Lokal ileri evredeki meme kanseri hastalarında bilişsel fonksiyonların değerlendirilmesi ve biyomarker ilişkisi
Evaluation of cognitive functions and biomarker association in patients with locally advanced breast cancer
- Tez No: 960450
- Danışmanlar: DOÇ. DR. ZEYNEP GÜLSÜM GÜÇ
- Tez Türü: Tıpta Uzmanlık
- Konular: Onkoloji, Oncology
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2025
- Dil: Türkçe
- Üniversite: İzmir Katip Çelebi Üniversitesi
- Enstitü: İzmir Atatürk Eğitim ve Araştırma Hastanesi
- Ana Bilim Dalı: İç Hastalıkları Ana Bilim Dalı
- Bilim Dalı: İç Hastalıkları Bilim Dalı
- Sayfa Sayısı: 90
Özet
Amaç: Bu tez çalışması, lokal ileri evre meme kanseri (LAEMK) tanılı kadınlarda neoadjuvan kemoterapinin bilişsel işlevler üzerindeki etkilerini ve serum nörofilament hafif zincir (NfL) düzeyleriyle olan ilişkisini incelemeyi amaçlamıştır. Yöntem:Kesitsel ve prospektif olarak planlanan bu çalışmaya İzmir Atatürk Eğitim ve Araştırma Hastanesi Onkoloji Polikliniği'nde takip edilen ve meme kanseri tanısı ile tedavi gören 61 kadın hasta dahil edilmiştir. Tüm hastalara kemoterapi öncesi ve sonrası olmak üzere iki farklı zaman noktasında Montreal Bilişsel Değerlendirme (MoCA) testi, Frontal Değerlendirme Bataryası (FAB), Depresyon Ölçeği, 5 Kelime Testi ve Saat Çizme Testi uygulanmış; Nörokognitif işlevleri biyolojik düzeyde objektif olarak değerlendirebilmek amacıyla, serum nörofilament hafif zincir (NfL) düzeyleri de her iki zaman noktasında (kemoterapi öncesi ve sonrası) çalışılmıştır. Bilişsel bozulma, MoCA'da ≥3 puan düşüş veya FAB'da ≥2 puan düşüş olarak tanımlanmıştır Elde edilen veriler SPSS programı kullanılarak analiz edilmiş, istatistiksel anlamlılık düzeyi p
Özet (Çeviri)
Aim: This thesis aimed to investigate the effects of neoadjuvant chemotherapy on cognitive functions and its relationship with serum neurofilament light chain (NfL) levels in women diagnosed with locally advanced breast cancer (LABC). Methods: This study was designed as a cross-sectional and prospective clinical investigation and included 61 female patients receiving treatment for breast cancer and followed at the Oncology Outpatient Clinic of İzmir Atatürk Training and Research Hospital. All participants underwent the Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Beck Depression Inventory, Five Word Test, and Clock Drawing Test at two time points: before and after chemotherapy. To objectively assess neurocognitive function at the biological level, serum neurofilament light chain (NfL) levels were also measured at both time points. Cognitive impairment was defined as a ≥3-point decrease in MoCA or a ≥2-point decrease in FAB scores. The data were analyzed using SPSS software, with a statistical significance threshold set at p < 0.05. Independent samples t-test, ROC analysis, and multiple linear regression were employed for statistical evaluations. Results: The mean age of the 61 participants was 51.98 years; 59% (n=36) were postmenopausal, and 41% (n=25) were premenopausal. The most frequently administered chemotherapy protocol was anthracycline + paclitaxel (n=29, 47.5%). Significant cognitive decline was observed in the post-chemotherapy period. The mean MoCA score decreased from 24.80 ± 2.45 pre-chemotherapy to 23.02 ± 2.80 post-chemotherapy (p < 0.001). Similarly, a significant decline in FAB scores was recorded (from 15.13 ± 2.05 to 13.36 ± 2.30; p < 0.001), indicating a deterioration in frontal lobe functions. No statistically significant associations were found between cognitive decline and clinical or demographic factors such as menopausal status, tumor subtype, hormone receptor status (ER/PR/HER2), tumor grade, chemotherapy protocol, educational level, or marital status. However, a marked increase in serum NfL levels was observed in patients who experienced cognitive impairment (113.85 ± 23.14 pg/mL), which was significantly higher than in patients without impairment (25.40 ± 12.29 pg/mL; p < 0.001). ROC analysis demonstrated that changes in NfL levels had excellent predictive power for cognitive impairment, with an AUC of 1.000 (p < 0.001). In multivariate regression analysis, an increase in NfL levels (β = 0.742, p < 0.001), high tumor grade (β = 1.395, p = 0.004), and progesterone receptor positivity (β = 1.110, p = 0.006) were identified as independent predictors of cognitive impairment. The model explained 61.9% of the total variance (R² = 0.619, p < 0.001). Results: The mean age of the 61 patients included in the study was 51.98 years; 59% (n = 36) were postmenopausal, and 41% (n = 25) were premenopausal. The most commonly administered chemotherapy protocol was Anthracycline + Paclitaxel (n = 29, 47.5%). The mean MoCA score was 24.80 ± 2.45 before chemotherapy and 23.02 ± 2.80 after chemotherapy; this difference was statistically significant (p < 0.001). The mean BDI score increased significantly from 12.73 ± 6.55 to 17.53 ± 7.71 after chemotherapy (p < 0.001). The change in serum NfL levels differed significantly between patients with cognitive impairment (based on MoCA) and those without. In the cognitive impairment group, the mean NfL change was 113.85 ± 23.14 pg/mL, whereas in the non-impaired group, it was 25.40 ± 12.29 pg/mL. This difference was found to be highly significant (t = -17.721, p < 0.001) according to the independent samples t-test. Post-chemotherapy NfL levels (SecondSample) also differed significantly between groups: 259.60 ± 46.70 pg/mL in the cognitive impairment group versus 118.55 ± 57.04 pg/mL in the group without impairment (t = -10.607, p < 0.001). Conclusion: This study demonstrated that neoadjuvant chemotherapy has a significantly negative impact on cognitive functions in women with locally advanced breast cancer. The significant increase in serum NfL levels observed in patients with cognitive impairment suggests that NfL may serve as an objective biomarker of chemotherapy-induced neurodegenerative changes. The findings indicate that chemotherapy-related cognitive changes can be monitored not only through clinical observation but also with biological markers such as serum NfL, thus offering valuable contributions to the field. Identifying NfL as a sensitive and early biomarker of cognitive impairment may facilitate its integration into clinical practice through future studies with larger cohorts. Monitoring cognitive functions during cancer treatment and implementing early interventions when necessary—particularly using biomarkers like NfL—may enhance patients' quality of life and support the development of personalized oncological approaches.
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