Background/Objectives: Neoadjuvant dual HER2 blockade is standard for HER2-positive breast cancer, yet response rates vary based on tumor biology. This multicenter study aimed to identify clinicopathological predictors of pathological complete response (pCR), focusing on quantitative hormone receptor (HR) expression and HER2 staining intensity, and to evaluate their impact on survival. Methods: This multicenter retrospective study included 290 female patients diagnosed with HER2-positive early or locally advanced breast cancer treated with neoadjuvant trastuzumab and pertuzumab-based regimens (anthracycline-based [AC-THP] or non-anthracycline [TCHP]) across six centers. HR expression was stratified into low (<50%) and high (≥50%) categories. Multivariable regression analyses identified predictors of pCR, Disease-Free Survival (DFS), and Overall Survival (OS). Results: The pCR rate was 51.4%. Multivariate analysis identified HR negativity (OR = 2.80; p < 0.001) and strong HER2 overexpression (IHC Score 3) (OR = 2.20; p = 0.037) as primary predictors. Uniquely, patients with low HR expression (<50%) achieved significantly higher pCR rates (65.9%) than strongly positive cases (36.6%; p = 0.001), biologically mimicking hormone-negative disease. The non-anthracycline TCHP regimen showed a strong trend toward superior efficacy (OR = 2.22; p = 0.054). pCR was the sole independent predictor of OS (HR = 0.134; p = 0.009). Crucially, adjusting for pCR unmasked hormone-negative status as a significant risk factor for recurrence (HR = 2.49; p = 0.028), highlighting its dual nature: high chemosensitivity but inherent biological aggression. Conclusions: “Strong” HER2 positivity and “weak” HR expression (<50%) are the primary determinants of pCR. pCR remains the strongest surrogate for survival, neutralizing initial risk factors. These findings support using quantitative biomarker thresholds for personalization and reinforce the efficacy of non-anthracycline regimens.

Background/Aims: Functional dyspepsia (FD) is diagnosed in the absence of an identifiable organic cause. Pancreatic enzyme insuf ficiency (PEI) remains an underrecognized condition in these patients. This study aimed to investigate the prevalence of PEI among FD patients unresponsive to standard therapy and to evaluate its clinical and biochemical characteristics. Materials and Methods: A total of 154 patients diagnosed with FD were followed, among which 66 patients who did not respond to at least 4 weeks of standard treatment, including acid-reducing therapies, prokinetics, and antidepressants, were evaluated. Additionally, 34 healthy volunteers were included as a control group. Organic pathologies were excluded in all 66 patients with FD resistant to stan dard treatment using endoscopy, endoscopic biopsy, and imaging methods. Fecal elastase-1 (FE-1) enzyme levels were measured to determine the prevalence of PEI in both groups. Results: Pancreatic enzyme insufficiency was detected in 5 (7.57%) of the 66 treatment-resistant FD patients, while none of the con trols had PEI. The prevalence of PEI was significantly higher in diabetic patients than in non-diabetic patients within the study group (P = .037). Patients with diarrhea, sticky stools, and frequent foul-smelling stools exhibited a higher prevalence of PEI (P = .022, P = .001, and P = .004, respectively). In the study group, PEI patients had lower serum calcium, phosphorus, and magnesium levels than the control group (P = .018, P = .011, and P = .001, respectively). Conclusion: Pancreatic enzyme insufficiency was identified in 7.57% of patients resistant to standard treatment. In patients resistant to standard therapy for at least 4 weeks, the presence of symptoms such as diarrhea, sticky stools, and foul-smelling stools, along with diabetes mellitus and low serum calcium, phosphorus, and magnesium levels, may warrant consideration of PEI as a potential underlying condition. Cite this article as: Kemik F, Ceylan G, Aydin AF, et al. The role of pancreatic enzyme insufficiency in the etiology of functional dyspepsia resistant to standard treatment. Turk J Gastroenterol. 2025;36(7):467-473.

Background: Trastuzumab deruxtecan (T-DXd) has transformed the treatment landscape of human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC), with significant improvements in survival reported in clinical trials. However, limited data exist regarding its performance in real-world settings, particularly in lower-middle-income countries (LMICs). Objectives: To evaluate the real-world effectiveness and safety of T-DXd in patients with HER2+ mBC in Türkiye. Design: A multicenter retrospective cohort study. Methods: This multicenter, retrospective cohort study, conducted by the Turkish Oncology Group, evaluated the real-world outcomes and tolerability of T-DXd in patients with HER2+ mBC across 27 oncology centers in Türkiye. The primary endpoints were real-world progression-free survival (rwPFS) and overall survival (rwOS). Secondary endpoints included response rate, safety (with adverse events (AEs) graded according to CTCAE v5.0), and evaluation of the first post-T-DXd treatments. Results: A total of 269 patients were included. The median age was 49 years (interquartile range: 42–59), and the median follow-up was 12.9 months. The median rwPFS was 17.9 months (95% confidence interval: 13.3–22.5), and the median rwOS was 35.7 months (95% confidence interval: 27.8–43.6). The objective response rate was 71.4%, and the disease control rate was 95.2%. Patients receiving T-DXd in the second line experienced significantly longer rwPFS compared with those treated in later lines ( p < 0.001). Treatment-related AEs of any grade occurred in 68.4% of patients. Interstitial lung disease was reported in 21 patients (7.8%), with 4 cases being grade ⩾3. Conclusion: In this large national real-world cohort from an LMIC, T-DXd demonstrated robust antitumor activity and a manageable safety profile in patients with HER2+ mBC. These findings are consistent with prior clinical trial data and support the applicability of T-DXd in broader clinical settings.