Breast cancer is the second most common cancer among women, with more than 200,000 women diagnosed each year.
Exposing breast tissues to higher levels of estrogen over a long period of time can increase a woman's risk of developing the disease … especially the “estrogen dependent” forms.
The drug tamoxifen – which is a synthetic version of a compound from yew trees – reduces estrogen's ability to exert estrogenic effects in breast cells, which can be cancer-promoting in a substantial proportion of women.
Now, researchers at Fox Chase Cancer Center report that omega-3 fatty acids – which are essential to human life and are found only in seafood – could be a safe and beneficial booster for tamoxifen therapy.
Mixed estrogen message from the Women's Health Initiative
We should note today's report of a new analysis of data from the Women's Health Initiative (WHI) estrogen-alone clinical trial.
Launched in 1993, it randomly assigned more than 10,739 women between the ages of 50 and 79—all of whom were past menopause and had had a hysterectomy—to take daily estrogen or a placebo.
The new WHI data analysis showed that in this group, estrogen-only treatment was associated with a significantly lower risk of breast cancer, regardless of age and had little to no effect on the risk of death, coronary heart disease, colorectal cancer, and hip fractures, or on other serious health problems (NCIB 2011).
However, while estrogen-only therapy reduced the risk of heart disease and death among women in their 50s, it markedly increased those risks for women in their 70s.
In 2004, the study was stopped early because of an increased risk of stroke and blood clots in women receiving estrogen. But nearly 80 percent of the participants agreed to keep being monitored; this most recent analysis covers nearly 11 years of follow-up.
This report follows cell, animal, and clinical studies that found omega-3s boosting the efficacy of tamoxifen and certain chemo or radiation therapies on breast and colon cancers … while reducing drug side effects (Benais-Pont G et al. 2006; Manni A et al. 2009; Calviello G et al. 2009; Kikawa KD et al. 2009; Manda K et al. 2010).
Tamoxifen and raloxifene are both associated with increased risk of blood clots, so anything that allows dose reductions is desirable. Coincidentally, omega-3s also possess significant anti-clotting powers.
A primer on Tamoxifen
Tamoxifen has been used for more than 30 years to treat breast cancer in women and men.
According to the National Cancer Institute, the benefits of tamoxifen as a selective preventer of, and treatment for, breast cancer are firmly established and far outweigh the potential risks (NCI 2011).
Tamoxifen is used to treat early-stage and metastatic breast cancer. It also helps prevent new cancers in the other breast and prevents successfully treated breast cancer from returning.
The results of the Breast Cancer Prevention Trial (BCPT) showed a reduction in diagnoses of invasive breast cancer among women who took tamoxifen for five years
The results of the STAR clinical trial found tamoxifen and raloxifene (Evista) equally effective for reducing the risk of invasive breast cancer in postmenopausal women at increased risk of the disease.
In 2010, researchers reported that tamoxifen prevented more cases of breast cancer than raloxifene … a 50 percent drop in risk over a seven-year period, compared with 38 percent for raloxifene (American Association for Cancer Research AACR 101st Annual Meeting).
Let's look at the new study's details and major findings.
Mouse study tests fish oil + tamoxifen, echoes positive results of prior research
The new findings were presented at the 102nd Annual Meeting of the American Association for Cancer Research (AACR) by Jose Russo, M.D., director of the Breast Cancer Research Laboratory at Philadelphia's Fox Chase Cancer Center.
Wake Forest review sees encouraging evidence
A research-literature review published three years back by scientists from North Carolina's Wake Forest University offered a balanced overview of the evidence (Berquin IM et al. 2008):
Fox Chase is a National Cancer Institute Comprehensive Cancer Center and its researchers have won two Nobel Prizes. The study was supported by a grant from Susan G. Komen for the Cure.
The Fox Chase team conducted the study in collaboration with a team led by Andrea Manni, M.D., from Pennsylvania State University, who first reported their similar tamoxifen + omega-3s mouse study two years ago (Manni A et al 2009 and 2010).
For the new study, the Russo/Manni team induced mammary tumors in rats and then divided the animals into four groups.
They fed the groups either a 17 percent fish oil diet, with or without tamoxifen, or a 20 percent corn oil diet, with or without tamoxifen, for eight weeks.
We could not access the as yet unpublished study to see whether these were percents of calories or ounces.
Either way, 17 percent is an enormous proportion of any animals' diet. The researchers probably wanted a very large omega-3 intake to increase the chance that any benefit or harm would be detectable within the two-month period of the trial. (Sacrificing accuracy, perhaps.)
They then analyzed gene “expression” patterns in the tumors, because genes control pretty much everything that cells do or don't do.
The mice given a diet high in fish oil showed greater expression of genes related to cellular “differentiation” (specialization) – a sign of lower cancer severity – compared with a diet high in corn oil.
The combination of fish oil and tamoxifen also reduced the expression of genes linked to tumor growth and spreading.
“If a tumor was being treated with tamoxifen, the addition of an omega-3 fatty acid diet seemed to make the tumor, at least at the molecular level, more benign and less aggressive and responsive to tamoxifen,” says Russo. (FCCC 2011)
The fish oil diet also boosted the expression of genes related to immune defenses against tumors, more so than did the corn oil diet.
Undesirable gene effects are likely outweighed by beneficial ones
Oddly, the omega-3 group showed increased expression of genes that trigger inflammation and allergic reactions … effects that could curtail the ability of cells to fight cancer and could promote the spread of tumor cells.
This was unexpected, because omega-3s almost always tend to moderate inflammation and allergic responses.
It is conceivable that the negative gene expressions resulted from the extremely large amounts the mice were eating … a whopping 17 percent of their calories.
However, the positive indications seen in this and prior studies suggest that any hypothetically undesirable effects of omega-3s in rodents with cancer are outweighed by fish fats' positive influences on cancer control.
As Russo said, more studies are needed to fully understand the effects of fish oil on animal and human immune systems as it relates to cancer.
For more on prior research – including a similar mouse study that combined omega-3s and tamoxifen – see “Cancer Findings Bolster Omega-3s' Breast and Prostate Potential”
Meanwhile, Dr. Russo's team is examining whether omega-3 fish fats can prevent breast cancer in animals, and testing the influence of diet on breast cancer risk in women.
Benais-Pont G, Dupertuis YM, Kossovsky MP, Nouet P, Allal AS, Buchegger F, Pichard C. Omega-3 polyunsaturated fatty acids and ionizing radiation: combined cytotoxicity on human colorectal adenocarcinoma cells. Nutrition. 2006 Sep;22(9):931-9. Epub 2006 Jun 30.
Berquin IM, Edwards IJ, Chen YQ. Multi-targeted therapy of cancer by omega-3 fatty acids. Cancer Lett. 2008 Oct 8;269(2):363-77. Epub 2008 May 13. Review.
Calviello G, Serini S, Piccioni E, Pessina G. Antineoplastic effects of n-3 polyunsaturated fatty acids in combination with drugs and radiotherapy: preventive and therapeutic strategies. Nutr Cancer. 2009;61(3):287-301. Review.
Fox Chase Cancer Center (FCCC). Fox Chase researchers find that fish oil boosts responses to breast cancer drug tamoxifen.April 6, 2011. Accessed at http://www.eurekalert.org/pub_releases/2011-04/fccc-fcr032711.php
Gillet L, Roger S, Bougnoux P, Le Guennec JY, Besson P. Beneficial effects of omega-3 long-chain fatty acids in breast cancer and cardiovascular diseases: voltage-gated sodium channels as a common feature? Biochimie. 2011 Jan;93(1):4-6. Epub 2010 Feb 16. Review.
Kikawa KD, Herrick JS, Tateo RE, Mouradian M, Tay JS, Pardini RS. Induced oxidative stress and cell death in the A549 lung adenocarcinoma cell line by ionizing radiation is enhanced by supplementation with docosahexaenoic acid. Nutr Cancer. 2010;62(8):1017-24.
Kim J, Lim SY, Shin A, Sung MK, Ro J, Kang HS, Lee KS, Kim SW, Lee ES. Fatty fish and fish omega-3 fatty acid intakes decrease the breast cancer risk: a case-control study. BMC Cancer. 2009 Jun 30;9:216.
Manda K, Kriesen S, Hildebrandt G, Fietkau R, Klautke G. Omega-3 fatty acid supplementation in cancer therapy : does eicosapentanoic acid influence the radiosensitivity of tumor cells? Strahlenther Onkol. 2011 Feb;187(2):127-34. Epub 2011 Jan 18.
Manni A et al. Combination of fish oil and Tamoxifen is superior to Tamoxifen alone for breast cancer prevention. In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 April 18-22; Denver, CO.
Manni A, Xu H, Washington S, Aliaga C, Cooper T, Richie JP Jr, Bruggeman R, Prokopczyk B, Calcagnotto A, Trushin N, Mauger D, Verderame MF, El-Bayoumy K. The impact of fish oil on the chemopreventive efficacy of tamoxifen against development of N-methyl-N-nitrosourea-induced rat mammary carcinogenesis. Cancer Prev Res (Phila). 2010 Mar;3(3):322-30. Epub 2010 Feb 23
Minami Y, Miyata H, Doki Y, Yano M, Yamasaki M, Takiguchi S, Fujiwara Y, Yasuda T, Monden M. [omega-3 Fatty acid-containing diet (Racol) reduces toxicity of chemoradiation therapy for patients with esophageal cancer]. Gan To Kagaku Ryoho. 2008 Mar;35(3):437-40. Japanese.
NCI Cancer Bulletin (NCIB). Menopausal Estrogen Therapy Benefits and Risks Vary by Age, WHI Analysis Suggests. April 5, 2011; Volume 8 / Number 7. Accessed at http://www.cancer.gov/ncicancerbulletin/040511/page4
National Cancer Institute (NCI). Tamoxifen: Questions and Answers. Accessed at http://www.cancer.gov/cancertopics/factsheet/Therapy/tamoxifen
Wendel M, Heller AR. Anticancer actions of omega-3 fatty acids--current state and future perspectives. Anticancer Agents Med Chem. 2009 May;9(4):457-70. Review.