Life Extension Magazine October 2008
New Scientific Options for Preventing Breast Cancer
Research Update on Compounds to Incorporate Into Your Breast Health Program
By Laurie Barclay, MD
One of the most frightening events that a woman will ever face is being diagnosed with breast cancer. While many women diligently seek health screenings to catch this insidious disease in its early stages, few of us realize the cancer-preventive potential of nutrients such as vitamin D and pomegranate.
These scientifically documented agents provide powerful protection against breast cancer through a number of fascinating mechanisms. By favorably affecting gene expression, pomegranate, green tea, curcumin, and vitamin D can restore healthy cell division patterns,1-4 while soy extracts can help guard against estrogen’s hyper-proliferating effects.5
One in eight women in the United States will be diagnosed with this life-threatening disease during her lifetime.6 Even with all the advances in pharmaceutical technology, mortality rates for breast cancer have remained stagnant for the past few decades. As the scientific evidence for natural cancer-protective compounds continues to mount, many of today’s leading scientists believe that a multi-pronged nutritional strategy holds the key in helping to win the war against breast cancer.
The Epidemic of Breast Cancer
Today, breast cancer is the most frequently diagnosed cancer in American women, excluding skin cancer.7 This is in part due to earlier and more frequent detection with mammography and breast examination, but also due to increasing risk factors for breast cancer. These risk factors include delayed childbearing, having fewer children, use of pharmaceutical hormone replacement therapy, and obesity, especially in postmenopausal women.8 In the United States, an estimated 178,480 new cases of invasive breast cancer were diagnosed in 2007, along with more than 40,000 deaths, making breast cancer the second leading cause of cancer death in women.7
Natural Options for Preventing Breast Cancer
Recent studies offer hope that vitamin D and foods-beverages such as green tea, pomegranate, curcumin, and soy may help promote breast health and reduce breast cancer risk. These foods are rich in healthful compounds known as polyphenols, which are active in many pathways that regulate cell growth and metabolism.
“Research has indicated these compounds have a potential not only in prevention of breast cancer but also for treatment,” Bharat B. Aggarwal, PhD, Ransom Horne, Jr., professor of cancer research at the University of Texas M.D. Anderson Cancer Center in Houston, tells Life Extension magazine. “Most of the natural products, including vitamin D, green tea, pomegranate, and curcumin, mediate their effects through modulation of multiple cell signaling targets.”
“This is a big advantage because scientists are beginning to realize that multi-targeted therapies are needed for the treatment of cancer,” says Dr. Aggarwal, who is also a professor of cancer medicine in biochemistry, and chief of the cytokine research laboratory, Department of Experimental Therapeutics, at M.D. Anderson. “These natural products are designed to be multi-targeted naturally.”
Cancer-Preventive Potential of Vitamin D
Vitamin D, created by the body in response to sunlight, and present in fortified milk, fish, and fish liver oils has long been touted as a natural preventive agent against bone loss seen with aging and the menopause. But can it also benefit breast health?
“Vitamin D seems to reduce cell division in many types of cells,” Julia Knight, PhD, associate professor of public health sciences at the University of Toronto, Ontario, Canada, tells Life Extension. “Too much cell division can lead to cancer development.” Dr. Knight, who is also a senior investigator and leader at the Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto, notes further, “Vitamin D is also important for other reasons such as for bone health.”
Marilyn Tseng, PhD, an associate member of the Fox Chase Cancer Center, in Philadelphia, PA, agrees that numerous lines of evidence suggest that vitamin D might be protective against cancer. These include population studies showing lower breast cancer rates in areas of the US that get more sunlight, and laboratory studies showing that vitamin D has anticancer effects.9
In addition, epidemiological studies show that women with low vitamin D intake tend to have high breast density on mammograms, which is associated with increased risk for breast cancer.10,11 Lower amounts of sun exposure are also linked to increased breast cancer risk in light-skinned women.12
“The active form of vitamin D in the body (1,25-dihydroxyvitamin D) is thought to have several anticarcinogenic (anticancer) effects, including inhibition of cell proliferation and induction of apoptosis (natural cell death), Dr. Tseng tells Life Extension.
Laboratory studies have shown that 1,25-dihydroxy-vitamin D suppresses growth of breast cancer by blocking signals that stimulate cancer cell growth, by enhancing signals that inhibit cancer cell growth, and by favorably altering regulators of the cell cycle.1 This three-pronged attack can prevent mutated cells from becoming malignant and even induce cancer cell death. In addition, vitamin D plays a role in the effects hormones have on breast cancer, including the potential stimulating effects of growth hormone and prolactin.13,14
Vitamin D may also help prevent or modulate breast cancer through interactions with the vitamin D receptor in mammary cells. By binding with the vitamin D receptor in healthy cells, 1,25-dihydroxyvitamin D influences proteins involved in cell differentiation, survival, and proliferation. The active form of vitamin D may discourage proliferation and promote differentiation in breast cancer cells that are vitamin D receptor-positive.15
In one investigation, scientists prospectively examined the relationship of vitamin D and calcium intake to breast cancer incidence. Higher intake of vitamin D and calcium was associated with a modestly reduced risk of breast cancer in premenopausal women. Interestingly, the protective benefits were more pronounced for more aggressive breast tumors.16
Another large prospective study examining the relationship between vitamin D intake and breast cancer risk in postmenopausal women found that those who consumed at least 800 IU per day from diet and supplemental sources had a lower risk than those consuming less than 400 IU daily. Vitamin D’s protective effect was most pronounced during the first five years after the baseline dietary assessment and against estrogen- and progesterone-receptor negative cancers.17
A recent case-control study comparing 1,394 postmenopausal breast cancer patients with 1,365 controls showed that low levels of 25-hydroxyvitamin D (the primary circulating form of vitamin D and precursor to 1,25-dihydroxyvitamin D) were significantly related to breast cancer risk. In fact, women in the highest category of 25-hydroxyvitamin D blood level had an amazing 70% reduction in their risk of breast cancer. This association was even stronger in women who never used menopausal hormone therapy.18
A pooled analysis examining the dose-response association between serum vitamin D levels and breast cancer risk revealed that women with serum 25-hydroxyvitamin D levels of approximately 52 ng/mL (130 nmol/L) had a 50% lower risk compared with women who had serum levels <13 ng/mL (32 nmol/L). This protective serum level correlates with approximately 4,000 IU of vitamin D daily.19
According to Dr. Knight, the optimal amount of vitamin D supplementation may vary based on an individual’s amount of sun exposure,12 intake from dietary sources such as fortified milk and fatty fish, and use of supplements. Fortified milk, as well as some brands of soy milk, contain about 100 IU per cup on average.
For people living in northern latitudes, vitamin D supplementation is more important in the winter, when little vitamin D is obtained from the sun.20 People with darker skin need more sun exposure than do lighter-skinned people to make the same amount of vitamin D, and as a result, they often have lower blood levels of vitamin D.
“Supplements of 800 and 1,000 IU vitamin D can now be obtained and are sometimes recommended to older women, along with calcium, to prevent osteoporosis,” Dr. Knight says. “The optimal amount to prevent breast cancer is unknown and may vary by age and other factors.” Dr. Knight believes that additional research would be helpful to evaluate the optimal blood levels of vitamin D for different aspects of health and the effect of individual factors such as age, skin color, body weight, geographic location, and sun exposure on the optimal amount for supplementation.
Other experts have proposed that daily intake of 1,000-4,000 IU vitamin D is needed to obtain healthy serum levels of 25-hydroxyvitamin D of 30 ng/mL (75 nmol/L), which may confer protection against breast cancer and other malignancies such as colon, prostate, ovarian, lung, and pancreatic cancers.9
Excessive vitamin D intake can result in hypercalcemia, or increased blood calcium levels. The potentially harmful effects of hypercalcemia may include gastrointestinal symptoms, depression, confusion, and more frequent urination in greater amounts. While the Institute of Medicine’s established upper limit of vitamin D is 2,000 IU per day, recent clinical trials in healthy adults have found no evidence of toxicity at doses ≥10,000 IU/day.21
Protecting Against Breast Cancer with Green Tea
“Green tea, traditionally used in Chinese medicine, has several health benefits including antioxidant, anti-inflammatory and anticancer effects,” Arpita Basu, PhD, assistant professor of nutritional sciences at Oklahoma State University in Stillwater, tells Life Extension. “Keeping in view the high burden of breast cancer among US women, and the increasing use of complementary and alternative medicine, green tea phytochemicals deserve special attention in breast cancer prevention and treatment.”
Green tea is rich in plant compounds known as polyphenols that can help prevent disease. The most active group of green tea polyphenols are the catechins, particularly epigallocatechin gallate (EGCG).
Laboratory data from cell culture and animal models provide convincing evidence for the anticancer effects of green tea polyphenols, or of EGCG, on breast cancer.2,22-24 In laboratory studies, green tea polyphenols and EGCG have been shown to suppress the growth and reproduction of human breast cancer cells.25,26 Of even greater interest, these beneficial compounds in green tea delay the appearance of tumors in mouse models of breast cancer27 and cut down on the total tumor burden (amount of cancer in the body) when human breast cancer cells are injected into laboratory mice.26
“In mouse models of breast cancer, green tea catechins induced cell death, leading to smaller tumors and longer survival, and also caused a reduction in the tumor oxidative products,” Dr. Basu says. “Thus, the anticancer effects of green tea extend beyond its antioxidative and anti-inflammatory properties, which also independently contribute to decreased risks of breast cancer.”
Other exciting benefits of green tea include inhibition of vascular endothelial growth factor (VEGF) production,27,28 which cuts off the blood supply needed for tumor growth; down-regulation of estrogen receptor-alpha function in breast cancer cells;29 reduction of tumor invasiveness;27 and increased apoptosis, or programmed cell death, in cancer cells.30
“Oxidative stress has been implicated in promoting growth and malignancy of cancers including breast cancer,” Jian-Wei Gu, MD, assistant professor of physiology and biophysics at the University of Mississippi Medical Center in Jackson, tells Life Extension. “Aside from the role of free radicals in the induction of mutation, oxidative stress also alters cell signaling pathways involved with apoptosis [programmed cell death] resistance, proliferation [growth], angiogenesis [new blood vessel formation], and metastasis [spread]. Therefore, antioxidants, especially EGCG in green tea, can inhibit tumor progression.”
A fascinating experiment by Dr. Gu’s laboratory showed that EGCG, 50-100 mg/kg/day, added to the drinking water of female mice inhibited growth of breast cancer. After five weeks of EGCG treatment, the weight of breast tumors shrunk an astounding 68% in mice consuming EGCG daily, and the tumors were 66% smaller.31
This effect appeared to result from EGCG blocking the growth of blood vessels to the tumors, thereby choking off their blood supply.31
The anticancer effects of green tea have been shown to work together with and enhance those of the natural supplement curcumin;32 of reishi mushroom (used in traditional Chinese medicine);33 of the breast cancer drug tamoxifen;34 and even of the monoclonal antibody trastuzumab, which is used alone or in combination with chemotherapy for breast cancer.35
“Some observational studies have suggested a significantly decreased risk of breast cancer as well as improvement of clinical features of breast cancer malignancy associated with green tea consumption,” Dr. Basu says, citing two reports.36,37 “However, these studies do not suggest a cause and effect relationship but provide a basis for green tea catechin interventions in clinical trials.”
Studies in healthy human volunteers have shown that consuming green tea catechins is safe and may enhance the body’s ability to detoxify carcinogens that increase cancer risk.38 In an ongoing trial, the National Cancer Institute is testing the effect of green tea polyphenols in 288 patients with breast cancer.39 Dr. Basu is enthusiastic that the results of this trial “will conclusively prove the anticancer effects of green tea phytochemicals.” A phase II study examining green tea’s chemoprevention effects against breast cancer is also under way.40
Based on the evidence to date, Dr. Basu notes that drinking two to four cups of freshly brewed green tea a day should be considered one of many healthy dietary choices in preventing primary or recurring breast cancers, and that supplements may also be appropriate.
Another expert weighing in on the question of green tea and breast health is Min Zhang, PhD, MD, a senior research fellow in the School of Population Health at the University of Western Australia.
A case-control study in Southeast China by Dr. Zhang’s group showed that regularly drinking green tea is associated with decreased risk for breast cancer.41
“Our research showed that regular consumption of green tea can protect against breast cancer,” Dr. Zhang tells Life Extension. “The accumulated evidence from other studies suggested that green tea supplements may have similar benefits as drinking green tea.”
To examine this further, Dr. Zhang’s group is planning a clinical study in breast cancer patients, comparing the effects of encapsulated green tea extract with those of placebo.