Antioxidant Vitamins and Breast Cancer

January 2001; Volume 3; 1-5

By Nicola McKeown, PhD

In the united states, breast cancer is second only to lung cancer as the most common cause of cancer mortality in women. In 2000, it is predicted that 182,800 new cases of breast cancer will be diagnosed and that an estimated 40,800 U.S. women will die of this disease.1

The cause of breast cancer is unknown but presumably represents a complex interplay of genetic and environmental factors, including dietary patterns. Migration studies have found that people who migrate from low-risk to high-risk areas acquire the breast cancer rates of the host country within two generations.2 Furthermore, breast cancer rates have been increasing steadily in countries formerly associated with low incidence rates.3,4 Since genetic susceptibility is believed to account for 10-15% of all breast cancer cases,5 non-inherited factors therefore must play a role in breast cancer etiology. Diet has been identified as a potential modifiable risk factor.6

Epidemiological studies have provided evidence that diets rich in fruits and vegetables are associated with decreased risk of breast cancer.7,8 However, few specific dietary factors have been linked definitively to breast cancer predisposition. Some fruits and vegetables are high in antioxidants, such as beta-carotene, vitamin C, and vitamin E. (See Table 1.) It has been hypothesized that these antioxidants protect DNA from damage by scavenging free radicals and inhibiting lipid peroxidation.9 To date, most studies of breast cancer risk and dietary antioxidants have been observational, including both case-control and cohort studies. While case-control studies require fewer people and are less expensive than prospective cohort studies, dietary intake is subject to recall bias among cases; also, the disease may have influenced dietary habits among cases. Prospective cohort studies overcome this limitation by measuring current diet without the presence of the disease; however, individuals need to be followed up for longer periods of time and repeat measures of diet are required to monitor changes in diet.10 This article will review the observational data linking antioxidant intake and breast cancer risk.

Table 1-Typical antioxidant content of selected foods
Antioxidant Food Type Food items Serving Size Nutrient Content of Serving
Beta-carotene Vegetable1 Pumpkin 1/2 cup 17.0 mg
Sweet potato 1 medium 14.3 mg
Spinach 1 cup 9.4 mg
Collards 1 cup, chopped 8.4 mg
Carrots 1/2 cup sliced 6.3 mg
Broccoli 1 medium stalk 1.9 mg
Tomatoes 1 cup, chopped 0.7 mg
Fruit Mangoes 1 medium 0.9 mg
Apricots 1 medium 0.9 mg
Vitamin C Vegetable Broccoli 1 medium stalk 134 mg
(ascorbic acid) Peppers, green, raw 1 cup, sliced 82 mg
Collards 1 cup 35 mg
Tomatoes 1 cup, chopped 34 mg
Cabbage 1 cup 25 mg
Spinach 1 cup 18 mg
Fruit Strawberries 1 cup, sliced 94 mg
Kiwi 1 medium 75 mg
Oranges 1 small 51 mg
Grapefruit 1/2 medium 44 mg
Raspberries 1 cup 31 mg
Vitamin E Vegetable Asparagus 1/2 cup 0.34 mg
(alpha-tocopherol equivalents) Spinach 1 cup 1.7 mg
Broccoli 1 medium stalk 3.0 mg
Collards 1 cup 1.7 mg
Other Sources Wheat germ 1/4 cup 5.1 mg
Sunflower seeds 1/4 cup 18 mg
Vegetable oil2 1 tablespoon 2.9 mg
Margarine, vegetable3 1 tablespoon 1.1 mg
1All vegetables are cooked (boiled and without skin).
2Vegetable oil, canola. 3Margarine-butter blend, 60% corn oil and 40% butter
Adapted from: US Department of Agriculture. USDA Nutrient Database for Standard Reference. Washington, DC: US Dept of Agriculture; 1998. Release 12.


Beta-Carotene Intake

Total vitamin A is comprised of retinol (preformed vitamin A) and some carotenoids (provitamin A) that can be converted to vitamin A in the body. More than 600 naturally occurring carotenoids have been identified; of these, beta-carotene is the best known.11 The effect of reported vitamins A, C, E, and beta-carotene intake on breast cancer risk recently was examined among 83,234 women, aged 30-55, participating in the Nurses’ Health Study.12 After 14 years of follow-up, 2,697 incident cases of invasive breast cancer were identified among women (784 premenopausal and 1,913 postmenopausal) not previously diagnosed with breast cancer. Women with the highest intake of dietary beta-carotene had a lower risk of breast cancer compared to those who ate lower amounts of beta carotene, even after adjustment for age, parity, family history of breast cancer, age at menarche, body mass index, alcohol consumption, or energy intake. This protective association between beta-carotene intake and breast cancer risk also has been observed in case-control studies among women with diagnosed breast cancer.13,14 In both studies, women who consumed approximately > 8.0 mg/d of beta-carotene had a lower risk of dying from their breast cancer than women who had a lower daily beta-carotene intake (< 3.5 mg/d); however, a significant reduction in breast cancer risk was observed in only one study (hazard ratio 0.48; 95% CI 0.23-0.99).14

However, there appear to be inconsistencies among published studies regarding whether there is a relationship between beta-carotene intake and breast cancer risk. Although several case-control and cohort studies on diet and breast cancer support a protective effect of beta-carotene,13,15-19 others have found no association.20-23 Similarly, studies investigating serum/plasma beta-carotene and subsequent risk of breast cancer have not been consistent.20,24,25 Meta-analysis often is used to determine potentially important associations in epidemiological studies that can be missed because of insufficient statistical power.26 A recent meta-analysis of 11 epidemiological studies found that high consumption of beta-carotene (³ 7.0 mg/d) compared to low consumption (£ 1.0 mg/d) was associated with a lower risk (RR = 0.82; 95% CI 0.76-0.91) of breast cancer.8 Inconsistencies in these studies may be in part because of the inherent problems associated with the accurate recording of dietary intake by study participants, the differences in study design, and the different lengths of follow-up in cohort studies. An international panel has concluded that while dietary carotenoids (particularly beta-carotene) may have a weak protective effect against breast cancer risk, uncertainty remained as to whether the protective component was a specific carotenoid or another constituent found in carotenoid-rich foods.7

The Women’s Health Study, a randomized, double-blind, placebo-controlled trial, was designed to examine the health benefits of low-dose aspirin, vitamin E, and beta-carotene on cardiovascular disease and cancer risk among 40,000 female health professionals. The beta-carotene (50 mg on alternative days) component of the trial was terminated after two intervention studies demonstrated that supplementation increased the risk of lung cancer among smokers.27,28 At the time of termination (after a median of 2.1 years), there was no statistical difference in risk of breast cancer between women assigned to beta-carotene and women assigned to placebo.29

Vitamin C

In the United States, several observational studies have examined the association between dietary vitamin C intake and breast cancer risk. In Western New York, a case-control study was conducted among 439 postmenopausal women diagnosed with breast cancer. These women were compared to a random sample of age-matched controls. Researchers found that a daily vitamin C intake (³ 229 mg) was associated with reduced risk of breast cancer.18 Conflicting results have emerged in other case-control studies examining the association between vitamin C intake and breast cancer risk.15,21

In the Nurses’ Health Study, the relationship between vitamin C and breast cancer risk was examined after eight years of follow up in 1,439 women diagnosed with breast cancer, and then again in 2,697 women after 14 years of follow-up.12,30 After adjustment for known and suspected risk factors, vitamin C intake was not associated with decreased breast cancer risk at either follow-up period. This apparent lack of a protective association with high intakes of vitamin C has been confirmed in other prospective studies.23,31,32,33 However, a combined analysis of nine case-control studies found that a high vitamin C intake was associated with a 31% reduction (RR = 0.69;
P < 0.001) in breast cancer risk.34 This association remained after the adjustment for beta-carotene and fiber, two nutrients that independently may decrease breast cancer risk. These data were confirmed in a recent meta-analysis of nine observational studies, which compared a high vitamin C intake (³ 400 mg/d) with low vitamin C intake (£ 50 mg/d) and found that a high vitamin C intake was associated with a reduction (RR = 0.80, 95% CI 0.68-0.95) in breast cancer risk. While there is some evidence to suggest that a high vitamin C intake may decrease breast cancer risk, conclusive evidence is not available.7,21

Vitamin E

The association between vitamin E intake and breast cancer arises primarily from epidemiological studies. Several case control studies have found that high vitamin E intakes were associated with a lower risk of breast cancer.15,17-19,22 However, most cohort studies do not confirm a protective role of vitamin E.12,23,30-32,35 Based on current evidence, it is unlikely that vitamin E plays a considerable role in prevention of breast cancer.7

Dietary Supplements and Breast Cancer Risk

A recent study reported that approximately 81% of women with diagnosed breast cancer reportedly were taking dietary supplements. The most common dietary supplements reported were vitamin E, followed by vitamin C, and multivitamin and mineral supplements.36 However, there is limited information on the effect of dietary supplementation on the recurrence of breast cancer. The majority of observational studies have not found an overall reduced risk of breast cancer among those women who take vitamin C or E supplements.12,18,22,30,32,33 Currently there is no evidence to support the use of vitamin or mineral supplementation in the treatment or prevention of breast cancer.37

Two intervention trials currently are underway to examine whether dietary change or dietary supplements will lead to a decrease in breast cancer risk among U.S. women. The first is the Women’s Health Study. The second study, the Women’s Health Initiative is a large multicenter study involving an observational study and several randomized clinical trials, one of which is a dietary modification intervention. More than 48,000 postmenopausal women between ages 50 and 79 are involved in this intervention that aims to study the effect of a low-fat, high fruit, vegetable, and grain diet on breast cancer risk.38 The planned completion date for this trial is 2007. Both intervention trials will provide important and relevant information on the benefits or risks of supplementation and dietary change in the prevention of breast cancer in women.

Conclusion

Although diets high in fruits and vegetables are associated with lower breast cancer risk, uncertainty remains over which specific dietary constituents are the protective agents. It is unlikely that the observed beneficial effect associated with diets high in fruits and vegetables is due to increased intake of a single nutrient; the interaction of several nutrients is more likely. Women who eat large amounts of fruits and vegetables may have an overall healthier lifestyle and dietary pattern. For example, dietary intakes of fruits, vegetables, and carotenoids reportedly are lower among smokers compared to non-smokers.39,40 Consequently, the health benefits associated with fruit and vegetable intakes may be confounded by other characteristics or unmeasured confounding factors. Diets high in fruits and vegetables have a protective effect against the risk of several diseases, including breast cancer.41 Therefore, from a public health point of view, the current recommendation to increase fruit and vegetable intake should be practiced as part of an overall healthful lifestyle.

Dr. McKeown is a Research Associate at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.

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