Fan Li,1,* Chuan-Guo Chen,2,* Jiao-Fei Wei,1,3 Jia-Wen Lin,4 Zi-Ang Dou,3,4 Jun Shen,1 Shu-Qin Li1,3,4 

1Department of Breast Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of General Surgery, Nanjing Meishan Hospital, Nanjing, Jiangsu, People’s Republic of China; 3Department of Clinical Medicine, Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 4Department of clinical medicine, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jun Shen; Shu-Qin Li, Department of Breast Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, No. 6 Zhenhua East Road, High-tech Square, Lianyungang, Jiangsu Province, 222002, People’s Republic of China, Tel +861896132532 ; +8618961325781, Email shenjun2257@126.com; shuqinlilsh@126.com

Objective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR).
Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan–Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes.
Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06– 6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66– 3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR.
Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.

Keywords: breast cancer, NACT, neoadjuvant chemotherapy, non-pCR, non-pathologic complete response, reg IV, risk factor