Association of CDK4 Expression with Histopathological Grade and Metastasis in Luminal Breast Cancer: A Cross-Sectional Study

Abstract

Background: The luminal (hormone receptor–positive/HER2–negative) subtype constitutes the majority of breast cancer cases. Despite a generally favorable prognosis, a significant proportion of patients experience metastasis. Cyclin-dependent kinase 4 (CDK4) is a key regulator of the cell cycle, and its dysregulation is a known driver of uncontrolled proliferation in luminal breast cancer. However, data on its association with adverse pathological features in the Indonesian population are limited. This study aimed to investigate the association between CDK4 expression, histopathological grade, and metastatic status in patients with luminal subtype breast cancer in Makassar, Indonesia. Methods: This cross-sectional study included 74 patients with luminal subtype breast cancer. CDK4 expression in formalin-fixed, paraffin-embedded tumor tissues was assessed via immunohistochemistry and categorized as high or low. The association between CDK4 expression, histopathological grade, and metastatic status was evaluated using the χ2 test. Binary logistic regression was performed to calculate the odds ratio (OR) for metastasis. Results: Of the 74 patients, 29 (39.2%) had metastatic disease. High CDK4 expression was significantly associated with high-grade tumors (P = 0.02) and with the presence of metastasis (P = 0.04). Patients with high CDK4 expression had 1.86 times higher odds of having metastasis compared with those with low CDK4 expression (OR, 1.86; 95% CI, 1.03–3.38). Conclusion: Overexpression of CDK4 in luminal subtype breast cancer is significantly associated with higher histopathological grade and an increased likelihood of distant metastasis. This suggests CDK4 is a marker of more aggressive tumor biology and a potential prognostic marker in this patient population, warranting further investigation in longitudinal studies.

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