Abstract
BackgroundComprehensive investigations of the associations between 21-gene recurrence assay and metabolic profiles in Chinese breast cancer patients are limited.MethodsWe evaluated the relations of the 21-gene recurrence risk score (RS) and the expression of cancer-related genes with metabolic factors and biomarkers of insulin and the insulin-like growth factor (IGF) axis, and examined the interactions between the 21-gene RS and these metabolic profiles on breast cancer recurrence in Chinese women with HR-positive, HER2-negative early-stage breast cancer.ResultsThe 21-gene RS was inversely associated with body mass index ([BMI]β: −0.178 kg/m2; P=0.040), the homeostasis model assessment of insulin resistance index ([HOMA-IR] β: −0.031; P=0.042), insulin (β: −0.036 uIU/ml; P=0.009), and C-peptide (β: −0.021 ug/L; P=0.014) and was positively associated with high-density lipoprotein cholesterol (β: 0.025 mmol/L; P=0.004), which were driven by the relation patterns between specific cancer-related genes and these metabolic profiles. Each 10-unit increase in the 21-gene RS was associated with 28% (95% CI: 5–47%) higher risk of breast cancer recurrence; this association was also observed in patients with favorable metabolic profiles in relevant to an absence of obesity, insulin resistance, hyperglycemia, hypertension, or dyslipidemia (28–44% higher risk) and among women with a low level of insulin, C-peptide, or the IGF1/IGFBP3 ratio (41–155% higher risk).ConclusionsThe 21-gene RS was related to favorable metabolic profiles including lower BMI, HOMA-IR, insulin, and C-peptide, and higher HDL in Chinese breast cancer patients, and its prognostic impact on breast cancer recurrence was more likely to present among patients with relatively favorable metabolic profiles.
Highlights
IntroductionBreast cancer is the leading cause of cancer death in women and has surpassed lung cancer as the most commonly diagnosed cancer (approximately 11.7% of total new cancer cases) worldwide in 2020, according to statistics released by the International Agency for Research on Cancer [1]
Breast cancer is the leading cause of cancer death in women and has surpassed lung cancer as the most commonly diagnosed cancer worldwide in 2020, according to statistics released by the International Agency for Research on Cancer [1]
The 21-gene risk score (RS) was inversely associated with body mass index (BMI) (b: −0.178 kg/m2; 95% confidence intervals (CIs): −0.347 to −0.008 kg/m2) and homeostasis model assessment of insulin resistance (HOMA-IR) (b: −0.031; 95% CI: −0.347 to −0.008) and was positively associated with high-density lipoprotein (HDL) (b: 0.025 mmol/L; 95% CI: 0.008 to 0.042 mmol/L) after adjustment for age and postmenopausal status (Figure 2A)
Summary
Breast cancer is the leading cause of cancer death in women and has surpassed lung cancer as the most commonly diagnosed cancer (approximately 11.7% of total new cancer cases) worldwide in 2020, according to statistics released by the International Agency for Research on Cancer [1]. The 21-gene recurrence risk score (RS) is computed on the basis of the expression levels of these genes and has been widely used to predict the risk of distant recurrence and the potential benefit of adjuvant chemotherapy in women with ER-positive, HER2-negative early-stage breast cancer [3,4,5]. Taking into account the 21gene RS assay, as well as metabolic risk factors and circulating biomarkers, would help accurately characterize the metabolic status of breast cancer patients and identify individuals at increased risk for breast cancer recurrence. Comprehensive investigations of the associations between 21-gene recurrence assay and metabolic profiles in Chinese breast cancer patients are limited
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