Abstract
BackgroundHigh triglycerides and low levels of high density lipoprotein (HDL)-cholesterol are observed to promote tumor growth. However, whether breast cancer heterogeneity may explain the contradictory influence of triglycerides and cholesterol observed on breast cancer prognosis remains unclear.MethodsA population-based survival study among 464 breast cancer cases identified within the Tromsø study was conducted. Pre-diagnostic triglycerides, total-cholesterol and HDL-cholesterol were measured, and detailed clinical and histopathological data were obtained. Using tissue microarray, all breast cancer cases were reclassified into the following subtypes: Luminal A, Luminal B, HER2-enriched, and triple negative breast cancer (TNBC). Multivariable Cox proportional hazards regression models were used to study the associations between pre-diagnostic lipids and breast cancer recurrence, mortality, and survival.ResultsA total of 464 breast cancer patients, with mean age at diagnosis of 57.9 years, were followed for a mean 8.4 years. TNBC patients in the highest tertile of triglycerides (≥ 1.23 mmol/l) had 3 times higher overall mortality compared to TNBC patients in the lowest tertile (≤ 0.82 mmol/l) (HR 2.99, 95% CI 1.17–7.63), and the 5-year overall survival was 19% lower for TNBC patients in the highest vs. lowest tertile of triglycerides (65% vs. 84%). TNBC patients in the highest tertile of the HDL-cholesterol/total-cholesterol ratio (≥0.35), compared to those in the lowest tertile (≤0.27), had a 67% reduced overall mortality risk (HR 0.33, 95% CI 0.12–0.89). No associations were observed between lipids and prognostic outcome among breast cancer patients overall, or among patients with luminal A and luminal B subtypes. Among HER2-enriched patients, pre-diagnostic triglyceride level was inversely associated with overall mortality.ConclusionOur study suggests that pre-diagnostic triglycerides and the HDL-cholesterol/total-cholesterol ratio may independently provide unique information regarding prognostic outcome among triple negative breast cancer patients. However, a small sample size underlines the need for additional studies.
Highlights
High triglycerides and low levels of high density lipoprotein (HDL)-cholesterol are observed to promote tumor growth
Different lipoprotein subfractions vary by progesterone receptor expression [29], suggesting the influence of HDL-cholesterol on breast cancer prognosis may differ by breast cancer phenotype [30]
Observations in the present study extend previous observations linking variation in pre-diagnostic serum lipids, and in particular triglycerides, to breast cancer prognosis by molecular subtypes
Summary
High triglycerides and low levels of high density lipoprotein (HDL)-cholesterol are observed to promote tumor growth. Whether breast cancer heterogeneity may explain the contradictory influence of triglycerides and cholesterol observed on breast cancer prognosis remains unclear. Studies investigating the influence of metabolic differences on breast cancer prognosis often show contradictory results, and information on breast cancer heterogeneity/subtypes is not included [1,2,3,4]. Previous studies have shown inconsistent results on pre-diagnostic obesity and TNBC prognosis [18, 19], suggesting there may be other metabolic mechanisms driving the carcinogenesis in more aggressive tumors. High density lipoprotein (HDL)-cholesterol possesses anti-inflammatory properties [24], and has been inversely associated with breast cancer risk [25], and suggestively breast cancer survival [22]. Different lipoprotein subfractions vary by progesterone receptor expression [29], suggesting the influence of HDL-cholesterol on breast cancer prognosis may differ by breast cancer phenotype [30]
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