Background: Pathological complete response (pCR) following neoadjuvant therapy (NAT) is a key surrogate marker for long-term outcomes in HER2-positive breast cancer. Identifying clinical and biological predictors of pCR, including systemic inflammatory and nutritional markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-albumin ratio (NAR), C-reactive protein-to-albumin ratio (CAR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI), may help refine treatment strategies and improve patient outcomes. Methods: We retrospectively analyzed 174 patients with stage II–III HER2-positive breast cancer who received neoadjuvant anti-HER2-based regimens at multiple centers between 2010 and 2025. Demographic, clinicopathological, and laboratory data were collected, and inflammatory and nutritional indices (NLR, PLR, LMR, NAR, CAR, SII, PNI) were calculated. Predictors of pCR were evaluated using univariate and multivariate logistic regression analyses. Results: Overall, 49% of patients achieved pCR. In multivariate analysis, independent predictors of pCR were hormone receptor negativity, smaller tumor size, HER2 IHC 3+ expression, dual HER2 blockade, and a higher prognostic nutritional index (PNI ≥ 55). In contrast, systemic inflammatory indices such as NLR, PLR, LMR, NAR, CAR, and SII were not significantly associated with pCR. Conclusions: This multicenter real-world study demonstrates that conventional inflammatory markers have limited predictive value, whereas the PNI emerges as a simple and practical biomarker reflecting nutritional and immune status. Integrating PNI with clinicopathological factors may enhance risk stratification and help guide individualized neoadjuvant treatment strategies in HER2-positive breast cancer.

Background and Objectives: The prognostic significance of body mass index (BMI) in metastatic HER2-positive breast cancer (BC) remains unclear, with previous studies yielding conflicting results. This multicenter real-world study aimed to investigate the prognostic role of BMI in this patient population. Materials and Methods: A total of 169 female patients with metastatic HER2-positive BC who received trastuzumab-based treatment between 2010 and 2024 were included. Patients were categorized by BMI (<30 kg/m² vs. ≥30 kg/m²). The primary endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan–Meier and Cox regression analyses were performed overall and in subgroups stratified by hormone receptor (HR) status. Results: In the overall cohort, a BMI ≥ 30 was not significantly associated with OS or PFS. However, in the HR-positive/HER2-positive subgroup, BMI ≥ 30 kg/m² was linked to significantly shorter OS (p = 0.024) and PFS (p = 0.047) by Kaplan–Meier analysis. However, these associations did not remain statistically significant in multivariate analyses. No significant BMI-related differences were observed in the HR-negative subgroup. Other independent negative prognostic factors included recurrent disease, the presence of brain metastases, and a high Ki-67 index. Conclusions: BMI was not identified as an independent prognostic factor in the overall population. However, among HR-positive/HER2-positive patients, obesity was associated with poorer survival in univariate analysis, but this was not confirmed in multivariate analysis. These findings underscore the need for prospective studies to clarify the prognostic role of adiposity, considering biological subtypes.

Background/Objectives: Prostate cancer is a leading cause of cancer-related morbidity and mortality. While prostate-specific antigen (PSA) is crucial for monitoring, its static levels are limited in predicting outcomes precisely. The Kinetics of Elimination of PSA (KELIM PSA) has recently emerged as a dynamic biomarker of treatment response. This research sought to determine the predictive power of KELIM PSA in castration-resistant prostate cancer (CRPC) on androgen receptor pathway inhibitors (ARPI). Methods: This study retrospectively analyzed 98 CRPC patients treated with enzalutamide or abiraterone. The patients were categorized as either unfavorable (KELIM < 1) or favorable (KELIM ≥ 1). Demographic and clinical characteristics were compared, and survival outcomes were evaluated using Kaplan–Meier curves and Cox regression. Results: Of the cohort, 42 (42.9%) patients had favorable and 56 (57.1%) unfavorable KELIM values. The unfavorable group had a higher mortality rate (62.5% vs. 38.1%, p = 0.029). Univariate analysis showed that poor KELIM results increased mortality risk twofold (hazard ratio [HR]: 2.30, 95% confidence interval [CI]: 1.26–4.19, p = 0.006). In multivariable analysis, unfavorable KELIM remained independently associated with worse overall survival (HR: 2.09, 95% CI: 1.12–3.89, p = 0.020), together with second-line ARPI (HR: 3.19, 95% CI: 1.71–5.93, p < 0.001) and ADT + docetaxel during CSPC (HR: 2.14, 95% CI: 1.11–4.12, p = 0.022). Kaplan–Meier curves revealed that the unfavorable group had notably reduced overall survival and progression-free survival (log-rank p = 0.018). Conclusions: KELIM PSA is an independent predictor in ARPI-treated CRPC. By integrating PSA kinetics into prognostic models, risk stratification may be improved, and this may guide individualized treatment. Prospective multicenter validation is warranted.

To the Editor,We read with interest the study titled "Expression of miR-101-3p and its target ADAM15 gene in colorectal cancer patients" published in the Çukurova Medical Journal . The authors' study is significant in that it draws attention to the potential relationship between miR-101-3p and ADAM15 in colorectal cancer and provides a basis for hypothesis generation. The topic is relevant, particularly given the increasing interest in miRNA-mediated regulatory networks in colorectal cancer. However, we would like to bring to constructive discussion certain aspects that warrant attention regarding the article's methodology, data presentation, and interpretation.The authors used β-actin as the reference gene for normalizing both miR-101-3p and ADAM15 mRNA expression. However, the use of protein-coding mRNAs like β-actin in miRNA quantification is methodologically controversial. This is because mature miRNAs and mRNAs differ significantly in size, stability, and cDNA synthesis efficiency. In the literature, U6 snRNA, RNU48, RNU6B or reference miRNAs showing stable expression are recommended for miRNA normalization2. ΔΔCt results based on a single and inappropriate reference gene can directly affect the direction and magnitude of expression changes. Additionally, the biological effect of ADAM15 occurs at the protein level. Increased mRNA levels alone do not prove a relationship with invasion, migration, shedding activity, or metastasis. We believe that ADAM15 protein levels should be confirmed by Western blot or immunohistochemistry3.Formalin-fixed paraffin-embedded (FFPE) samples pose significant technical limitations due to RNA cross-linking and fragmentation. The authors reported the (A260-A320)/(A280-A320) > 1.8 criterion but did not provide information on RNA integrity indicators (RIN, DV200). Although miRNAs are more resistant to fragmentation compared to mRNAs, for reliable quantification of ADAM15 mRNA, the DV200 value should have been reported4.The central hypothesis of the study is that miR-101-3p suppresses ADAM15 at the post-transcriptional level. However, the presented data consist solely of expression correlation in matched tumor/normal tissues. The authors themselves acknowledge this limitation in the discussion section. Common regulatory mechanisms, such as tumor stage, cellular composition, stromal contamination, hypoxia, inflammation, or epigenetic changes, may simultaneously cause low miR-101-3p levels and high ADAM15 expression.For the biomarker claim, the relationship of miR-101-3p and ADAM15 expressions with clinicopathological parameters such as stage, location, histological type or age should be examined, and survival or response to treatment data should be provided for prognostic prediction. The study's sample size is limited to n=30 and no power analysis is provided. This number is insufficient, especially for subgroup comparisons.In the results text, the expression "2.83-fold change, 183% increase" is used for the ADAM15 fold-change value. In contrast, the title of Figure 4 states "2.28-fold," while within the figure, the value 2.82 is visualized along with "282% increase." Providing three different values in three different places creates uncertainty for the reader.We hope that these constructive criticisms will contribute to the authors and to researchers who will work in similar fields in the future. We express our respect for the effort put in by the authors.

Comment on “PARP-1 rs1136410 Polymorphism and Gastrointestinal Cancer Risk: A Meta-Analysis of Cancer-Type and Ethnic-Specific Associations” - Medeniyet Medical Journal