Abstract P1-09-30: Relationship of dietary and red blood cell polyunsaturated fatty acids to inflammatory markers in breast cancer survivors taking aromatase inhibitors

Introduction: A large body of literature supports modulation of inflammation by polyunsaturated fatty acids (PUFA). Inflammation may play a role in the painful joint symptoms commonly experienced by breast cancer survivors taking aromatase inhibitors (AI). AI-induced joint symptoms negatively impact drug adherence and quality of life in many breast cancer survivors. N-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory effects; in contrast, excess very long chain n-6 PUFAs may promote peripheral and joint inflammation. We hypothesized that breast cancer survivors with greater EPA+DHA or n-3/n-6 PUFA in their diet would have decreased inflammation and be less likely to develop AI-induced joint symptoms. Materials and methods: This is a secondary analysis of PUFA intake self-reported from food frequency questionnaires and red blood cell (RBC) PUFA data from a randomized placebo-controlled pilot study comparing n-3 PUFA supplementation vs placebo in 44 postmenopausal women with breast cancer initiating first line adjuvant AIs. Primary outcomes were feasibility and tolerability; secondary outcomes were differences in clinical symptoms and inflammatory markers. Participants were randomized to 4.8 g/day DHA+EPA vs matched placebo for 24 weeks (wks). Serial peripheral blood samples were drawn for RBC PUFA levels and inflammatory cytokines (IL-6, TNFα-R2 and IL-17). Clinical symptoms were assessed by the Brief Pain Inventory short form (BPI-SF), FACTB-ES, and Stanford Health Assessment -Disability Index (HAS) at 12 and 24 wks. Compliance and toxicity were evaluated monthly. Results: Median age of all 44 women enrolled and randomized was 60 years (range 43-76); breast cancer stage I (n=29), II (n=10), III (n=5); prior taxane (n=15, 34%).Baseline mean dietary intakes of n-3 PUFAs were: total n-3 PUFAs = 1.43 ± 0.86 g/d; EPA = 0.05 ± 0.05g/d; and DHA = 0.10 ± 0.11 g/d. There was a trend toward lower TNFα-R2 with higher dietary intake of EPA (p=0.09) and DHA (p=0.10). Baseline mean RBC EPA+DHA (n-3 Index) was 4.36% and the RBC n-3/n-6 ratio was 0.20. RBC total n-3 PUFAs were similar at baseline between n-3 treatment and placebo groups (6.6 ± 1.6%, 7.2 ±1.9%, p=0.20). RBC PUFAs were not predictive of baseline IL-6 or IL-17. However, the baseline RBC n-3 Index trended toward an inverse relationship with TNFα-R2 (r = -0.23, p 0.14) Mean dietary intake of n-3 PUFAs did not change over 24 wks for the 30 women with complete FFQ data and blood samples: total n-3 = 1.38 ± 0.70 g/d; EPA = 0.06 ± 0.07 g/d; and DHA = 0.13 ± 0.14 g/d. Dietary EPA and DHA were significantly associated with lower TNFα-R2 (r = -0.40, p=0.02 for both) at 24 wks. RBC total n-3 PUFAs were significantly higher in the n-3 treatment vs placebo group at wk 24 (6.5%±1.0% vs 15.0%±3.3%, p Conclusions: There was a trend toward lower TNFα-R2 in breast cancer survivors with higher dietary and RBC EPA and DHA before starting AIs, but only dietary intake of EPA and DHA was significantly related to lower TNFα-R2 after 24 wks of AI therapy. Citation Format: Tonya S Orchard, Xueliang Pan, Joanne Lester, Amanda Logan, Charles L Shapiro, Rebecca D Jackson, Martha A Belury, Lisa Yee, Maryam B Lustberg. Relationship of dietary and red blood cell polyunsaturated fatty acids to inflammatory markers in breast cancer survivors taking aromatase inhibitors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-30.