Randomized placebo-controlled pilot trial of omega 3 fatty acids for prevention of aromatase inhibitor-induced musculoskeletal pain

Abstract

Purpose

Aromatase inhibitor (AI)-induced joint symptoms negatively impact drug adherence and quality of life in breast cancer survivors. Mechanisms underlying symptoms may include inflammation. It is hypothesized that n − 3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and may reduce symptoms.

Methods

We conducted a randomized, double-blind, placebo-controlled study comparing 4.3 g/day n − 3 PUFA supplements vs placebo for 24 weeks in postmenopausal breast cancer patients starting adjuvant AIs. Primary endpoints were adherence and tolerability; secondary outcomes included inflammatory cytokines and symptoms assessed by the Brief Pain Inventory short form (BPI-SF) and Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) at 0, 12, and 24 weeks.

Results

Forty-four women were randomized, of which 35 completed the study. Adherence was ≥ 88% based on these 35 patients with pill counts as well as change in red blood cell (RBC) n − 3 PUFAs. Common toxicities included grade 1 flatulence (55% of both groups) and belching (45% of n − 3 group). Mean pain severity scores (BPI-SF) did not change significantly by time or treatment arm. Quality of life, based on FACT-ES scores, significantly decreased within placebo (p = 0.04), but not the n − 3 group (p = 0.58), with a trend toward between-group differences (p = 0.06) at 12 weeks, but no significant differences at 24 weeks. RBC n − 3 levels were strongly positively correlated with FACT-ES at 12 weeks, but attenuated at 24 weeks.

Conclusion

High-dose n − 3 PUFA supplementation is feasible and well tolerated when administered with AIs. Additional studies are needed to evaluate efficacy in prevention of joint symptoms.

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Acknowledgements

OSU Study #11022; ClinicalTrials.gov Identifier: NCT01478477.

Funding

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under the Award Number UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Correspondence to Maryam B. Lustberg.

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All authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Lustberg, M.B., Orchard, T.S., Reinbolt, R. et al. Randomized placebo-controlled pilot trial of omega 3 fatty acids for prevention of aromatase inhibitor-induced musculoskeletal pain. Breast Cancer Res Treat 167, 709–718 (2018). https://doi.org/10.1007/s10549-017-4559-z

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Keywords

  • Aromatase inhibitors
  • Arthralgias
  • Joint symptoms
  • Omega-3 fatty acids
  • Breast cancer survivors