Page last updated: Wednesday, November 19, 2008
Facts about the consumption of alcohol and its association with breast cancer
by Creina Stockley of the Australian Wine Research Institute
The editorial of the 15 March 1999 edition of The Medical Journal of Australia, begins by stating that, in Australia, breast cancer causes one death every four hours.The first purported positive association between alcohol consumption and breast cancer was reported by Williams & Horm in 1977, which 50 further epidemiological studies have consistently supported (Longnecker 1994). This association has been observed for both pre and post menopausalwomen,and is irrespective of the type of alcoholic beverage consumed. However, while the association is considered confirmed for consumers of three or more drinks per day, the data is erratic and inconclusive concerning imbibers of one to two drinks a day.

Some studies claim that the relationship between alcohol consumption and breast cancer is linear (Bowlin et al. 1997, Smith-Warner et al. 1998), but this is challenged y by Zhang et al. (1999), who conclude from The Framingham Study, that the light to moderate consumption of alcohol is not associated with an increased risk of breast cancer. It has also been suggested, but not substantiated, that there is a positive relationship between the duration (and hence accumulated amount) of alcohol consumption over the lifespan of a woman and her risk of breast cancer, although age at commencement of alcohol consumption appears to be irrelevant.

The errantry of the data suggests that causation of breast cancer may be multi-factorial. The primary risk factors for breast cancer are purported to be: lifestyle; family history; medical history; nulliparity;endogenous/exogenous hormones (such as hormone replacement therapy); body mass index; and environmental exposure to carcinogens. It has been proposed that alcohol may modify the significance of these risk factors, andin particular, act additively with those risk factors that influence the concentration of hormones in plasma. It has also been proposed that the factors other than family history, may act additively with the family history risk factor, and also, that some of these risk factors may be limited to those women who have a positive family history of breast cancer (Gapstur et al. 1992). Consequently, it has been proposed that the positive association between alcohol and breast cancer may be restricted primarily to women who have a positive family history of breast cancer.

An elevated concentration of testosterone or estradiol increases the risk of breast cancer six- and five-fold, respectively, in both pre and post menopausal women. The concentration of DHEA sulfate, testosterone and estradiol increased across the menstrual cycle following the consumption of alcohol (Muti et al. 1997); and the increase in sulphated DHEA implies that alcohol may also increase the production of DHEA sulfate in the adrenal cortex. Hankinsonet al. (1995) also reported an increase in the plasma concentration of estrone, which is purported to be a primary source of estradiol in breast cancer cells, following the consumption of alcohol. Furthermore, the effect of alcohol on the sex hormones is both acute and chronic.

The data also shows that there is a dose dependent response to alcohol on the aromatization of testosterone and on the subsequent concentration of estradiol in plasma, which then peaked and plateaued (Longnecker et al.1995); this was consistent with the risk of breast cancer in consumers of alcohol compared to abstainers (Longnecker et al. 1988).

The question is the level of moderate consumption at which the elevation of risk occurs, and then relative risk (risk benefit ratio) when compared with other causes of death, such as cardiovascular disease, which increases in post-menopausal women. For example, estrogens significantly lower the concentration of cholesterol in plasma which is positively associated with a decreased risk of mortality from cardiovascular disease.

It has been suggested that the use of ERT per se increases the risk of breast cancer, although the data is inconsistent and hence inconclusive. The suggestion of a further increased risk of breast cancer by post-menopausal woman who use ERT and who are also light to moderate consumers of alcohol remains controversial, in particular as ERT decreases the risk of other diseases such as cardiovascular disease, osteoporosis and potentially Alzheimer’s disease and hence decreases the risk of death from all causes.

Concerning biological or environmental exposure, alcohol is purported to influence the local and systemic metabolism of mammary carcinogens. It is suggested that approximately 50% of breast cancer is not related to genetic/hormonal risk factors, but is related to the environmental risk. With respect to environmental exposure to carcinogens, metabolism in the body may either activate or detoxify the carcinogen. For example:

carcinogen –> toxic intermediates –> detoxified –>excreted??cytochrome P450 enzymesDNA damage –> cancer. Whereby, a decrease in or inhibition of metabolism, increases the exposure of the circulating carcinogen in the blood to organs/tissues, such as the breast.

Because alcohol is not itself genotoxic and nor tumorigenic in animals, potential mechanisms for the positive association between alcohol and breast cancer include the facilitation of carcinogens into cells, the induction of carcinogen activating enzymes, the inhibition of DNA repair and the promotion of tumors. Potential ubiquitous carcinogens include N-Nitrosamines, to which people are exposed from sources such as tobacco.

N-nitrosamine is metabolized bycytochrome P450 enzymes in the liver, such that in the presence of alcohol ,this metabolism is inhibited and the unmetabolized carcinogen circulates in the blood together with the alcohol. The co-exposure of the carcinogen and alcohol to tissues has been observed to promote tumours in these tissues.In addition, cytochrome P450 enzymes have been observed in animal breast tissue and there is greater expression of these enzymes in breast tissue tumours compared to normal breast tissue, such that high concentration of circulating carcinogen may be activated by the cytochrome P450 enzymes and/or alcohol may induce the activation of these enyzmes (Anderson et al.1995). These observations are yet to be confirmed in human breast tissue.

Although animal studies show that alcohol does not initiate or promote tumorogenesis and may actually decrease the incidence of tumours, some studies also show that alcohol may effect or enhance metastasising tumours(Weiss et al. 1995, Swanson et al. 1997), and that this effect is dependent on the stage of alcohol consumption, that is, pre or post treatment with a carcinogen, and on the amount of alcohol consumed. While it is unknown what stage of carcinogenesis is affected by alcohol, recent research implies that alcohol acts at a late stage of carcinogenesis (Weiss et al. 1995,Swanson et al. 1997). Indeed, from human breast cancer cell lines, alcohol is observed to selectively stimulate ER+, but not ER-,estrogen receptors,whereby cancer cells proliferate; this is one suggested aetiology for breast cancer.

Conclusion

While there is an indisputable association between alcohol consumption and the risk of breast cancer. The mechanisms behind the association require further elucidation. This risk of breast cancer should not, however, be considered in isolation from the risk of other factors for mortality, such as cardiovascular disease, whereby cardiovascular disease is the primary cause of mortality in the industrialised or westernised world.Indeed, the light to moderate consumption of alcohol is associated with a significantly reduced risk of mortality from cardiovascular disease and from all causes, for both men and women, irrespective of age and ethnicity (Boffetta and Garfinkel 1990, Marmot and Brunner 1991).

Thus, it may be advisable for women to enumerate and evaluate their risk factors for cardiovascular disease and for breast cancer, in addition to the amount and pattern of their alcohol consumption, before considering abstaining from alcohol.

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