A Randomized Multicenter Phase II Study of Docosahexaenoic Acid in Patients with a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease.

TitleA Randomized Multicenter Phase II Study of Docosahexaenoic Acid in Patients with a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease.
Publication TypeJournal Article
Year of Publication2018
AuthorsGucalp A, Zhou XK, Cook ED, Garber JE, Crew KD, Nangia JR, Bhardwaj P, Giri DD, Elemento O, Verma A, Wang H, J Lee J, Vornik LA, Mays C, Weber D, Sepeda V, O'Kane H, Krasne M, Williams S, Morris PG, Heckman-Stoddard BM, Dunn BK, Hudis CA, Brown PH, Dannenberg AJ
JournalCancer Prev Res (Phila)
Volume11
Issue4
Pagination203-214
Date Published2018 04
ISSN1940-6215
KeywordsBiomarkers, Tumor, Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Docosahexaenoic Acids, Double-Blind Method, Female, Fibrocystic Breast Disease, Follow-Up Studies, Gene Expression Profiling, Humans, Middle Aged, Neoplasm Invasiveness, Precancerous Conditions, Prognosis
Abstract

Obesity, a cause of subclinical inflammation, is a risk factor for the development of postmenopausal breast cancer and is associated with poorer cancer outcomes. Docosahexaenoic acid (DHA), an omega-3 fatty acid, possesses anti-inflammatory properties. We hypothesized that treatment with DHA would reduce the expression of proinflammatory genes and aromatase, the rate-limiting enzyme for estrogen biosynthesis, in benign breast tissue of overweight/obese women. A randomized, placebo-controlled, double-blind phase II study of DHA given for 12 weeks to overweight/obese women with a history of stage I-III breast cancer, DCIS/LCIS, Paget's disease, or proliferative benign breast disease was carried out. In this placebo controlled trial, the primary objective was to determine whether DHA (1,000 mg by mouth twice daily) reduced breast tissue levels of TNFα. Secondary objectives included evaluation of the effect of DHA on breast tissue levels of COX-2, IL1β, aromatase, white adipose tissue inflammation, and gene expression by RNA-seq. Red blood cell fatty acid levels were measured to assess compliance. From July 2013 to November 2015, 64 participants were randomized and treated on trial (32 women per arm). Increased levels of omega-3 fatty acids in red blood cells were detected following treatment with DHA ( < 0.001) but not placebo. Treatment with DHA did not alter levels of TNFα ( = 0.71), or other biomarkers including the transcriptome in breast samples. Treatment with DHA was overall well-tolerated. Although compliance was confirmed, we did not observe changes in the levels of prespecified biomarkers in the breast after treatment with DHA when compared with placebo. .

DOI10.1158/1940-6207.CAPR-17-0354
Alternate JournalCancer Prev Res (Phila)
PubMed ID29453232
PubMed Central IDPMC6290902
Grant ListHHSN261201200034C / CP / NCI NIH HHS / United States
N01CN35159 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States