Omega-3 fatty acid use for obese breast cancer patients with aromatase inhibitor-related arthralgia (SWOG S0927)
- 340 Downloads
Although aromatase inhibitors (AIs) prolong survival in post-menopausal breast cancer (BC) patients, AI-associated arthralgia can lead to discontinuation. Obese patients have higher rates of AI arthralgia than non-obese patients, but treatment options are limited. Omega-3 fatty acid (O3-FA) treatment for AI arthralgia has produced mixed results.
We performed an exploratory analysis of SWOG S0927, a multicenter randomized placebo-controlled trial of O3-FA use for AI arthralgia. Post-menopausal women with stage I–III BC taking an AI were randomized to 24 weeks of O3-FAs or placebo. Brief Pain Inventory (BPI) questionnaires and fasting serum were collected at baseline, 12, and 24 weeks. The BPI assessment included worst pain, average pain, and pain interference scores (range 0–10).
Among the 249 participants, 139 had BMI < 30 kg/m2 (56%) and 110 had BMI ≥ 30 kg/m2 (44%). Among obese patients, O3-FA use was associated with significantly lower BPI worst pain scores at 24 weeks compared with placebo (4.36 vs. 5.70, p = 0.02), whereas among non-obese patients, there was no significant difference in scores between treatment arms (5.27 vs. 4.58, p = 0.28; interaction p = 0.05). Similarly, O3-FA use was associated with lower BPI average pain and pain interference scores at 24 weeks compared with placebo among obese patients, but no significant difference between treatment arms in non-obese patients (interaction p = 0.005 and p = 0.01, respectively).
In obese BC patients, O3-FA use was associated with significantly reduced AI arthralgia compared to placebo.
KeywordsBreast cancer Omega-3 fatty acids Aromatase inhibitor Obesity Arthralgia
This study was supported by BCRF, NCI, and SWOG.
This study was funded by the Breast Cancer Research Foundation; National Cancer Institute, Division of Cancer Prevention, NCORP Research Base grant 1UG1CA189974-01.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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.
Informed consent was obtained from all individual participants included in the study.
- 1.Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H et al (2005) Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 366(9484):455–462CrossRefGoogle Scholar
- 2.Coates AS, Keshaviah A, Thurlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M et al (2007) Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1–98. J Clin Oncol 25(5):486–492CrossRefGoogle Scholar
- 3.Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I et al (2007) Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 369(9561):559–570CrossRefGoogle Scholar
- 4.Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS et al (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365(9453):60–62CrossRefGoogle Scholar
- 12.Mieog JS, Morden JP, Bliss JM, Coombes RC, van de Velde CJ, Committee IESS (2012) Carpal tunnel syndrome and musculoskeletal symptoms in postmenopausal women with early breast cancer treated with exemestane or tamoxifen after 2–3 years of tamoxifen: a retrospective analysis of the Intergroup Exemestane Study. Lancet Oncol 13(4):420–432CrossRefGoogle Scholar
- 15.Lustberg MB, Orchard TS, Reinbolt R, Andridge R, Pan X, Belury M, Cole R, Logan A, Layman R, Ramaswamy B et al (2018) Randomized placebo-controlled pilot trial of omega 3 fatty acids for prevention of aromatase inhibitor-induced musculoskeletal pain. Breast Cancer Res Treat 167(3):709–718CrossRefGoogle Scholar
- 16.Hershman DL, Unger JM, Crew KD, Awad D, Dakhil SR, Gralow J, Greenlee H, Lew DL, Minasian LM, Till C et al (2015) Randomized multicenter placebo-controlled trial of omega-3 fatty acids for the control of aromatase inhibitor-induced musculoskeletal pain: SWOG S0927. J Clin Oncol 33(17):1910–1917CrossRefGoogle Scholar
- 17.Du Bois D, Du Bois EF (1916) A formula to estimate the approximate surface area if height and weight be known. Nutrition 1989 5(5):303–311; discussion 312–303Google Scholar
- 22.Crew KD, Capodice JL, Greenlee H, Brafman L, Fuentes D, Awad D, Yann Tsai W, Hershman DL (2010) Randomized, blinded, sham-controlled trial of acupuncture for the management of aromatase inhibitor-associated joint symptoms in women with early-stage breast cancer. J Clin Oncol 28(7):1154–1160CrossRefGoogle Scholar
- 23.Henry NL, Unger JM, Schott AF, Fehrenbacher L, Flynn PJ, Prow DM, Sharer CW, Burton GV, Kuzma CS, Moseley A et al (2018) Randomized, multicenter, placebo-controlled clinical trial of duloxetine versus placebo for aromatase inhibitor-associated arthralgias in early-stage breast cancer: SWOG S1202. J Clin Oncol 36(4):326–332CrossRefGoogle Scholar
- 24.Rastelli AL, Taylor ME, Gao F, Armamento-Villareal R, Jamalabadi-Majidi S, Napoli N, Ellis MJ (2011) Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Res Treat 129(1):107–116CrossRefGoogle Scholar
- 30.Hubalek M, Oberguggenberger A, Beer B, Meraner V, Sztankay M, Oberacher H, Schubert B, Wildt L, Seeber B, Giesinger J et al (2014) Does obesity interfere with anastrozole treatment? Positive association between body mass index and anastrozole plasma levels. Clin Breast Cancer 14(4):291–296CrossRefGoogle Scholar
- 34.Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P et al (2018) Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77917 individuals. JAMA Cardiol 3(3):225–234CrossRefGoogle Scholar