivity was observed in 29.1% of the cohort, and 13.3% of patients had a CPS ≥ 10. PD-L1 positivity was associated with higher histological grades (91.3% vs. 78.5%, p = 0.035) and TILs ≥ 30% (22.2% vs. 10.0%, p = 0.007). Additionally, pre-treatment surgical specimens were more frequently PD-L1 positive than tumor biopsies (56.6% vs. 30.7%, p < 0.001). Conclusions: This study characterizes the PD-L1 landscape in Mexican women with TNBC, reporting a 29.1% prevalence of CPS ≥ 1. The strong association between PD-L1 positivity and high TILs/histological grade highlights the role of the immune microenvironment in these aggressive phenotypes. Given the significant variability observed between specimens (biopsy vs. surgical), clinicians should consider the dynamic nature of PD-L1 expression when choosing treatment strategies. Full article
(This article belongs to the Section Molecular Cancer Biology)
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9 pages, 10403 KB  
Case Report
Complete Imaging Resolution of Ductal Carcinoma In Situ During Osimertinib Therapy for Synchronous EGFR Exon 19-Mutant Non-Small Cell Lung Cancer: A Case Report
by Leticia Assad Maia Sandoval, Richard E. Sharpe, Austin J. Fullenkamp, Erinn Downs and Lida Mina
Int. J. Mol. Sci. 2026, 27(13), 5995; https://doi.org/10.3390/ijms27135995 - 3 Jul 2026
Cited by 1 | Viewed by 371
Abstract
A 64-year-old Asian woman diagnosed with synchronous breast ductal carcinoma in situ (DCIS) and stage IV EGFR-mutated non-small cell carcinoma of the lung (NSCLC). A decision was made to defer management of the DCIS and initiate Osimertinib for lung cancer treatment, since this [...] Read more.
A 64-year-old Asian woman diagnosed with synchronous breast ductal carcinoma in situ (DCIS) and stage IV EGFR-mutated non-small cell carcinoma of the lung (NSCLC). A decision was made to defer management of the DCIS and initiate Osimertinib for lung cancer treatment, since this was a life-limiting diagnosis. At 9 months, restaging FDG-PET CT showed an interval response in the NSCLC and complete loss of FDG avidity at the biopsy-proven DCIS site. Breast MRI confirmed complete imaging resolution of the DCIS. The clinical resolution of breast DCIS during third-generation EGFR inhibitor therapy has not been previously reported in humans and highlights a potential role for the EGFR/HER2 (ERBB) pathway in pre-invasive breast cancer. Full article
(This article belongs to the Special Issue Breast Cancer: From Pathophysiology to Novel Therapies, 2nd Edition)
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18 pages, 798 KB  
Article
Integrated Chinese and Western Medicine for Breast Cancer Patients with Depression—Association with Survival and Healthcare Utilization: A Nationwide Retrospective Cohort Study in Taiwan
by Chingying Liang, Yen-Chun Huang, Jiun-Liang Chen, Chi Wen Chen and Mingchih Chen
Healthcare 2026, 14(10), 1406; https://doi.org/10.3390/healthcare14101406 - 20 May 2026
Viewed by 737
Abstract
Background: Breast cancer (BC) survivors frequently experience depression, which is associated with poorer quality of life (QoL), increased healthcare utilization, and worse prognosis. Although traditional Chinese medicine (TCM) is commonly used as an adjunctive therapy among Chinese populations for cancer-related symptom relief [...] Read more.
Background: Breast cancer (BC) survivors frequently experience depression, which is associated with poorer quality of life (QoL), increased healthcare utilization, and worse prognosis. Although traditional Chinese medicine (TCM) is commonly used as an adjunctive therapy among Chinese populations for cancer-related symptom relief and supportive care, population-based evidence remains limited regarding whether integrated Chinese and Western medicine (ICWM) confers measurable benefits over Western medicine (WM) alone in terms of healthcare utilization and survival. Taiwan’s National Health Insurance (NHI) system offers a unique nationwide setting to address this gap because it reimburses patients for both WM and TCM services and captures care from a large number of TCM clinics across Taiwan, allowing evaluation of adjunctive TCM use in routine clinical practice at a scale rarely possible in prior studies. We used emergency department visits, hospitalization, and length of stay as pragmatic proxy indicators of patients’ daily functioning and disease burden. Leveraging a 10-year enrollment window (2004–2013) and up to 17 years of follow-up, we hypothesized that ICWM would be associated with a reduced risk of acute care events and lower healthcare expenditures compared with WM alone. This hypothesis was examined in a large cohort of breast cancer patients treated across nearly 4000 medical facilities nationwide, encompassing the entire Taiwanese population. Methods: A retrospective cohort study was performed to analyze Taiwan’s National Health Insurance Research Database and Cancer Registry. Women newly diagnosed with breast cancer between 2004 and 2013 who subsequently developed depression (≥3 outpatient diagnoses or 1 hospitalization) were followed until death or 31 December 2021. Patients receiving ≥30 cumulative days of TCM after diagnosis were classified as the ICWM group, whereas those receiving <30 days were classified as the WM group. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for all-cause mortality. Healthcare utilization, including emergency department visits, hospitalization, and medical expenditures, was analyzed on a per-person-year basis. Results: A total of 1193 patients were included, with 488 in the WM group and 705 in the ICWM group. Compared with WM users, ICWM users were younger, had lower body mass index, and were more likely to have stage 0–II disease. ICWM was associated with lower total, inpatient, and emergency healthcare expenditures per person-year, as well as fewer emergency visits per person-year, although outpatient and overall visits were higher. In stage-stratified multivariable analyses, ICWM was associated with lower all-cause mortality in both stage 0–II disease (aHR = 0.61, 95% CI: 0.39–0.94) and stage III–IV disease (aHR = 0.38, 95% CI: 0.21–0.67). Kaplan–Meier analyses likewise showed significantly better overall survival in the ICWM group in both early-stage and advanced-stage disease. Conclusions: In this nationwide retrospective cohort of breast cancer patients with depression, adjunctive ICWM was associated with better survival, lower acute care utilization, and lower healthcare expenditures compared with WM alone. However, because quality of life was not directly measured and the study was based on observational data, QoL-related interpretations should be made cautiously, with healthcare utilization outcomes viewed as indirect proxy indicators rather than direct evidence of improved daily QoL. Full article
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13 pages, 1763 KB  
Article
Exploration of Optimal Synergistic Treatment Strategies of Postoperative Radiotherapy and Immunotherapy in Early-Stage Breast Cancer
by Qingyao Shang, Hanyu Wang, Yan Zhuang, Jennifer K. Plichta, Samantha M. Thomas, Meishuo Ouyang, Sheng Luo and Xin Wang
Cancers 2026, 18(7), 1145; https://doi.org/10.3390/cancers18071145 - 2 Apr 2026
Viewed by 886
Abstract
Background: The optimal sequencing of radiotherapy and immunotherapy in early-stage breast cancer remains uncertain. Although synergistic interactions between radiotherapy and immunotherapy have been widely reported, most available evidence derives from advanced disease with high tumor burden. Whether treatment sequencing influences outcomes in [...] Read more.
Background: The optimal sequencing of radiotherapy and immunotherapy in early-stage breast cancer remains uncertain. Although synergistic interactions between radiotherapy and immunotherapy have been widely reported, most available evidence derives from advanced disease with high tumor burden. Whether treatment sequencing influences outcomes in postoperative adjuvant therapy has not been well defined. Methods: Patients with stage I–III human epidermal growth factor receptor 2 (HER2)-negative breast cancer who underwent surgery followed by both adjuvant radiotherapy and immunotherapy were identified from the National Cancer Database. According to treatment initiation dates, patients were classified into immunotherapy-first and radiotherapy-first groups. Overall survival was compared using Kaplan–Meier analysis and weighted Cox regression. Baseline imbalances were adjusted using inverse probability of treatment weighting. Prespecified subgroup analyses were conducted based on adjuvant chemotherapy status and radiotherapy fractionation regimen. A sensitivity analysis was performed in an independent cohort of stage IV inoperable patients. Results: A total of 3813 patients were included. Immunotherapy-first sequencing was associated with improved overall survival compared with radiotherapy-first sequencing after weighted (HR 0.71; 95% CI 0.56–0.89). The survival benefit was most evident among patients receiving adjuvant chemotherapy (HR 0.63; 95% CI 0.48–0.84), whereas no significant difference was observed in patients without chemotherapy (HR 1.01; 95% CI 0.71–1.44). Subgroup analysis according to radiotherapy fractionation demonstrated a significant advantage of immunotherapy-first sequencing in patients treated with conventional fractionation radiotherapy (HR 0.58; 95% CI 0.36–0.92), but not in those receiving hypofractionated radiotherapy (HR 0.44; 95% CI 0.17–1.13). In stage IV inoperable patients, no survival difference was detected between sequencing strategies (HR 1.04; 95% CI 0.88–1.23). Conclusions: For postoperative patients with low residual tumor burden, particularly those receiving adjuvant chemotherapy, immunotherapy-first strategy may provide stronger synergistic effects and lead to improved survival. In addition, conventional fractionation radiotherapy with lower doses per fraction appears to facilitate more effective interaction with immunotherapy compared with hypofractionated regimens. Prospective trials are needed for further validation. Full article
(This article belongs to the Special Issue Combination Therapy for the Treatment of Breast Cancer)
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15 pages, 1317 KB  
Article
Entosis in Colorectal, Lung, and Breast Cancer: Associations with Clinicopathological Features, Patient Outcomes, and Copy Number Alteration Landscape
by Ksenia A. Gaptulbarova, Sergey V. Vtorushin, Marina K. Ibragimova, Irina A. Tsydenova, Natalia A. Tarabanovskaya, Vitaly P. Shubin, Aleksey S. Tsukanov, Evgeny O. Rodionov, Sergey I. Achkasov and Nikolai V. Litviakov
J. Mol. Pathol. 2026, 7(1), 12; https://doi.org/10.3390/jmp7010012 - 17 Mar 2026
Viewed by 1702
Abstract
Objective: This study examined the frequency of entosis in solid tumors of various origins (colorectal cancer, breast cancer, and lung cancer) and its association with clinical and pathological characteristics. It also examined survival and copy number alterations (CNAs) in genes associated with [...] Read more.
Objective: This study examined the frequency of entosis in solid tumors of various origins (colorectal cancer, breast cancer, and lung cancer) and its association with clinical and pathological characteristics. It also examined survival and copy number alterations (CNAs) in genes associated with stem cells. The aim was to assess the potential prognostic value of entotic events in tumors. Methods: A total of 238 patients were included: 96 with colorectal cancer (CRC), 45 with lung cancer (LC), and 97 with breast cancer (BC). Entotic cell-in-cell (CIC) structures were evaluated on hematoxylin–eosin–stained slides using Mackay’s criteria. A CIC frequency >0.1 per 20 high-power fields was considered positive. Clinicopathological parameters, overall survival (CRC), metastasis-free survival (LC and BC), and CNA profiles of stemness-related genes were analyzed. Amplifications of MAP1LC3A and other chromosomal loci were assessed. Results: CRC demonstrated the highest entosis rate, more than two-fold higher compared with BC and LC (p < 0.05). Entosis correlated with high tumor grade (G3) in CRC (p = 0.03). In LC, CIC-positive tumors were more frequent in patients with lymph-node metastases (p = 0.02), whereas in BC, the opposite trend was observed (p = 0.02). It was noted that in patients with stage III–IV LC, the frequency of entosis was significantly higher than in patients with stage I–II cancer (p = 0.03). CIC-positive status was associated with poorer overall survival in CRC (p = 0.03) and reduced metastasis-free survival in LC (p = 0.011). In breast cancer, no statistically significant survival differences were observed. Tumors harboring two or more stemness-gene amplifications showed significantly higher entosis frequency regardless of tumor site. A strong association was identified between entosis and MAP1LC3A amplification. Conclusions: Enosis is not a random morphological phenomenon but a process associated with unfavorable tumor characteristics, high malignancy, reduced survival, and amplification of stem cell-related genes. The results of this study confirm the working hypothesis that entosis may contribute to the emergence of aneuploid clones of tumor cells, including those containing amplifications of stem cell-associated genes. This positions entosis as a potential factor in tumor genetic heterogeneity, which is particularly important in the context of therapeutic selection pressure. The observed association between high entosis frequency and the presence of ≥2 stem cell gene amplifications, as well as its association with poor prognosis in colorectal and lung cancer, highlights its potential value as a prognostic indicator. Furthermore, MAP1LC3A amplification data may serve as a molecular marker of entotic activity and a potential therapeutic target. Full article
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11 pages, 722 KB  
Article
Clinical Significance of Achieving No Evidence of Disease in HER2-Positive Metastatic Breast Cancer: A Multicenter Study by Turkish Oncology Group (TOG)
by Bengü Dursun, Şendağ Yaslıkaya, Serhat Sekmek, Tuğba Önder, Hasan Çağrı Yıldırım, Ömer Acar, Nadiye Sever, Savaş Gökçek, Sercan Ön, Ferit Aslan, Gül Sema Keskin, Zehra Sucuoğlu İşleyen, Gözde Savaş, Mehmet Emin Kalender, Semra Paydaş, Öznur Bal, Ülkü Yalçıntaş Arslan, Mustafa Şahbazlar, Burcu Çakar, Hacı Mehmet Türk and Hakan Akbulutadd Show full author list remove Hide full author list
Cancers 2026, 18(6), 915; https://doi.org/10.3390/cancers18060915 - 12 Mar 2026
Cited by 1 | Viewed by 809
Abstract
Background: Achieving no evidence of disease (NED) in HER2-positive metastatic breast cancer (MBC) has been proposed as a response-state marker for durable disease control. However, its clinical significance and predictive factors are not yet well established. Methods: In this multicenter retrospective [...] Read more.
Background: Achieving no evidence of disease (NED) in HER2-positive metastatic breast cancer (MBC) has been proposed as a response-state marker for durable disease control. However, its clinical significance and predictive factors are not yet well established. Methods: In this multicenter retrospective study at 13 oncology centers in Turkey, we analyzed 118 patients with stage IV HER2-positive MBC who received trastuzumab-based first-line therapy and remained progression-free for at least 36 months. Patients were stratified by radiologically defined NED status according to RECIST v1.1. Clinicopathological features were compared between groups, and predictors of NED were identified using logistic regression. Progression-free survival (PFS) was estimated by Kaplan–Meier analysis and assessed with Cox regression. Results: Of the 118 patients, 55 (46.6%) achieved NED. Compared with patients who did not achieve NED, those attaining NED were younger (median 46 vs. 53 years, p = 0.013), had better ECOG performance status (p = 0.005), were more likely to have HER2 IHC 3+ status (p = 0.015), and higher histologic grade tumors (p = 0.013). In multivariable logistic regression, ECOG PS 0 (vs. 1 ; OR = 5.99, p = 0.005), HER2 IHC 3+ (vs. IHC 2+/ISH+; OR = 4.79, p = 0.035), and histologic grade ≤2 (vs. grade 3 ; OR = 0.25, p = 0.011) were independently associated with NED attainment. Patients who achieved NED had experienced significantly longer PFS than those who did not (median 131 months vs. 66 months; p < 0.005). In multivariate Cox regression, NED remained independently associated with prolonged PFS (HR = 0.24, p = 0.003). Metastasis-directed local therapy and treatment regimen (trastuzumab vs. trastuzumab + pertuzumab) were not independently associated with NED attainment or PFS. Conclusions: In this multicenter cohort of pre-selected long-term responders, nearly half of HER2-positive MBC patients achieved radiologic NED. Radiologic NED was independently associated with prolonged PFS within this enriched population. Factors associated with NED attainment included favorable ECOG performance status, HER2 IHC 3+ expression, and high tumor grade; given the wide confidence intervals, these estimates should be interpreted cautiously as exploratory and hypothesis-generating. Full article
(This article belongs to the Section Cancer Metastasis)
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16 pages, 607 KB  
Article
Comparable Access, Different Outcomes: Breast Cancer Survival Among Syrian Refugees and Turkish Patients in Türkiye
by Ilker Nihat Ökten, Tuba Baydaş, Canan Karan, Oğuzhan Kesen, İbrahim Çil and Fatih Teker
Curr. Oncol. 2026, 33(3), 155; https://doi.org/10.3390/curroncol33030155 - 8 Mar 2026
Cited by 1 | Viewed by 1056
Abstract
Background: Breast cancer outcomes are influenced by tumor biology, stage at diagnosis, and access to timely care. Refugee populations may experience disparities in cancer outcomes despite formal access to healthcare services. Türkiye hosts the largest population of Syrian refugees globally and provides universal [...] Read more.
Background: Breast cancer outcomes are influenced by tumor biology, stage at diagnosis, and access to timely care. Refugee populations may experience disparities in cancer outcomes despite formal access to healthcare services. Türkiye hosts the largest population of Syrian refugees globally and provides universal access to oncology care, offering a unique context to examine equity in breast cancer outcomes. Methods: We performed a retrospective cohort study of female patients diagnosed with invasive breast cancer between 2013 and 2022 at two tertiary oncology centers in Gaziantep, Türkiye. Patients were grouped as Syrian refugees or Turkish citizens based on recorded nationality. Baseline clinicopathologic features and stage at diagnosis were compared between groups. Overall survival (OS) was estimated by the Kaplan–Meier method and compared using log-rank tests. Survival analyses were performed overall and stratified by stage category (I–III vs. IV). Cox proportional hazards regression was used to evaluate the association between ethnicity and OS with adjustment for stage and molecular subtype (and other prespecified covariates as appropriate). Treatment delivery patterns (systemic therapy and radiotherapy) were descriptively compared to evaluate access after entry into care. Results: Among 499 patients (150 Syrian refugees; 349 Turkish citizens), Syrian patients were younger at diagnosis and more frequently presented with de novo metastatic disease. In the overall cohort with survival data (n = 430), unadjusted OS differed by ethnicity; however, survival differences were attenuated after stratification by stage. In stage I–III disease, OS did not significantly differ between groups, and in stage IV disease, median OS was comparable between ethnicities. In multivariable analysis adjusting for stage and molecular subtype, ethnicity was not independently associated with OS, whereas stage and molecular subtype remained prognostic. Treatment delivery patterns in both the non-metastatic and metastatic settings were broadly similar between groups. Conclusions: Within a universal healthcare system, the dominant disparity between Syrian refugees and Turkish citizens was more advanced stage at presentation. After accounting for stage and tumor biology, ethnicity itself was not independently associated with overall survival, suggesting that efforts to reduce outcome gaps should prioritize earlier diagnosis and linkage to care. Full article
(This article belongs to the Section Breast Cancer)
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19 pages, 586 KB  
Article
Perceived Stress and Sociodemographic Factors Among Saudi Women with Breast Cancer: A Cross-Sectional Study
by Sahar Abdulkarim Al-Ghareeb, Ahmad Aboshaiqah, Mousa Yahia Asiri, Homoud Ibrahim Alanazi and Ahmad M. Rayani
J. Clin. Med. 2026, 15(3), 1168; https://doi.org/10.3390/jcm15031168 - 2 Feb 2026
Cited by 1 | Viewed by 840
Abstract
Background: and objective: Globally, breast cancer (BC) raises global health concerns, being the most common cancer. Women with BC experience a significant increase in perception of stress. Therefore, this study aims to evaluate the stress levels and associated sociodemographic and clinical factors among [...] Read more.
Background: and objective: Globally, breast cancer (BC) raises global health concerns, being the most common cancer. Women with BC experience a significant increase in perception of stress. Therefore, this study aims to evaluate the stress levels and associated sociodemographic and clinical factors among BC women in Saudi Arabia. Methods: A cross-sectional study was conducted between January and May 2025. Women diagnosed with BC, who were at least 18 years old, were recruited conveniently from outpatient and inpatient departments in King Fahad Specialist Hospital, Dammam, Saudi Arabia. Data were collected in the Arabic language through self-reported questionnaires, including sociodemographic/clinical characteristics and the Cohen’s Perceived Stress Scale. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 27. Results: A total of 200 participants were included in the study. The mean stress perception score was 26.52 ± 7.34. A high proportion (71.5%) of the sample reported elevated stress. A significant association was observed between age and stress levels. Most women aged 20–40 and 41–60 reported high stress, compared to women in the 61–80 age group (p = 0.003). Among all predictors, age was the only variable significantly associated with stress scores. Increasing age was associated with lower stress levels (B = −0.179, p = 0.013), indicating that younger participants tended to report higher stress. This corresponds to an adjusted decrease of approximately 1.8 points in the PSS-10 score per 10-year increase in age. Although participants with Stage IV cancer showed higher stress scores compared to those with Stage I cancer, this association approached but did not reach statistical significance (p = 0.054). Conclusions: This study highlights the substantial psychological burden experienced by women living with BC in Saudi Arabia. The majority of participants reported high levels of perceived stress. Younger women were particularly vulnerable to elevated stress. These findings highlight the need for targeted psychosocial support within oncology care to improve emotional well-being and quality of life. Full article
(This article belongs to the Section Oncology)
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