Analysis of Factors Related to Lymph Node Metastasis Following Neoadjuvant Chemotherapy for Breast Cancer: Correlation Between Plasma Exosomal Circular RNA and Metastasis

Sushuang Ma,1 Yanqiu Huang,2 Qingyan Yang,1 Xiaoyan Liu,1 Zhiqiang Zhang,1 Bing Yan1 1Department of Breast Surgery, Affiliated Hospital of Hebei Engineering University, Handan, Hebei, 056002, People’s Republic of China; 2Big Data Center, Affiliated Hospital of Hebei Engineering University, Handan, Hebei, 056002, People’s Republic of ChinaCorrespondence: Bing Yan, Department of Breast Surgery, Affiliated Hospital of Hebei Engineering University, No. 81, Congtai Road, Congtai District, Handan, Hebei, 056002, People’s Republic of China, Tel +86 17320662026, Email [email protected]: To investigate the correlation between plasma exosomal circular RNA (circRNA) (non-invasive, dynamically monitorable) and lymph node metastasis following neoadjuvant chemotherapy in breast cancer and highlight its predictive superiority over traditional serum markers.Methods: The clinicopathological data and follow-up data of 487 patients with breast cancer who received neoadjuvant therapy in our hospital between 1 January 2018 and 1 January 2020 were retrospectively collected using convenience sampling. Following screening, 379 patients who met the inclusion and exclusion criteria were included in the analysis. The patients’ data, including age, clinical TNM stage, tumour pathological type, tumour histological grade, tumour molecular typing, neoadjuvant regimen and course of treatment, were collected for analysis.Results: Log rank test results showed that there were significant differences between the two groups in molecular typing (χ2 = 46.058, P < 0.001), neoadjuvant regimen (χ2 = 10.996, P < 0.001), axillary surgery (χ2 = 4.267, P = 0.039), histological grade (χ2 = 32.280, P < 0.001) and pathological complete response (pCR) (χ2 = 18.993, P < 0.001). The t-test results showed that the circRNA level was higher in the metastatic group than in the non-metastatic group (8.55 ± 2.12 vs 3.70 ± 1.81, t = 22.868, P < 0.001). The results of regression analysis showed that non-pCR (odds ratio [OR] = 2.320, 95% CI: 1.259– 4.276), molecular subtype HER2+ (OR = 1.747, 95% CI: 1.070– 2.852), histological grade II (OR = 3.159, 95% CI: 1.537– 6.491), histological grade III (OR = 2.606, 95% CI: 1.242– 5.466) and circRNA expression level (OR = 1.497, 95% CI: 1.398– 1.602) were risk factors for postoperative metastasis in patients with breast cancer. The level of circRNA has predictive value for the occurrence of postoperative metastasis in breast cancer. The area under the curve was 0.955 (95% CI: 0.933– 0.976), with a sensitivity of 87.4% and a specificity of 91.9%.Conclusion: Molecular typing, pCR status, histological grade and plasma exosomal circRNA expression level are independent predictors of recurrence and metastasis following neoadjuvant therapy. Notably, plasma exosomal circRNA, with its non-invasive and dynamic monitoring advantages, shows promising predictive potential for lymph node metastasis, providing a novel and superior clinical tool for prognosis assessment.Keywords: breast cancer, neoadjuvant treatment, prognosis, circular RNA