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Milk Products and Breast Cancer

Introduction

The evidence to date indicates that the consumption of milk products is not associated with an increased risk of pre- and post-menopausal breast cancer. Furthermore, emerging evidence indicates that milk product consumption may reduce the risk of breast cancer. While the mechanisms by which milk product consumption may modulate breast cancer risk remain to be elucidated, it appears that some milk components have a key anticarcinogenic effect that may be beneficial in breast cancer. These components are:

• Calcium,
• Vitamin D,
• Lactoferrin.

The Evidence

A 2011 meta-analysis of prospective cohort studies, which included 24,187 cases and 1,063,471 participants, examined the association between the consumption of milk, yogurt, Cottage cheese, butter and other milk products, and breast cancer risk. The following evidence was provided:1

• The summary relative risk of breast cancer for the highest dairy consumption compared with the lowest was 0.85 (95% CI: 0.76-0.95);
• The summary relative risk for milk consumption was 0.91 (95% CI: 0.80-1.02);
• Low-fat milk was statistically significantly associated with reduced breast cancer risk, with a relative risk of 0.93 (95% CI: 0.88-0.99);
• A significant dose-response relationship with breast cancer risk was found for total dairy consumption, but not for milk consumption;
• An increment of 200 g/d of total dairy food was associated with a significant reduction of breast cancer risk, with a relative risk of 0.95 (95% CI: 0.94-0.98).

In a population-based prospective cohort study published in 2010, the relationship between total dairy consumption, the consumption of various milk products, including milk, yogurt, certain types of cheese and ice cream, and pre- and post-menopausal breast cancer risk was investigated among 64,904 Norwegian women.2

• After adjusting for confounding variables such as age, maternal history of breast cancer and mammography practice, total dairy consumption was not associated with risk of pre- or post-menopausal breast cancer;
• The hazard rate ratios for the highest compared with lowest quartile of dairy consumption was 1.07 (95% CI: 0.69-1.65) and 1.07 (95% CI: 0.69-1.65) for pre- and post-menopausal women, respectively;
• Total milk consumption was not associated with either pre- or post-menopausal breast cancer, with hazard risk ratios of 1.23 (95% CI: 0.78-1.94) and 1.03 (95% CI: 0.85-1.25), respectively;
• Milk or dairy consumption in children or adults was also not associated with breast cancer risk;
• Yogurt consumption was not associated with breast cancer, with hazard risk ratios of 0.76 (95% CI: 0.47-1.24) and 0.93 (95% CI: 0.75-1.15) for the highest compared to lowest intake by pre- and post-menopausal women, respectively;
• There was a statistically significant inverse association with the consumption of Norwegian white cheese and pre- and post-menopausal breast cancer;
• Pre-menopausal women who consumed at least 25 g of white cheese per day had a 50% reduced risk compared to those with the least consumption (hazard risk ratios of 0.50, 95% CI: 0.29–0.87), while post-menopausal women had a 20% reduced risk (hazard risk ratios of 0.81, 95% CI: 0.66–0.99).

Another 2010 prospective cohort study of 39,268 pre-menopausal women examined the relationship between diet during adolescence and risk of breast cancer.3

• Total milk intake during adolescence was not associated with risk of breast cancer, with a multivariable-adjusted relative risk of 0.98 (95% CI: 0.71-1.34, ptrend = 0.51) for the highest compared to the lowest quintile;
• Total dairy intake during adolescence was not associated with risk of breast cancer, with a multivariable-adjusted relative risk of 0.90 (95% CI: 0.64-1.27, ptrend = 0.64);
• There was no association with adolescent consumption of full-fat or low-fat milk or milk products and risk of breast cancer.

In a large prospective cohort study conducted among 319,826 European women aged 25 to 70 years, no consistent association was found between milk products, including milk, cheese and butter, and breast cancer risk.4

• The consumption of all types of milk was not associated with risk of breast cancer, with a multivariate hazard ratio of 1.05 (95% CI: 0.97-1.14, ptrend = 0.55) for the highest compared to the lowest quintile;
• High butter consumption was significantly associated with increased breast cancer risk in pre-menopausal women but not in post-menopausal women, with a multivariate hazard ratio of 1.28 (95% CI: 1.06-1.53, ptrend = 0.21).

In a 2009 prospective cohort study with 3,383,377 person-years of follow-up, the following data was provided on cancer risk related to milk product, including milk, yogurt and cheese, as well as calcium intake:5

• After adjustments for confounding variables such as race, family history of cancer, and menopausal hormone therapy use, dairy food consumption was not associated with risk of breast cancer;
• The multivariate relative risk was 0.96 (95% CI: 0.88-1.04, ptrend = 0.28) for the highest compared to the lowest quintile of dairy food consumption;
• Dietary calcium intake was not associated with breast cancer risk, with a multivariate relative risk of 0.94 (95% CI: 0.86-1.03, ptrend = 0.28).

Potential Mechanisms

The mechanisms by which the consumption of milk and milk products such as yogurt, cheese and butter may influence the risk for breast cancer are not clear. Nevertheless, there are key components in milk, namely calcium, vitamin D and lactoferrin, which appear to have important mechanistic anticarcinogenic roles.

A 2010 meta-analysis has shown that there is an inverse relationship between calcium and breast cancer risk. Calcium participates in the regulation of apoptosis, cell proliferation and differentiation. Animal studies have shown that high calcium intake inhibits hyperproliferation of mammary gland induced by high-fat diets and can inhibit mammary carcinogenesis induced by 7,12-dimethylbenz(α)antracene. The anti-proliferation and pro-differentiation properties of calcium may also decrease benign epithelial proliferation disorders.6

Vitamin D has potential mechanistic roles through its anti-cancer and anti-inflammatory properties. Calcitriol, the hormonally active form of vitamin D, exerts anti-proliferative, pro-apoptotic and pro-differentiating effects in many malignant cells.7-9 Vitamin D also opposes estrogen-driven proliferation in mammary glands by reducing progesterone and estradiol levels.8,10

Additionally, studies on mice have demonstrated that supplementation with calcium and vitamin D3 decreases small mammary gland ductules and mitosis, suggesting that these nutrients may regulate normal mammary gland development.11

Bovine milk lactoferrin has also been found to be protective against breast cancer. It appears that lactoferrin has the ability to interact with certain receptors and to modulate the genetic expression of molecules involved in the cell cycle and apoptosis machinery.12

Moreover, data from animal studies indicate that prepubertal exposure to cow’s milk may reduce later susceptibility to mammary tumorigenesis. The protective effect appears to be due to an increase in a protective prepubertal estrogenic environment as well as to a long-term reduction in mammary IGF-1 expression and the number of terminal end buds.13

Another meta-analysis has also indicated that there is no association between animal fat and breast cancer risk. Although some animal and in vitro studies indicate that dietary fat acts as a promoter of carcinogenesis in humans, there is no compelling evidence on mechanisms relating animal fat to increased breast cancer risk. On the other hand, other experimental and in vitro studies have shown that conjugated linoleic acid, which is naturally occurring in milk products, may protect against mammary carcinogenesis.14

Conclusion

Current evidence suggests that the consumption of milk products is not associated with an increased risk of breast cancer and may in fact be associated with a reduced breast cancer risk. More research is needed on the roles of specific milk products such as yogurt, cheese and butter.

Associations may be different for pre- compared to post-menopausal women for certain milk products such as butter. Additional studies are needed for definitive answers.

There is evidence that calcium, vitamin D and lactoferrin are important milk components that have anticancer effects. More studies are needed to elucidate their precise mechanism in the reduction of breast cancer risk.

Furthermore, studies are needed to investigate the role that different fatty acids have on breast cancer risk.

Keywords: breast cancer, lactoferrin, milk, calcium

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