Abstract 【Background】 Lipid metabolism is one of the most conspicuous metabolic changes in malignant tumors. Previous studies confirmed that higher levels of “adverse lipids” might lead to poor outcomes and lipid-lowering drugs could act as a protective role in improving the prognosis of breast cancer patients. Nevertheless, few studies have clarified the impact of serum lipid levels and their changes on the tumor prognosis. Particularly for breast cancer patients treated with neoadjuvant chemotherapy, little has been studied whether their lipid levels or changes during neoadjuvant chemotherapy can serve as a valid prognostic factor. 【Methods】This study enrolled patients who received surgical treatment after neoadjuvant chemotherapy in Renji Hospital from March 2016 to December 2020. Patients were included if they were female aged 18 years or older; had pathologically confirmed unilateral invasive breast cancer; had tumor of at least 2cm in size without distant metastasis (T1-4, N0-3, M0); and underwent radical surgery for breast cancer successfully after neoadjuvant chemotherapy. We retrospectively gathered the baseline clinicopathological information and lipid metabolism-related biomarkers from electronic medical records. The study endpoints were disease free survival (DFS), overall survival (OS), relapse free survival (RFS), distance recurrence free survival (DRFS), and local recurrence free survival (LRFS). The prognostic value of each lipid levels and their variation levels were systematically evaluated and the importance of lipid biomarkers were ranked by Random Forest. 【Results】 The baseline clinicopathological information and lipid metabolism biomarkers were available from 200 eligible patients. As of the last follow-up in March 2023, 11 patients died, 24 experienced DFS events and 20 underwent RFS events. It showed no significant correlations of lipid levels before (baseline) and after (preoperative) neoadjuvant chemotherapy with any survival outcome. However, we found that the relative increase of low-density lipoprotein (LDL) led to poorer DFS (P=0.003), RFS (P=0.01), DRFS (P=0.01), and LRFS (P=0.0039), meanwhile the relative increase of total cholesterol (TC) and non-high-density lipoprotein (NHDL) during neoadjuvant period was significantly related to the worse prognosis (TC, DFS P=0.0084; NHDL, DFS P=0.031, RFS P=0.009) as well. After adjusted by multiple factors, the adverse impacts of increasing TC (DFS P=0.005; RFS P=0.026), LDL (DFS P=0.004; RFS P=0.006) and NHDL (DFS P=0.032; RFS P=0.014) on DFS or RFS were still maintained. The results of Random Forest revealed that LDL changes and Body Mass Index (BMI) ranked higher in terms of predicting survival outcomes. Based on these data, BMI >25.4 kg/m2 or LDL elevation >0.54 mmol/L were defined as High-risk Lipid Metabolism (HLM), while BMI ≤ 25.4 kg/m2 and LDL elevation ≤ 0.54 mmol/L were regarded as Low-risk Lipid Metabolism (LLM). Compared to LLM, HLM had a worse OS (P=0.026), DFS (P=0.0011) and RFS (P=0.0011). 【Conclusion】Our study demonstrated that the relative elevation of LDL, TC and NHDL levels during neoadjuvant chemotherapy is an independent prognostic risk factor for breast cancer patients. It was also the first time to propose the concept of high-risk lipid metabolism (HLM). 【keywords】Breast cancer, Lipid metabolism, Low-density lipoprotein (LDL), Body Mass Index (BMI), Prognosis. Citation Format: Xinru Chen, Wenjin Yin, Yingying Zhao, Jinsong Lu. Prognostic value of serum lipid levels in breast cancer patients who received neoadjuvant chemotherapy: A retrospective exploratory analysis of the prospective cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-08.
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