Clinicopathological and Prognostic Implications of Circulating MicroRNA-429 in Breast Cancer Patients

MicroRNA-429 (miR-429), a member of the miR-200 family, has been implicated in epithelial-mesenchymal transition and tumor progression, yet its clinicopathological significance in breast cancer remains unclear. This study aimed to evaluate serum miR-429 expression in treatment-naïve breast cancer patients and correlate its levels with detailed histopathological variables, molecular subtype, treatment response, and outcome.

In this prospective study, serum samples from 49 invasive ductal carcinoma (IDC- no special type [NST]) patients and 49 age-matched healthy controls were analyzed by quantitative real-time polymerase chain reaction. Clinicopathological data (tumor grade, receptor status, lymphovascular invasion [LVI], nodal status, mitosis, tumor-infiltrating lymphocytes, necrosis, and subtype) and treatment response (Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) were recorded. Resection specimens were evaluated for residual cancer burden (RCB).

Mean serum miR-429 levels were significantly lower in cases than controls (0.92 ± 0.53 vs. 1.24 ± 0.55; t = 2.892, P = 0.005). Receiver operating characteristic analysis showed an area under the curve of 0.649 (95% confidence interval: 0.540-0.758; P = 0.011) with 67.3% sensitivity and specificity at a cut-off of <1.005. Higher miR-429 expression was significantly associated with LVI (37.5% vs. 0%, P = 0.021). Trends toward higher mitotic activity (≥6 mitoses/10 hpf: 62.5% vs. 25.0%, P = 0.094) and greater nodal involvement (50.0% vs. 20.0%, P = 0.096) were noted in the high-expression group. No significant associations were observed with grade (P = 0.190), receptor status (estrogen receptor P = 0.354; progesterone receptor P = 0.614; HER2 P = 0.579), molecular subtype (P = 0.852), RCB (P = 0.418), or RECIST response (P = 0.627). At follow-up, 42 patients (85.7%) were doing well, 5 (10.2%) had died, and outcomes were not significantly related to miR-429 (P = 0.351).

Serum miR-429 is downregulated in breast cancer and correlates significantly with LVI, suggesting a role in invasive biology. While diagnostic utility is modest, its integration into multi-microRNA panels may enhance predictive accuracy. Larger, multi-institutional, subtype-stratified studies are needed for validation.