Evaluation of Longitudinal CD40 and CD40L Changes During Adjuvant Breast Cancer Therapy and Their Association with Left Ventricular Dysfunction

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Background: Left ventricular (LV) dysfunction is a clinically important complication of anthracycline- and trastuzumab-based treatment in breast cancer. Inflammatory pathways may contribute to cancer therapy-related cardiac dysfunction, and the CD40/CD40 ligand (CD40L) axis has been implicated in vascular inflammation and myocardial injury. This study assessed longitudinal changes in CD40 and CD40L during adjuvant treatment and their association with LV dysfunction. Methods: Twenty-eight women with operable breast cancer receiving adjuvant anthracycline-based chemotherapy with or without trastuzumab were prospectively evaluated. Blood samples were collected at baseline, 6 months, and treatment completion at 15 months to measure CD40 and CD40L. Cardiac function was assessed by transthoracic echocardiography, including left ventricular ejection fraction and global longitudinal strain, at baseline and every 3 months. Repeated-measures analysis of variance examined temporal biomarker changes and interactions with LV dysfunction. Results: Participants had a mean age of 52.6 ± 10.7 years and a mean BMI of 25.8 ± 4.8 kg/m2; 64% were postmenopausal, 76% had HER2-positive disease, and 79.3% received radiotherapy and trastuzumab. During follow-up, 15 patients (53.6%) developed LV dysfunction. CD40 levels remained stable overall (p = 0.31), whereas CD40L increased significantly over time (p < 0.001). Baseline CD40 did not differ by LV dysfunction status (p = 0.79). However, CD40 showed a significant time-by-LV dysfunction interaction (p = 0.022), increasing late in patients with LV dysfunction and declining in those without it. CD40L showed no such interaction (p = 0.85). Conclusions: In this small exploratory cohort, CD40 demonstrated differential longitudinal patterns according to subsequent LV dysfunction, whereas CD40L increased over time without a clear association with LV dysfunction. These findings should be interpreted as hypothesis-generating and require validation in larger prospective cohorts.

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