Abstract

The ratio of omega-3 to omega-6 fatty acids, especially the long-chain eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) to arachidonic acid (AA) ratio, is inversely associated with breast cancer risk. We measured the association between cytologic atypia, a biomarker for short-term risk of breast cancer development, and omega-3 and omega-6 fatty acid intake and levels in blood and breast tissue. Blood and benign breast tissue, sampled by random periareolar fine-needle aspiration (RPFNA), was obtained from 70 women at elevated risk for breast cancer. Self-reported dietary intake was assessed by the NCI's Food Frequency Questionnaire. The fatty acid composition of five lipid compartments, red blood cell, plasma and breast phospholipids, and plasma and breast triaclyglycerides (TAG), was analyzed by gas chromatography as weight percent. Median daily intakes of EPA+DHA and total omega-3 fatty acids were 80 mg and 1.1 g, respectively. The median total omega-3:6 intake ratio was 1:10. Compared with women without atypia, those with cytologic atypia had lower total omega-3 fatty acids in red blood cell and plasma phospholipids and lower omega-3:6 ratios in plasma TAGs and breast TAGs (P < 0.05). The EPA+DHA:AA ratio in plasma TAGs was also lower among women with atypia. This is the first report of associations between tissue levels of omega-3 and omega-6 fatty acids and a reversible tissue biomarker of breast cancer risk. RPFNA cytomorphology could serve as a surrogate endpoint for breast cancer prevention trials of omega-3 fatty acid supplementation.

Highlights

  • Omega-3 and omega-6 fatty acids are essential nutrients, because they cannot be made endogenously

  • Women were eligible for random periareolar fine-needle aspiration (RPFNA) on the basis of any of the following: (i) an affected close relative under the age of 60; (ii) a prior breast biopsy revealing atypical hyperplasia, lobular carcinoma in situ, DCIS, or prior invasive breast cancer; (iii) multiple breast biopsies; (iv) atypia found on a previous

  • Seventy (n 1⁄4 70) agreed to complete the diet history questionnaire (DHQ-I) and to have additional fasting blood obtained for fatty acid analysis

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Summary

Introduction

Omega-3 and omega-6 fatty acids are essential nutrients, because they cannot be made endogenously. Humans lack enzymes to convert omega-6 fatty acids to omega-3 fatty acids and vice versa. The dietary ratio translates into differences in blood and breast tissue [1]. The majority of omega-3 and omega-6 fatty acids consumed are the 18-carbon essential fatty acids, alpha-linolenic acid (ALA), and linoleic acid (LA). ALA and LA share elongases and desaturases that convert them into longchain (20- and 22-carbon) fatty acids (see Fig. 1). Arachidonic acid (AA), the predominant long-chain omega-6 fatty acid, is a key component of plasma membrane phospholipids (PL), from where it can be released and converted into potent proinflammatory eicosanoids by cyclooxygenase (COX) and lipoxygenase (LOX) enzymes [5, 6].

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