Abstract

Abstract Backgound: Obesity and related metabolic imbalances, including increased activity of free fatty acids, may promote tumor growth and metastasis. Fatty acids are mainly stored as triacylglycerols. Yet, the role of serum-triglycerides on breast cancer prognosis is still undefined. Methods: A population based survival study among 575 breast cancer patients identified within the Tromsø study during 1979-2008, was conducted. Pre-diagnostic serum triglycerides, high density lipoprotein-cholesterol, total cholesterol, height and weight were measured. Histopathological and clinical data were obtained from medical records, and hormone receptor, HER2 status, and Ki-67 were re-analyzed on tissue microarray blocks. Multivariate Cox proportional Hazard regression models were used to study the associations between patient characteristics including s-triglycerides, and breast cancer survival. Results: Among 575 women with invasive breast cancer (stage 1-3), a total of 87 women were diagnosed with triple negative breast cancer (TNBC). Patients diagnosed with TNBC, compared to non-TNBC, were likely to be younger at diagnosis (55.3 vs 57.9 years, p=0.061), they had larger tumors (29.7 mm vs 22.5 mm, p=0.001), and higher Ki-67 (31.1% vs 15.9%, p<0.001). After a mean follow-up of 8.4 years, TNBC patients with above median levels of s-triglycerides (> 0.98mmol/L) compared to TNBC patients with below median levels of s-triglycerides (≤ 0.98mmol/L) had 3.0 times higher risk for breast cancer recurrence or breast cancer specific death (HR 3.02, 95% CI 1.21-7.55), and 3.4 times higher overall mortality risk (HR 3.41, 95% CI 1.38-8.45). Among the TNBC patients, women with above median s-triglycerides had 15% lower 5-year disease-free survival (76% vs 91%) and 18% lower 5-year overall survival (74% vs 92%) compared to women with below median s-triglycerides. Conclusions: Our results strongly support s-triglycerides as an important biomarker for breast cancer outcomes among triple negative breast cancer patients. Table 1: Multivariable adjusted Hazard Ratios (HRs) for incidence breast cancer recurrence or breast cancer specific death, and incidence overall mortality by pre-diagnostic serum-triglycerides among non-triple negative breast cancer (TNBC) and TNBC patients Non-TNBC, n=488 TNBC, n=87 Recurrence or breast cancer specific death (n=90)Overall mortality (n=104) Recurrence or breast cancer specific death (n=24)Overall mortality (n=33) nHR (95% CI)HR (95% CI)nHR (95% CI)HR (95% CI)s-Triglycerides Median ≤ 0.98 mmol/l2571.001.00431.001.00> 0.98 mmol/l2310.87 (0.56-1.35)1.06 (0.70-1.62)443.02 (1.21-7.55)3.41 (1.38-8.45) Tertiles ≤ 0.82 mmol/l1731.001.00261.001.000.83 – 1.22 mmol/l1660.74 (0.44-1.23)0.81 (0.49-1.36)311.37 (0.38-4.98)0.98 (0.31-3.08)≥ 1.23 mmol/l1490.88 (0.50-1.54)1.17 (0.66-1.96)306.63 (1.64-19.3)3.87 (1.52-12.0)p-trend 0.4950.357 0.0050.007 Multivariate Cox proportional Hazard regression model. Adjusted for BMI and age at attendance (continuous), age at diagnosis (continuous), breast cancer stage at diagnosis (categorical), and current smoking (categorical). Abbreviation: CI, confidence interval; n, number of cases; TNBC, triple negative breast cancer Citation Format: Lofterød T, Mortensen ES, Nalwoga H, Wilsgaard T, Frydenberg H, Risberg T, Eggen AE, McTiernan A, Aziz S, Wist EA, Reitan JB, Akslen LA, Thune I. Serum-triglycerides among triple negative breast cancer patients as a biomarker of poor outcome [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-02.

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