Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression

Abstract

Background: Among women, breast cancer (BC) is the leading cancer and the most common cause of cancer-related death between 30 and 69 years. Although lifestyle and diet are considered to have a role in global BC incidence pattern, the specific influence of dyslipidemia in BC onset and progression is not yet completely understood.

Methods: Fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) was prospectively assessed in 244 women with BC who were enrolled according to pre-set inclusion criteria: diagnosis of non-hereditary invasive ductal carcinoma; selection for surgery as first treatment, and no history of treatment with lipid-lowering or anti-diabetic drugs in the previous year. Pathological and clinical follow-up data were recorded for further inclusion in the statistical analysis.

Results: Univariate associations show that BC patients with higher levels of LDL-C at diagnosis have tumors that are larger, with higher differentiation grade, higher proliferative rate (assessed by Ki67 immunostaining), are more frequently Her2-neu positive and are diagnosed in more advanced stages. Cox regression model for disease-free survival (DFS), adjusted to tumor T and N stages of TNM classification, and immunohistochemical subtypes, revealed that high LDL-C at diagnosis is associated with poor DFS. At 25 months of follow up, DFS is 12% higher in BC patients within the third LDL-C tertile compared to those in the first tertile.

Conclusions: This is a prospective study where LDL-C levels, at diagnosis, emerge as a prognostic factor; and this parameter can be useful in the identification and follow-up of high-risk groups. Our results further support a possible role for systemic cholesterol in BC progression and show that cholesterol metabolism may be an important therapeutic target in BC patients.

Figure 1

Tumor characteristics in LDL-C tertiles groups. A. Tumor size increases across LDL-C tertiles groups. Line represents the median value of tumor size in each LDL-C tertile. B. Frequency of tumor characteristics in LDL-C tertiles groups. ^*1LDL T1-T2 (Her2-neu positive15,5%) vs LDL T3 (Her2-neu positive 27,8%): OR 5,015 (1,678-14,988) P 0,002. ^*2LDL T1 (Stage II-III 54,9%) vs LDL T2-T3 (Stage II-III 69,6%): OR 0,543 (0,313-0,943) P 0,029. Kruskall-Wallis test. ER: Estrogen Receptor; PR: Progesterone Receptor; LVI: Lymphovascular Invasion; LN: Lymph Nodes.

Figure 2

Overall and disease-free survival in LDL-C tertiles groups. Kaplan–Meier Curves. A. At 25 months, overall survival is 100% in LDL T1, 92,8% in LDL T2 and 97,2% in LDL T3 (Log rank test P 0,066). B. At 25 months, disease-free survival is 100% in LDL T1, 90,6% in LDL T2 and 88,3% in LDL T3 (Log rank test 0,013).