CDK4 Expression in Invasive Ductal Carcinoma of the Breast and its Association with Prognostic Parameters: A Cross-sectional Study

Introduction: Breast cancer is a growing public health concern in India, often diagnosed at advanced stages, leading to poor outcomes. Identifying effective biomarkers is crucial. CyclinDependent Kinase (CDK)4, a key regulator of the cell cycle, is frequently overexpressed in breast cancer, promoting tumour growth and emerging as a potential therapeutic target. Aim: To determine the expression of CDK4 marker in Invasive Ductal Carcinoma (IDC) of the breast and its association with prognostic parameters. Materials and Methods: The present cross-sectional analytical study utilised retrospective data from Sri Devaraj Urs Medical College, Kolar, Karnataka, India, utilising data spanning from January 2018 to December 2021.The study period extended over 18 months, from April 2023 to October 2024. Ninety histologically confirmed IDC breast cases were analysed, excluding recurrent cases, chemotherapy/radiotherapy-treated cases, improperly fixed specimens, male breast carcinomas and secondary metastases. Immunohistochemical analysis of CDK4 was conducted, evaluating nuclear and cytoplasmic staining separately and its association with prognostic parameters as size, grade, stage of tumour, metastatic lymphnodes, lymphovascular invasion, tumour infiltrating lymphocytes and expression of ER, PR, Her2/Neu, Ki67 in IDC breast was done. All data were entered into Microsoft Excel and analysed using Statistical Package for Social Sciences (SPSS) 22 version software. Categorical variables were presented as percentages. Associations between CDK4 expression and clinicopathological factors were tested using Chi-square test. A p-value <0.05 was considered statistically significant. Results: The study included 90 IDC cases, mean age was 52.5 years. CDK4 showed cytoplasmic positivity in 63.3% (n=57) and nuclear positivity in 47.8% (n=43). Nuclear CDK4 positivity showed significant association with HER2/Neu positivity (p=0.004), advanced stage (p<0.001), larger tumours (T3/T4) (p<0.001), presence of LVI (p=0.022), poor prognosis (p<0.001), and higher tumour grade (p<0.001). Cytoplasmic CDK4 expression showed no significant association with prognostic parameters. Conclusion: As per the present study findings nuclear CDK4 expression significantly associated with aggressive tumour characteristics and worse prognosis in breast IDC, highlighting its potential as a prognostic biomarker and therapeutic target. Cytoplasmic CDK4 expression, though frequent, had limited prognostic utility. The findings emphasize the biological importance of subcellular localisation of CDK4 in breast cancer.