Researchers from the Zhejijang University in China investigated the association between the consumption of fish and marine n-3 PUFAs and the risk of breast cancer and a potential dose-response association.
The systematic review involved 21 independent prospective cohort studies that included over 20,000 cases of breast cancer and involved over 800,000 participants from across the United States, Europe and Asia, with an average follow-up time ranging from 4.3 to 20 years.
Researchers investigated the association between fish consumption, marine n-3 PUFAs and alpha linolenic acid (ALA)- a plant based n-3 PUFA, and the risk of breast cancer. Seventeen articles from 16 independent cohort studies, involving 16,178 breast cancer events and 527,392 participants, looking at the association of marine n-3 PUFAs and breast cancer risk, were included in the review.
Intake of marine n-3 PUFAs from fish was associated with a 14% reduction of risk of breast cancer, and this result remained similar whether omega-3 was measured as dietary intake or as tissue biomarkers.
Researchers also found with a dose-response analysis that the risk of breast cancer was reduced by 5% per 0.1 g/day or 0.1% energy/day of marine-derived omega-3 fatty acids. However, they didn’t find any significant association between the risk of breast cancer and fish consumption or ALA.
“Dietary intake of marine n-3 PUFA, but not ALA, was associated with a lower risk of breast cancer. Fish consumption was not associated with risk,” the authors wrote.
“Our present study provides solid and robust evidence that marine n-3 PUFAs are inversely associated with risk of breast cancer. The protective effect of fish or individual n-3 PUFA warrants further investigation of prospective studies.”
Fish oil supplements reduce breast cancer in the VITAL cohort
In 2010, researchers found an association between a reduced risk of breast cancer and the use of supplemental fish oil in the VITamins And Lifestyle (VITAL) cohort, a study of men and women designed to investigate prospectively the association of vitamin, mineral, and specialty supplements with cancer risk.
The researchers investigated the use of fish oil supplements in 35,016 postmenopausal women aged 50 to 76 years during the 10-year period before baseline. They concluded that fish oil supplementation was associated with a reduced risk of breast cancer and is a potential candidate for further chemoprevention studies with an emphasis on timing, dose and therapeutic action.
The role of omega-3 in breast cancer outcomes
While the BMJ study found no association between fish consumption and the risk of breast cancer, a 2010 study reported an association with a reduced risk of additional breast cancer events and all-cause mortality in women who had been diagnosed and treated for early stage breast cancer. 
Published in the Journal of Nutrition, researchers investigated whether there was an association between dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), n-3 PUFAs found in fish, and additional breast cancer events and all-cause mortality, and whether there was a difference in outcomes based on the source of EPA and DHA- either from food or from supplements.
In this cohort study involving 3081 women, researchers found that a higher intake of EPA and DHA from food was associated with a 25% reduction in the risk of additional breast cancer events and a dose-dependent reduced risk of all-cause mortality.
While the study authors found no association between breast cancer outcomes and EPA and DHA obtained from fish oil supplements, they did note that the use of supplements among the participants was low (<5%). It may also indicate that other nutrients found in fish, in addition to EPA and DHA, play a role in decreasing subsequent breast cancer events and all-cause mortality in breast cancer survivors.
The role of omega-3 in breast cancer risk reduction
The role of n-3 PUFAs, in particular EPA and DHA in reducing the risk of breast cancer and improving patient outcomes, is thought to be due in part to their anti-inflammatory properties. They partially replace pro-inflammatory arachidonic acid (AA) in cell membranes and by utilising cyclo-oxygenase and lipoxygenase at AAs expense leading to a reduced production of inflammatory chemicals including PGE2.[2,4,5]
Research in the past decade has identified metabolic products of EPA and DHA which have direct effects in resolution of inflammation (resolvins) and tissue protection (protectins) including protection in the central nervous system (neuroprotectins) at picomolar levels which may play a major role in cancer prevention, given the contribution of inflammation and mitotic stimulation to the development and progression in many cancers. [REFS]
An additional chemoprotective action may be due to inhibition of eicosanoid production, regulation on transcription factor activity, gene expression and signal transduction of cell growth. Omega-3 from fish oils may also affect oestrogen metabolism by decreasing oestrogen production and oestrogen cell growth, important in oestrogen dependent cancers such as breast cancer. [1,5]
- Dietary changes in the past century have led to a marked reduction of omega-3 fats relative to omega-6 fats in the western diet. The first focus of clinicians should be advice on increasing dietary long-chain omega-3 fats from foods such as fish.
- Females convert plant-based omega-3 fats such as ALA to long-chain EPA and DHA with a higher efficiency than males, meaning that sufficient ALA may contribute to risk reduction in females but only at relatively high intake (in the order of 20 grams or more of flaxseed oil). This may prove practically difficult to achieve, and it is the likely reason that no effect was seen in the trial above.
- Where dietary intake of omega-3 fatty acids is insufficient, the available evidence and Australian dietary guidelines would support the use of long-chain omega-3 supplementation not only for breast cancer risk reduction, but for cardiovascular, mental health and inflammation control benefits in the dosage range of 1000 to 3000 mg per day of the EPA + DHA. This translates to between 3 and 10 of the standard 1 gram fish oil capsules per day, or lower numbers of the newer, more concentrated EPA + DHA supplements.
- Zheng J et al. Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. BMJ 2013;346:f3706 doi: 10.1136/bmj.f3706 (Published 27 June 2013)
- Brasky T.M, Lampe J.W, Potter J.D, Patterson R.E, White E. Speciality Supplements and Breast Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort. Cancer Epidemiol Biomarkers Prev; 2010;19:1696-1708
- Pattersoc R.E et al. Marine fatty acid intake is associated with breast cancer prognosis. J Nutr,2010;201-206
- ALFANO CM, Imayama I, Neuhouser ML, Kiecolt-Glaser JK, Smith AW, Meeske K, McTiernan A, Bernstein L, Baumgartner KB, Ulrich CM, and Ballard-Barbash R. Fatigue, inflammation, and omega-3 and omega-6 fatty acid intake among breast cancer survivors. J Clin Oncol. 2012;30:1280-1287.
- Braun L, Cohen M. Herbs & Natural Supplements: an evidence-based guide 3rdedition Chatswood Elsevier, 2010:426-444