This study identified the relationship between RC levels and prognosis in women with breast cancer. We found that higher RC levels were associated with a higher risk of death. In addition, we performed IPTW-adjusted Kaplan-Meier analyses and IPTW-adjusted Cox regression analyses to evaluate the prognostic role of CR, and the results showed that CR was still a prognostic factor. After excluding patients with underlying diseases or those with a survival period < 1 year, RC can stably predict the risk of death in patients with breast cancer.

Breast cancer is a complex disease, and its occurrence and development involve the interaction of multiple genetic, hormonal, and lifestyle factors [15]. Studies have shown that high cholesterol levels increase the risk of breast, colorectal, and other cancers [3, 16, 17]. In addition, studies have shown that abnormal cholesterol levels are associated with the degree of malignancy and a poor prognosis in patients [3]. Cholesterol is a lipid with several important functions in the body, including the construction of cell membranes, hormone synthesis, and absorption of fat-soluble vitamins in the digestive system [18]. Dysregulation of cholesterol homeostasis is a feature of many diseases, including pathological conditions, tumours, metabolic disorders, and atherosclerosis [19].

Studies have shown that cholesterol increases the proliferation of oestrogen receptor–positive breast cancer cells via the metabolite 27-hydroxycholesterol, a molecule with selective oestrogen receptor modulatory activity [5, 10], whose levels are elevated in breast tumour biopsies compared to those in normal breast tissue [20]. In addition, dyslipidaemia leads to increased cholesterol content in cell membranes, affecting membrane fluidity and subsequent signalling [21]. Most current research has focused on total cholesterol, HDL, LDL, and triglycerides. RC is a lipoprotein residue involved in different stages of triacylglycerol degradation or lipoprotein conversion [14]. This value is the sum of the cholesterol levels in all triacylglycerol-rich lipoproteins, and its concentration is related to the degree of obesity and genetic polymorphisms and is highly correlated. Recently, with the application of statins, the focus of research has gradually shifted towards triacylglycerol-rich lipoproteins.

Previous studies on RC have focused mostly on cardiovascular and cerebrovascular diseases, diabetes, and other metabolic disorders [22, 23]. This study is the first to comprehensively evaluate the relationship between RC and survival in women breast cancer. The RCS and COX regression analyses suggested that RC was significantly and positively correlated with the risk of death in patients with breast cancer. Previous studies have reported that breast cancer is closely correlated with obesity, diabetes, hypertension, and other metabolic diseases [24]. Metabolic disorders may lead to imbalances in the synthesis and degradation of fatty acids, abnormal oestrogen synthesis and metabolism, and abnormal energy metabolism pathways in cells, thereby affecting the development and prognosis of breast cancer [21, 25]. In addition, metabolic disorders in the body can lead to insulin resistance, which, in turn, affects the development of breast cancer by promoting the insulin-like growth factor pathway [9].

Although the results of this study support the prognostic role of RC in women patients with breast cancer, the exact mechanism by which high RC levels are associated with poor survival outcomes remains uncertain. Our findings suggest that women aged ≥ 50 years have greater RC levels, which may be related to changes in hormone levels before and after menopause. Cholesterol is a precursor of androgens and oestrogens, which are closely associated with the occurrence and development of breast cancer [26]. Cholesterol metabolism interacts with hormones, affecting breast cancer cells [27, 28].

Patients with a higher BMI had greater RC levels. Some studies have shown that obesity may affect cholesterol synthesis, metabolism, and transport pathways [7, 8]. In obesity, the adipose tissue produces inflammatory factors, resulting in a chronic inflammatory state [29]. This inflammatory state may promote the development of breast cancer by activating pathways, including cell proliferation, invasion, and angiogenesis. In addition, abnormal cholesterol levels are strongly linked to metabolic syndrome, which is often associated with obesity [7]. Metabolic syndrome includes high blood pressure, high blood sugar, high cholesterol, and central obesity, among others, and the interaction of these factors may increase the risk of cardiovascular disease and diabetes [30]. Patients with higher tumour stages tended to have higher RC levels, possibly related to their overall metabolic disorders.

The relationship between breast cancer and cholesterol metabolism is complex, diverse, and involves multiple molecular pathways and biological processes. An in-depth study of the interaction between breast cancer and cholesterol metabolism will help better understand the mechanism, development process, and formulation of treatment strategies for breast cancer. It also provides a potential direction for identifying new therapeutic targets and intervention pathways.

Breast cancer is a highly heterogeneous disease, patients may have different biological characteristics and metabolic states. Monitoring RC levels can detect potentially high-risk patients earlier to enable more active interventions and reduce the risk of disease recurrence and progression, thereby improving the pertinence and effectiveness of treatment and realising individualised treatment. In addition, RC detection is non-invasive, simple, objective, and easy to implement. During the diagnosis and treatment of patients with breast cancer, repeated and dynamic assessments can be performed to avoid ineffective antitumour treatment and limited survival benefits and to maximise cost-effectiveness.

This study had several limitations. First, the study population comprised only Chinese patients. Considering the racial differences, the results of this study need to be verified in a larger study with a different population. It is worth noting that the proportion of people who received radiotherapy in this study was low, which may be due to the large differences in the utilization of radiotherapy for different tumour types in China. Head and neck cancers are more commonly treated with radiation; however, other types, such as breast cancer, tend to have lower rates of use. Second, the RC level was assessed only at baseline, and the relationship between its dynamic changes and patient prognosis could not be determined. Third, this study lacks data on molecular typing of patients, endocrine therapy and anti-HER-2 therapy, we plan to conduct further data improvement in the future. Forth, the database did not stratify surgery as upfront or after neoadjuvant, or chemotherapy as neoadjuvant or adjuvant. This is relevant since the change from clinical to pathological staging can impact the prognostic value obtained in adjusted analyses. Furthermore, the dataset lacks information on breast cancer mortality and mortality due to causes other than breast cancer in our study. We plan to improve the data collection in the future. In addition, we need to further explore the molecular mechanisms underlying RC metabolism to better screen for risk groups with poor prognoses.