Cancers

Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes, lacking expression of estrogen receptor, progesterone receptor, and HER2. Conventional chemotherapy and immune checkpoint inhibitors provide some benefit, but resistance and relapse are frequent. The search for novel targets has therefore become central to developing more effective and durable therapies. Recent advances in proteomics, structural biology, and targeted protein degradation are rapidly expanding the repertoire of actionable molecules in TNBC. This review summarizes current and emerging therapeutic strategies for TNBC, with a focus on targeted approaches designed to address tumor heterogeneity and resistance mechanisms. To this end, recent advances in targeted therapies are examined, including immune checkpoint inhibitors, PARP inhibitors, Trop-2–directed antibody–drug conjugates, anti-angiogenic agents, PI3K/Akt/mTOR pathway inhibitors, androgen receptor antagonists, and CDK4/6 inhibitors, highlighting results from completed and ongoing clinical trials. In addition, we explore novel targets identified through integrative omics approaches, as well as the role of the tumor metabolism and microenvironment in modulating therapeutic efficacy. Finally, we outline innovative radiotherapy strategies based on targeted radiation delivery and biological integration with systemic therapies. Collectively, this review provides an updated and novel overview of the evolving TNBC therapeutic landscape and highlights promising directions for the development of next-generation, biomarker-driven treatment strategies aimed at improving patient outcomes, maintaining a broad perspective on a very large class of targets.

Background/Objectives: Fundic gland polyps (FGPs) are the most common type of gastric polyp and have increased in prevalence in the proton pump inhibitor (PPI) era. Although traditionally considered benign, dysplasia has been described in both syndromic and sporadic FGPs; data from Asian cohorts remain limited. We evaluated the prevalence of FGPs with dysplasia (FGPD) and described associated clinical and endoscopic features in a Taiwanese tertiary-care cohort. Methods: We retrospectively searched institutional pathology archives for all gastric biopsy or polypectomy specimens diagnosed as FGP between January 2000 and December 2024 and mapped these specimens to unique patients using medical record numbers. Candidate dysplastic cases underwent slide review by gastrointestinal pathologists to confirm FGPD and grade dysplasia as low- or high-grade according to standard gastric dysplasia criteria. Cases were classified as syndromic if a hereditary polyposis syndrome was documented; otherwise, they were classified as sporadic. Clinical and endoscopic variables were abstracted from electronic medical records. Patient-level prevalence estimates among patients with FGP are reported with exact 95% confidence intervals (CIs). Results: Among 35,806 unique patients with histologically confirmed FGP, 25 FGPD cases were confirmed (21 sporadic, 4 syndromic). The patient-level prevalence of sporadic FGPD was 0.059% (21/35,806; 95% CI: 0.036–0.090%). Among sporadic cases, dysplasia was low-grade in 19 (90.5%) and high-grade in 2 (9.5%). Sporadic cases occurred at a median age of 48 years (interquartile range [IQR]: 37–63.5 years), and 57.1% were female. Documented PPI exposure before the index FGPD endoscopy was present in 33.3% of patients (median documented duration: 36 months [IQR: 12–125]). No case had documented current Helicobacter pylori infection at the index evaluation. Endoscopically, sporadic FGPDs were commonly multiple, sessile, located in the gastric body/fundus, and small (median size: 0.5 cm [IQR: 0.3–0.575]). Conclusions: Sporadic FGPD was exceedingly rare in this 25-year Taiwanese cohort and was predominantly low-grade. Although typically small and body/fundus-predominant, FGPs with erythema or surface irregularity—particularly with irregular microvascular patterns on narrow-band imaging—should prompt histologic assessment to exclude dysplasia.

Introduction: Patient-reported outcomes (PROs) are increasingly valued in oncology for capturing treatment tolerability and quality of life, and they are emerging as important data sources for precision-medicine and AI-driven clinical workflows. While the EQ-5D-5L questionnaire remains a widely used standardized instrument, dynamic electronic PROs (ePROs) collected via mobile applications generate richer, higher-frequency longitudinal data. Their alignment with established PRO measures, however, is not well-understood, limiting their integration into routine care and downstream analytic applications. In the prospective OGIPRO trial (KEK-ZH 2021-D0051), patients with HER2-positive breast cancer reported well-being and symptoms via the Medidux ePRO platform alongside weekly EQ-5D-5L assessments. In this retrospective analysis, we used linear mixed-effects modeling to examine associations between: (i) dynamic ePRO well-being and the EQ-5D-5L visual analogue scale (VAS); (ii) dynamic ePRO symptom grades and EQ-5D-5L domain sums; (iii) ePRO symptom grades and EQ-5D-5L disutility using the EQ-5D-5L value set for Germany. Materials and Methods: The analytic dataset comprised 13,699 dynamic ePRO data points (3376 well-being ratings and 10,323 symptom grades across 91 symptom types) from 53 patients, forming high-frequency longitudinal patient trajectories. Of these, 252 and 226 time-aligned observations, respectively, were used for direct comparison with EQ-5D-5L VAS and domain scores. Results: Dynamic ePRO well-being showed strong agreement with EQ-5D-5L VAS (β = 1.061, 95% CI: 1.015–1.107), with low between-patient variability. In contrast, the agreement between aggregated ePRO symptom grades and EQ-5D-5L domain sums was weaker (β = 0.404, 95% CI: 0.307–0.501) and more heterogeneous across patients. The same applied to the agreement between ePRO symptom grades and EQ-5D-5L disutility (β = 0.213; 95% CI: 0.151–0.275). Discussion: Dynamic ePRO well-being aligns closely with EQ-5D-5L VAS scores, supporting its use as a pragmatic substitute in clinical and research settings. Aggregated symptom grades, however, showed limited concordance with EQ-5D-5L domains, indicating the need for more granular analyses on larger datasets. Conclusions: Overall, dynamic ePRO systems provide validated, high-resolution longitudinal patient data and represent a scalable foundation for patient monitoring and data-driven decision support in oncology, including future AI-based precision-medicine applications.