Randomized Multicenter Placebo-Controlled Trial of Omega-3 Fatty Acids for the Control of Aromatase Inhibitor-Induced Musculoskeletal Pain: SWOG S0927.
Musculoskeletal symptoms are the most common adverse effects of aromatase inhibitors (AIs) and can result in decreased quality of life and discontinuation of therapy. Omega-3 fatty acids (O3-FAs) can be effective in decreasing arthralgia resulting from rheumatologic conditions and reducing serum triglycerides.



Women with early-stage breast cancer receiving an AI who had a worst joint pain/stiffness score ≥ 5 of 10 using the Brief Pain Inventory-Short Form (BPI-SF) were randomly assigned to receive either O3-FAs 3.3 g or placebo (soybean/corn oil) daily for 24 weeks. Clinically significant change was defined as ≥ 2-point drop from baseline. Patients also completed quality-of-life (Functional Assessment of Cancer Therapy-Endocrine Symptoms) and additional pain/stiffness assessments at baseline and weeks 6, 12, and 24. Serial fasting blood was collected for lipid analysis.



Among 262 patients registered, 249 were evaluable, with 122 women in the O3-FA arm and 127 in the placebo arm. Compared with baseline, the mean observed BPI-SF score decreased by 1.74 points at 12 weeks and 2.22 points at 24 weeks with O3-FAs and by 1.49 and 1.81 points, respectively, with placebo. In a linear regression adjusting for the baseline score, osteoarthritis, and taxane use, adjusted 12-week BPI-SF scores did not differ by arm (P = .58). Triglyceride levels decreased in patients receiving O3-FA treatment and remained the same for those receiving placebo (P = .01). No between-group differences were seen for HDL, LDL, or C-reactive protein.



We found a substantial (> 50%) and sustained improvement in AI arthralgia for both O3-FAs and placebo but found no meaningful difference between the groups.
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA. dlh23@columbia.edu.
Dawn L
DL
Hershman
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Joseph M
JM
Unger
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Katherine D
KD
Crew
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Danielle
D
Awad
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Shaker R
SR
Dakhil
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Julie
J
Gralow
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Heather
H
Greenlee
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Danika L
DL
Lew
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Lori M
LM
Minasian
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Cathee
C
Till
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
James L
JL
Wade
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Frank L
FL
Meyskens
Dawn L. Hershman, Katherine D. Crew, Danielle Awad, and Heather Greenlee, Columbia University Medical Center, New York, NY; Joseph M. Unger, Danika L. Lew, and Cathee Till, Southwest Oncology Group Statistical Center; Joseph M. Unger, Julie Gralow, Danika L. Lew, Cathee Till, and Carol M. Moinpour, Fred Hutchinson Cancer Research Center, Seattle, WA; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; Lori M. Minasian, National Cancer Institute, Bethesda, MD; James L. Wade III, Central Illinois Community Clinical Oncology Program/Cancer Care Specialists of Central Illinois, Decatur, IL; and Frank L. Meyskens, University of California at Irvine, Chao Family Comprehensive Cancer Center, Orange, CA.
Carol M
CM
Moinpour
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D018771:Arthralgia / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D059352:Musculoskeletal Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009141:Musculoskeletal System / Q000503:physiopathology*; D009367:Neoplasm Staging; D017060:Patient Satisfaction; D017698:Postmenopause; D011788:Quality of Life; D057566:Self Report; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D015525:Fatty Acids, Omega-3