Background/Objectives: Extrapulmonary neuroendocrine carcinomas (EP-NECs) are rare, aggressive malignancies with no standardized treatment approach. Although platinum-based chemotherapy is considered the first-line therapy, overall survival (OS) and progression-free survival (PFS) remain limited. This study aims to evaluate the clinical and pathological characteristics of EP-NEC patients, their treatment responses, and survival outcomes. Methods: This retrospective observational study included 29 EP-NEC patients diagnosed and followed between 2015 and 2024. Clinical and demographic data, tumor localization, disease stage, administered treatments, and survival outcomes were analyzed. Kaplan–Meier survival analysis was used to assess OS and PFS, with subgroup comparisons performed via the log-rank test. Results: The most common primary tumor sites were the pancreas (21%), prostate (17%), and cervix (14%). At diagnosis, 55.2% of patients had metastatic disease. First-line platinum-based chemotherapy achieved an objective response rate of 82.1%, with a median PFS of 8.16 months and a median OS of 14.16 months. Surgical intervention significantly improved survival (p = 0.020), while a high Ki-67 proliferation index (>80%) was associated with worse PFS (p = 0.032). Other factors, including smoking status and liver-directed therapies, had no significant impact on survival. Conclusions: EP-NECs present with a poor prognosis despite platinum-based chemotherapy achieving high response rates. Surgical resection improves survival outcomes, whereas high Ki-67 expression is associated with a worse prognosis. These findings highlight the need for further research into novel therapeutic strategies for EP-NECs.
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/Objectives: Sacituzumab govitecan (SG) is an antibody–drug conjugate targeting Trop-2, approved for use in metastatic triple-negative breast cancer (mTNBC) and more recently in the hormone receptor-positive/HER2-negative (mHRPBC) subtype. While clinical trials have demonstrated its efficacy, real-world data—especially those involving both molecular subtypes—remain scarce. This multicenter, retrospective study aimed to evaluate real-world observational data describing the clinical outcomes, safety, and prognostic factors associated with SG treatment in patients with mTNBC or mHRPBC. Methods: A total of 68 patients treated with SG between 2022 and 2025 were included from multiple oncology centers in Turkey. Patients with mTNBC were required to have received at least one prior chemotherapy line, while mHRPBC patients had received at least two prior chemotherapy lines in addition to cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6) plus hormone therapy. The clinical outcomes—including the progression-free survival (PFS), overall survival (OS), and objective response rate (ORR)—were evaluated. Univariate and multivariate analyses were performed to identify factors influencing outcomes. Adverse events (AEs) were also documented and graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5.0). Results: The cohort included 35 (51.5%) mTNBC and 33 (48.5%) mHRPBC patients. The median PFS was 6.1 months, and the median OS was 12.5 months, with no significant differences between subtypes. The ORR was 52.9%, with a complete response observed in 10.3% of patients. A high Eastern Cooperative Oncology Group Performance Status (ECOG PS) and liver metastasis were independent predictors of poorer PFS and OS. Prior immunotherapy did not negatively impact SG’s efficacy. SG was generally well tolerated; the most common AEs were alopecia, anemia, neutropenia, and diarrhea. Treatment discontinuation due to AEs was rare (2.9%). Conclusions: SG was associated with similar clinical outcomes and tolerability in both the mTNBC and mHRPBC subtypes. Although the real-world PFS and OS outcomes mirror those seen in clinical trials, the absence of a control group means that these findings should be interpreted descriptively rather than as confirmation of treatment efficacy. Importantly, this study provides one of the first real-world datasets evaluating SG in the mHRPBC subgroup, highlighting its potential role beyond clinical trials. These results support SG as a valuable therapeutic option in heavily pretreated patients, warranting further prospective and biomarker-driven studies.
Background/Objectives: Sacituzumab govitecan (SG) is an antibody-drug conjugate targeting Trop-2, approved for use in metastatic triple-negative breast cancer (mTNBC) and more recently in hormone receptor-positive/HER2-negative (mHRPBC) subtypes. While clinical trials have demonstrated its efficacy, real-world da-ta—especially involving both molecular subtypes—remain scarce. This multicenter, retrospective study aimed to evaluate the real-life effectiveness, safety, and prognostic factors associated with SG treatment in patients with both mTNBC and mHRPBC. Methods: A total of 68 patients treated with SG between 2022 and 2025 were included from multiple oncology centers in Turkey. Patients with mTNBC were required to have received at least one prior chemotherapy line, while mHRPBC patients had received at least two prior chemotherapy lines in addition to hormone therapy. Clinical out-comes—including progression-free survival (PFS), overall survival (OS), and objective response rate (ORR)—were evaluated. Univariate and multivariate analyses were performed to identify factors influencing outcomes. Adverse events (AEs) were also documented and graded according to NCI-CTCAE v5.0. Results: The cohort included 35 (51.5%) mTNBC and 33 (48.5%) mHRPBC patients. The median PFS was 6.1 months, and the median OS was 12.5 months, with no significant differences between subtypes. The ORR was 52.9%, with a complete response observed in 10.3% of patients. Eastern cooperative oncology group performance status (ECOG PS) and liver metastasis were independent predictors of poorer PFS and OS. Prior immunotherapy did not negatively impact SG efficacy. SG was generally well tolerated; the most common AEs were alo-pecia, anemia, neutropenia, and diarrhea. Treatment discontinuation due to AEs was rare (2.9%). Conclusions: SG demonstrated comparable effectiveness and a managea-ble safety profile in real-world patients with both mTNBC and mHRPBC. Importantly, this study provides one of the first real-world datasets evaluating SG in the mHRPBC subgroup, highlighting its potential role beyond clinical trials. These results support SG as a valuable therapeutic option in heavily pretreated patients, warranting further prospective and biomarker-driven studies.
Background/Objectives: The goal of this study is to characterize the survival patterns and outcomes of women with early-stage breast cancer, with a particular emphasis on the distinction between HER2-low and HER2-zero expression. There is limited real-world data on how patients with HER2-negative or HER2-low metastatic or recurrent breast cancer are treated. Methods: We retrospectively analyzed the medical records of 1500 breast cancer patients diagnosed between January 2020 and December 2024. From this cohort, 99 patients with HER2-low and 34 patients with HER2-zero early-stage breast cancer were included in our analysis. HER2 low was defined as Immunohistochemistry (IHC) 1+ or IHC 2+ with negative Silver In situ Hybridization (SISH), while HER2 zero was defined as IHC 0. Statistical analyses, including Kaplan–Meier survival analyses and log-rank tests for group comparisons, were performed using IBM SPSS Statistics. Results: The median age of patients was 55 years. The HER2-zero group exhibited a higher incidence of brain, liver, bone, and lung metastases (p < 0.001 for all) and increased use of CDK4/6 inhibitors (p < 0.001). In univariate analyses, younger age, an HER2-zero status, and the absence of metastases were associated with improved disease-free survival (DFS) and overall survival (OS). However, in multivariate analyses, an HER2-zero status independently predicted longer DFS (HR = 0.14, 95% CI: 0.05–0.41, p < 0.001) and OS (HR = 0.16, 95% CI: 0.042–0.6, p = 0.007). Conclusions: Our study revealed distinct metastatic patterns and survival outcomes between HER2-low and HER2-zero early-stage breast cancers. Despite a higher metastatic burden in univariate analyses, HER2 zero status was independently associated with longer DFS and OS in multivariate analyses, highlighting their biological heterogeneity and the need for further research to inform tailored strategies.
Amaç: Çalışmamızda, torasik bölgeye radyoterapi (TRT)/ kemoradyoterapi (KRT) +/- immünoterapi (İO) alan hastalarda gelişen radyasyon pnömoniti sürecini ve etki eden faktörlerin ortaya konulması amaçlanmıştır. Yöntem: TRT alan hastaların verileri retrospektif olarak tarandı ve radyasyon pnömoniti gelişen 26 hastanın verileri analiz edildi. Bulgular: Hastaların ortanca yaşı 54.5 iken çoğu erkekti. Hastaların çoğunluğunda primer tanı akciğer kanseri idi. Ondört hasta (%53.8) eş zamalı KRT alırken, 13 hasta (%50) IO ile eş zamanlı RT almıştı. Toplamda ise 17 hasta (%65.4) tedavi sürecinde IO almıştı. Median RT dozu 44 Gy idi. Hastalarda RT ile pnömonit gelişene kadar geçen süre ortanca 5.8 ay iken IO başlangıcından pnömonitis gelişene kadar geçen süre ortanca 6.2 aydı. 20 hastada (%76.9) grad 2, 3 hastada (%11.5) grad 3 ve 3 hastada (%11.5) grad 1 pnömonitis görülmüştü. En sık görülen tomografi bulguları konsolidasyon ve septal kalınlaşma ve distorsiyon ile 5 hastada retikülonodüler görünüm ve 3 hastada buzlu cam görünümü şeklindeydi. Ortanca steroid kullanımı 1.95 ay idi . 14 hastada (%53.8) steroid dozu 1 mg/kg dozuna kadar çıkılmıştı. Ortanca 22.5 aylık takip süresinde, ortanca PFS 28.8 ay ve ortanca OS 54.1 aydı. Hiçbir hastada RT pnömonitine bağlı ölüm gözlenmedi. Grad 2-3 RT pnömoniti gelişimine etki eden faktörlerin analizi yapıldığında, her hangi bir predikte edici anlamlı faktör gösterilemedi. Sonuç: Çalışmamızda KRT+İO alan hastalarda RT pnömoniti İO almayanlara kıyasla daha fazla görülmedi. Fakat hasta sayısı az olduğu için daha fazla hasta sayıları ile geniş kapsamlı karşılaştırmalı çalışmalara ihtiyaç bulunmaktadır. RT pnömoniti zamanında akla getirilmediğinde ciddi mortal olabilen fakat erken farkedilerek, doğru tedavi edildiğinde yönetilebilir bir klinik antitedir.