Get special offers, recipes, health news, PLUS our FREE seafood cooking guide!
Got it, thanks! Click here for your FREE seafood cooking guide & recipes e-booklet.
Food, Health, and Eco-news
Breast Cancer Study Questions Omega-3s' Preventive Power but Overlooks Context
07/10/2006 By Craig Weatherby
Differences in women's omega-3/omega-6 intake ratios probably explain mixed results of epidemiological research 
by Craig Weatherby 

To put it mildly, reviewing the inconsistent results of studies examining the impact of dietary fats on breast cancer risk can be a head-spinning experience.


And the findings of the largest study to examine the effects of varying levels of fish consumption—hence, varying intake levels of omega-3 fatty acids—on the risk of breast cancer seem, at first blush, to add to the confusion.


However, while attempting to put the new findings in context, we pored over the many relevant medical publications, and our digging uncovered two important points:

  1. Like most such studies, the latest investigation has a major weakness: the failure of its authors to consider omega-3 intake in relation to omega-6 intake when calculating the ability of fish oil to reduce breast cancer risks.
  2. The handful of studies that have taken this ratio into consideration support the basic research, which indicates, very consistently, that fish and omega-3s should help curb the risk of breast cancer.

First things first: basic research supports a protective role for omega-3s

Over the past three years, we've reported on several research studies designed to determine the effects of various fatty acids on the onset of breast cancer in women or on the growth and "invasiveness" of breast cancer cells in culture or in animals.


These studies fall into three categories:

  • "Mechanistic" studies in isolated breast tissue cells
  • Experimental studies in animals
  • Epidemiological studies in groups of women around the world.

The positive results of most mechanistic and experimental (animal) studies—the kinds of reports referred to as “basic” 
research—indicate that omega-3s can substantially retard the growth of breast cancers, and prompt "suicide" among breast cancer cells (a process called apoptosis).

Key Points

  • A new European study finds no reduction in breast cancer risk related to higher fish (i.e., omega-3) consumption, but fails to consider omega-6 intake.
  • Many epidemiological studies detect a protective effect from fish and omega-3s.
  • Studies that measure the omega-3/omega-6 ratio in women's tissues reinforce the critical part dietary context plays in the strong cancer-protective potential of fish and fish oil.
  • Cell and animal studies support the efficacy of omega-3s almost universally, and underscore the importance of the dietary balance between omega-3 and omega-6 fatty acids, with excessive omega-6 intake being a bad thing.

In contrast, most mechanistic studies indicate that omega-6 fatty acids—which predominate in the most common plant oils (soy, canola, cottonseed, and regular safflower and sunflower)—tend to promote the growth of cancers and their degree of “invasiveness”. (To read about some of the key mechanistic studies, see “More Evidence That Fish Oil Inhibits Breast Cancer.” 


However, the results of the epidemiological (population) studies conducted to date have been mixed. 


As the authors of a 2002 evidence review from Sweden put it, “The omega-3 fatty acids, especially long-chain… [EPA and DHA] contained in ‘fatty' fish, have consistently been shown to retard the growth of breast cancer in vitro [test tube cell studies] and in animal experiments. In contrast, studies of the association between fish consumption and breast cancer risk in human populations have not consistently shown inverse associations [i.e., lower risk at higher fish intake levels].” (Terry P et al 2002).


The new study: Failure of fish to reduce risk ignores role of omega-6 intake

The latest epidemiological study was a branch of a large multinational project called The European Prospective Investigation into Cancer and Nutrition, or “EPIC”. (In a prospective study, people are surveyed over time to reveal any statistical relationships between dietary or lifestyle factors and disease risks.)  


This new branch of the multi-part EPIC investigation (Engeset D 2006) constitutes the largest study to date—but far from the most revealing—designed to examine the relationship between fish consumption and breast cancer risk. The authors recruited 310,671 women between 25 and 70 years of age, who completed dietary questionnaires between 1992 and 1998. The researchers then followed the women's health outcomes for an average of 6.4 years.


The authors found a 13 percent reduction in risk among the women who fell into the highest of five categories of fatty fish consumption—an outcome that was deemed statistically non-significant—and they detected no statistically significant reduction in breast cancer risk among women in the highest category of fish intake.


Unfortunately, the EPIC study's authors made the same omission that's undermined the meaningfulness of most such epidemiological studies: they failed to consider the participants' consumption of omega-3 EFAs in relation to their intake of omega-6 EFAs.


Over-consumption of generally pro-inflammatory omega-6 EFAs and under-consumption of generally anti-inflammatory omega-3 EFAs is the rule in developed, industrialized nations. Researchers recommend consuming two to three as much omega-6 EFAs as omega-3 EFAs, but most of us consume 20 to 40 times more omega-6 EFAs than that.


As we've said, this overabundance of omega-6 EFAs stems from people's excessive intake of common vegetable oils (soy, canola, cottonseed, and regular safflower and sunflower) and packaged, prepared, or restaurant foods, most of which contain these oils.


Earlier studies highlight omega-6 intake as a key factor

The authors of the Swedish review cited above (Terry P et al 2002) had this to say in their review:

“Most of the [pre-2002 epidemiological] studies did not show an association between fish consumption or marine fatty acid intake and the risk of hormone-related cancers [i.e., breast and prostate]. Future epidemiologic studies will probably benefit from the assessment of specific fatty acids in the diet, including [the key marine-source omega-3s, EPA and DHA], and… the [intake] ratio of these [in relation] to [intake of] n-6 [omega-6] fatty acids….”


In other words, the Swedes felt that researchers had been overlooking the critical role that intake levels of plant-derived omega-6 play in determining the amounts of omega-3s from fish (EPA and DHA) or plants (ALA) that get through the metabolic “funnel” through which omega-6 and omega-3 EFAs must pass to have any effect in the body.


When, as with most people in developed countries, a woman's diet is extremely high in omega-6 fatty acids, this overabundance keeps dietary omega-3s from even getting into the metabolic funnel, called the delta-6-desaturase pathway.


Thus, an overabundance of omega-6 EFAs will prevent optimal amounts of dietary omega-3s from being incorporated into cell membranes, where they do their preventive work against cancers.


Fortunately, the impact of varying ratios of omega-3 to omega-6 EFAs was explored in six epidemiological studies from around the world, most of which were published after the Swedes' cogent comment about the need to consider omega-6 intake.


Unlike the EPIC study published earlier this month—and most others like it—the authors of each of these six studies recognized the critical role that metabolic competition between omega-3 and omega-6 fatty acids plays in the promotion of breast and prostate cancers.


In each case, they took this critical factor into account, with positive implications for the potential benefits of omega-3s: a potential that can only be realized among women whose diets are much lower than average in omega-6 EFAs.


Study #1: The Singapore Chinese Health Study

This investigation (Gago-Dominguez M 2003) was a prospective epidemiological study designed to determine the effects of dietary omega-3 and omega-6 fatty acids on breast cancer risk in women.


The Singapore Chinese Health Study ran from 1993 through 1998, and was conducted jointly by researchers from the University of Southern California and the National University of Singapore. The results showed that the women who fell into the three highest quartiles (categories) of omega-3 consumption enjoyed a 26 percent lower risk of developing breast cancer during the study's five year period.


The results also showed that the risk of breast cancer among women with the lowest ratio of omega-3 intake to omega-6 intake was 87 percent higher than average. (See “Omega-3s and Fish Seen to Reduce Breast Cancer Risk”.) 


Study #2: The Japan Collaborative Cohort (JACC) Study

Another prospective investigation—the Japan Collaborative Cohort (JACC) Study—followed 26,291 women aged 40-79 years from 1988 to 1990, and found a statistically significant 44 to 50 percent decrease in breast cancer among the women who consumed the most fish and omega-3 fatty acids, respectively (Wakai K, et al 2005).


In a finding similar to that seen in the Singapore study, the postmenopausal women in the JACC study who reported consuming the most vegetable fat—a marker for omega-6 intake—suffered a two-fold increase in breast cancer risk. And, as in the 2003Singapore study, the key factor was the ratio of omega-3 intake to omega-6 intake.


Study #3: Case-control study from France

Researchers from the Unite de Recherche Associee Universite in ToursFranceexamined the fatty acid composition of adipose tissue from 241 patients with invasive, non-metastatic breast carcinoma and from 88 patients with benign breast disease (Maillard V 2002).


They found that women with the highest levels of omega-3s in their fatty breast tissues enjoyed the lowest risk of cancer and that the women with the highest ratio of omega-3 EFAs to omega-6 EFAs had a much lower risk compared with those with the lowest ratio of omega-3 EFAs to omega-6 EFAs.


As they said, “In conclusion, our data based on fatty acids levels in breast adipose tissue suggest a protective effect of n-3 [omega-3] fatty acids on breast cancer risk and support the hypothesis that the balance between n-3 [omega-3] and n-6 [omega-6] fatty acids plays a role in breast cancer.”


Study #4: University of CaliforniaLos Angeles School of Medicine

A team from UCLA collected adipose (fatty) breast tissue from 73 breast cancer patients and 74 healthy controls (Bagga D 2002).


The women with cancer showed substantially higher tissue levels of omega-6 arachidonic acid, compared with their healthy counterparts. Significantly, the UCLA team also detected a trend in the data that suggested marine omega-3s (EPA and DHA) provided a greater protective effect when women's fatty breast tissues were relatively low in omega-6 arachidonic acid.


As they reported, “We conclude that total n-6 PUFAs [omega-6 EFAs] may be contributing to the high risk of breast cancer in the United States and that LC n-3 PUFAs [omega-3 EFAs], derived from fish oils, may have a protective effect.”


Study #5: European Community Multicenter Study on Breast Cancer

A team from the University of North Carolina at Chapel Hill analyzed data from a large, multi-center European study (Simonsen N 1998), in which researchers from five European countries collected samples of the fatty acid content of adipose tissue from postmenopausal women with breast cancer and from healthy controls.


At first, the UNC team found what most studies show when their authors' fail to take the ratio of omega-3 intake to omega-6 intake into consideration: “Considered in isolation, the level of omega-3 or omega-6 fat in adipose tissue displayed little consistent association with breast cancer across study centers.”


But in four out of the five participating medical centers, the women with the highest ratios of long-chain omega-3s to omega-6s enjoyed a substantially reduced risk of breast cancer.


For example, at the center in MalagaSpain, the women with higher omega-3/omega-6 ratios enjoyed a 67 percent reduction in risk, while the women with the highest omega-6 intake experienced a substantially higher risk of breast cancer.


When all five centers—including the one where no risk reduction was seen—were included in the calculations, women with the highest ratio of omega-3s to omega-6 EFAs showed a 35 percent reduction in risk.


As the UNC team said, “While not definitive, these results provide evidence for the hypothesis that the balance between omega-3 and omega-6 fat may play a role in breast cancer.”


Study #6: Yale University School of Medicine and Yale Cancer Center

Researchers at Yale University combined data from two related case-control studies in Connecticut, giving them information on a total of 565 women diagnosed definitively with breast carcinomas and 554 healthy controls (Goodstine SL 2003).


When they restricted their analysis to pre-menopausal women or to women from one county, the women with the highest omega-3/omega-6 ratio had a 41 percent lower risk of breast cancer, compared with the women with the lowest omega-3/omega-6 ratio.


The Yale team came to this conclusion: “These results are consistent with the hypothesis that a higher (n-3)/(n-6) PUFA [omega-3/omega-6] ratio may reduce the risk of breast cancer, especially in pre-menopausal women.”

*Note: Because of its data limitations, this finding was considered statistically non-significant. While that may seem odd given the large size of the risk reduction, statistically significance is a function of all the statistical factors involved, whose interrelationships can be quite complex. Most researchers would consider an effect of this size meaningful, if, as in the case of omega-3s and cancer, it occurs within a context of evidence that renders a positive outcome highly plausible.


What does this all mean?

The evidence from the existing epidemiological studies is mixed overall, as is often the case when researchers attempt to isolate the effects of single dietary factors on the risk of a disease. After all, the relative risk of developing breast cancer is affected by many genetic, lifestyle, and dietary factors.


However, the few studies that have taken into account women's intake of omega-6 EFAs as well as their consumption of omega-3s from fish and fish oil—as did the authors of the six investigations described above—support the overwhelmingly positive indications from test tube and animal studies, which demonstrate quite clearly that omega-3s tend to discourage breast cancer, and that omega-6 fatty acids tend to promote it.


Since there is virtually no evidence that omega-3s pose a risk, and ample evidence to suggest they are protective—while excessive intake of omega-6 EFAs seem to promote breast cancer—it seems smart to eat more fish and fish oil, fewer packaged, prepared, and restaurant foods, and less vegetable oil. The obvious exceptions to the last rule would be oils low in omega-6 EFAs and high in neutral-to-beneficial oils, such oils from olives, macadamia nuts, avocadoes, or hi-oleic strains of safflower and sunflower seeds.


As regular Vital Choices readers know, breast cancer is only one of many chronic diseases that appear linked to sub-optimal dietary ratios of omega-3s and omega-6s, and the sub-clinical pro-inflammatory state such ratios produce.

Given the widespread occurrence of breast cancer in America today, we hope you'll pass this article on to others who may learn something new from it.



  • Abbadia Z, Vericel E, Mathevet P, Bertin N, Panaye G, Frappart L. Fatty acid composition and CD36 expression in breast adipose tissue of premenopausal and postmenopausal women. Anticancer Res. 1997 Mar-Apr;17(2A):1217-21.
  • Bagga D, Capone S, Wang HJ, Heber D, Lill M, Chap L, Glaspy JA. Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer. J Natl Cancer Inst. 1997 Aug 6;89(15):1123-31.
  • Bakker N, Van't Veer P, Zock PL. Adipose fatty acids and cancers of the breast, prostate and colon: an ecological study. EURAMIC Study Group. Int J Cancer. 1997 Aug 7;72(4):587-91.
  •  Chajes V, Hulten K, Van Kappel AL, Winkvist A, Kaaks R, Hallmans G, Lenner P, Riboli E. Fatty-acid composition in serum phospholipids and risk of breast cancer: an incident case-control study in Sweden. Int J Cancer. 1999 Nov 26;83(5):585-90. 
  •  Engeset D, Alsaker E, Lund E, Welch A, Khaw KT, Clavel-Chapelon F, Thiebaut A, Chajes V, Key TJ, Allen NE, Amiano P, Dorronsoro M, Tjonneland A, Stripp C, Peeters PH, van Gils CH, Chirlaque MD, Nagel G, Linseisen J, Ocke MC, Bueno-de-Mesquita HB, Sacerdote C, Tumino R, Ardanaz E, Sanchez MJ, Panico S, Palli D, Trichopoulou A, Kalapothaki V, Benetou V, Quiros JR, Agudo A, Overvad K, Bjerregaard L, Wirfalt E, Schulz M, Boeing H, Slimani N, Riboli E. Fish consumption and breast cancer risk. The European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer. 2006 Jul 1;119(1):175-82. 
  • Folsom AR, Demissie Z. Fish intake, marine omega-3 fatty acids, and mortality in a cohort of postmenopausal women. Am J Epidemiol. 2004 Nov 15;160(10):1005-10.
  • Gago-Dominguez M, Castelao JE, Sun CL, Van Den Berg D, Koh WP, Lee HP, Yu MC. Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in post-menopausal Chinese women in Singapore. Carcinogenesis. 2004 Nov;25(11):2143-7. Epub 2004 Jul 15.
  •  Gago-Dominguez M, Yuan JM, Sun CL, Lee HP, Yu MC. Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study. Br J Cancer. 2003 Nov 3;89(9):1686-92.
  •  Hermann S, Linseisen J, Chang-Claude J. Nutrition and breast cancer risk by age 50: a population-based case-control study in Germany. Nutr Cancer. 2002;44(1):23-34. 
  •  Holmes MD, Hunter DJ, Colditz GA, Stampfer MJ, Hankinson SE, Speizer FE, Rosner B, Willett WC. Association of dietary intake of fat and fatty acids with risk of breast cancer. JAMA. 1999 Mar 10;281(10):914-20.
  • Jakovljevic J, Touillaud MS, Bondy ML, Singletary SE, Pillow PC, Chang S. Dietary intake of selected fatty acids, cholesterol and carotenoids and estrogen receptor status in premenopausal breast cancer patients. Breast Cancer Res Treat. 2002 Sep;75(1):5-14.
  • Khor GL. Dietary fat quality: a nutritional epidemiologist's view. Asia Pac J Clin Nutr. 2004 Aug;13(Suppl):S22. 
  • Kushi LH, Potter JD, Bostick RM, Drinkard CR, Sellers TA, Gapstur SM, Cerhan JR, Folsom AR. Dietary fat and risk of breast cancer according to hormone receptor status. Cancer Epidemiol Biomarkers Prev. 1995 Jan-Feb;4(1):11-9.
  • London SJ, Sacks FM, Stampfer MJ, Henderson IC, Maclure M, Tomita A, Wood WC, Remine S, Robert NJ, Dmochowski JR, et al. Fatty acid composition of the subcutaneous adipose tissue and risk of proliferative benign breast disease and breast cancer. J Natl Cancer Inst. 1993 May 19;85(10):785-93. 
  • Malmo Diet and Cancer Study: Department of Medicine, Surgery and Orthopedics,Lund UniversitySweden.
  • Rissanen H, Knekt P, Jarvinen R, Salminen I, Hakulinen T. Serum fatty acids and breast cancer incidence. Nutr Cancer. 2003;45(2):168-75.
  • Saadatian-Elahi M, Toniolo P, Ferrari P, Goudable J, Akhmedkhanov A, Zeleniuch-Jacquotte A, Riboli E. Serum fatty acids and risk of breast cancer in a nested case-control study of the New York University Women's Health Study. Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1353-60.
  • Stripp C, Overvad K, Christensen J, Thomsen BL, Olsen A, Moller S, Tjonneland A. Fish intake is positively associated with breast cancer incidence rate. J Nutr. 2003 Nov;133(11):3664-9.
  • Tamakoshi K, Yatsuya H, Wakai K, Suzuki S, Nishio K, Lin Y, Niwa Y, Kondo T, Yamamoto A, Tokudome S, Toyoshima H, Tamakoshi A; JACC Study Group. Impact of menstrual and reproductive factors on breast cancer risk in Japan: results of the JACC study. Cancer Sci. 2005 Jan;96(1):57-62. 
  • Terry P, Rohan TE, Wolk A, Maehle-Schmidt M, Magnusson C. Fish consumption and breast cancer risk. Nutr Cancer. 2002;44(1):1-6. 
  • Thiebaut AC, Chajes V, Clavel-Chapelon F, Gerber M. [Unsaturated fatty acids intake and breast cancer risk: epidemiological data review] Bull Cancer. 2005 Jul;92(7):658-69. Review. French.
  • Vatten LJ, Bjerve KS, Andersen A, Jellum E. Polyunsaturated fatty acids in serum phospholipids and risk of breast cancer: a case-control study from the Janus serum bank in Norway. Eur J Cancer. 1993;29A(4):532-8. 
  • Vatten LJ, Solvoll K, Loken EB. Frequency of meat and fish intake and risk of breast cancer in a prospective study of 14,500 Norwegian women. Int J Cancer. 1990 Jul 15;46(1):12-5. 
  • Velie EM, Schairer C, Flood A, He JP, Khattree R, Schatzkin A. Empirically derived dietary patterns and risk of postmenopausal breast cancer in a large prospective cohort study. Am J Clin Nutr. 2005 Dec;82(6):1308-19. 
  • Welch AA, Lund E, Amiano P, Dorronsoro M, Brustad M, Kumle M, Rodriguez M, Lasheras C, Janzon L, Jansson J, Luben R, Spencer EA, Overvad K, Tjonneland A, Clavel-Chapelon F, Linseisen J, Klipstein-Grobusch K, Benetou V, Zavitsanos X, Tumino R, Galasso R, Bueno-De-Mesquita HB, Ocke MC, Charrondiere UR, Slimani N. Variability of fish consumption within the 10 European countries participating in the European Investigation into Cancer and Nutrition (EPIC) study. Public Health Nutr. 2002 Dec;5(6B):1273-85.
  • Willett WC, Hunter DJ, Stampfer MJ, Colditz G, Manson JE, Spiegelman D, Rosner B, Hennekens CH, Speizer FE. Dietary fat and fiber in relation to risk of breast cancer. An 8-year follow-up. JAMA. 1992 Oct 21;268(15):2037-44.
  •  Wirfalt E, Mattisson I, Gullberg B, Johansson U, Olsson H, Berglund G. Postmenopausal breast cancer is associated with high intakes of omega6 fatty acids (Sweden). Cancer Causes Control. 2002 Dec;13(10):883-93. 
  • Wirfalt E, Vessby B, Mattisson I, Gullberg B, Olsson H, Berglund G. No relations between breast cancer risk and fatty acids of erythrocyte membranes in postmenopausal women of the Malmo Diet Cancer cohort (Sweden). Eur J Clin Nutr. 2004 May;58(5):761-70.
  • Wolk A, Bergstrom R, Hunter D, Willett W, Ljung H, Holmberg L, Bergkvist L, Bruce A, Adami HO. A prospective study of association of monounsaturated fat and other types of fat with risk of breast cancer. Arch Intern Med. 1998 Jan 12;158(1):41-5.
  • Zhu ZR, Agren J, Mannisto S, Pietinen P, Eskelinen M, Syrjanen K, Uusitupa M. Fatty acid composition of breast adipose tissue in breast cancer patients and in patients with benign breast disease. Nutr Cancer. 1995;24(2):151-60.