Critique 078: An update on the association of alcohol consumption with risk of breast cancer ———— 10 April 2012
Seitz HK, Pelucchi C, Bagnardi V, La Vecchia C. Epidemiology and Pathophysiology of Alcohol and Breast Cancer: Update 2012. Alcohol and Alcoholism 2012; doi: 10.1093/alcalc/ags011
Aims: To update epidemiological data on alcohol and breast cancer, with special emphasis on light alcohol consumption, and to review mechanisms of alcohol mediated mammary carcinogenesis.
Methods: For epidemiological data, in November 2011 we performed a literature search in various bibliographic databases, and we conducted a meta-analysis of data on light alcohol drinking. Relevant mechanistic studies were also reviewed to November 2011.
Results: A significant increase of the order of 4% in the risk of breast cancer is already present at intakes of up to one alcoholic drink/day. Heavy alcohol consumption, defined as three or more drinks/day, is associated with an increased risk by 40–50%. This translates into up to 5% of breast cancers attributable to alcohol in northern Europe and North America for a total of approximately 50,000 alcohol-attributable cases of breast cancer worldwide. Up to 1–2% of breast cancers in Europe and North America are attributable to light drinking alone, given its larger prevalence in most female populations when compared with heavy drinking. Alcohol increases estrogen levels, and estrogen may exert its carcinogenic effect on breast tissue either via the ER or directly. Other mechanisms may include acetaldehyde, oxidative stress, epigenetic changes due to a disturbed methyl transfer and decreased retinoic acid concentrations associated with an altered cell cycle.
Conclusions: Women should not exceed one drink/day, and women at elevated risk for breast cancer should avoid alcohol or consume alcohol occasionally only.
Background: Most observational epidemiologic studies have shown that consumers of alcohol tend to have an increased risk of developing breast cancer. A clear threshold of effect has not been shown consistently, but many studies show a slight increase in risk even among women who state that they average only one drink/day.
The percentage increase in risk associated with light drinking is rather small, generally ranging between 4 and 10%. And, it has been pointed out that even with such an increase in breast cancer risk, the net effects on total mortality of women consuming these amounts are favorable because of the greater decrease in risk of cardiovascular diseases associated with moderate amounts of alcohol.
The present paper provides an update on epidemiologic data relating alcohol with risk of breast cancer, with a focus on “light-moderate” consumption (up to an average of one drink/day). It also discusses the pathophysiology involved, and provides recommendations for women as to alcohol consumption.
Specific comments on the paper: Forum reviewers found this to be an excellent review and meta-analysis, providing a good update on the relation of alcohol consumption to the risk of breast cancer in women. It is important that the authors presented results specifically for light drinkers (up to 1 drink/day), a pattern of drinking very common in many parts of the world.
Their results indicate that even for light drinkers, there is a significant increase in risk of breast cancer, shown in both cohort studies and case-control studies. The increase in risk is approximately 4% for women who consume no more than one drink/day. Given the high prevalence of light drinking (rather than heavier drinking) among women in Europe and North America, the authors estimate that such light drinking is attributable for 1 to 2% of breast cancers occurring in these regions.
There were a number of concerns about the paper expressed by Forum reviewers:
(1) The meta-analysis of alcohol and breast cancer goes into great detail, but does not discuss potential reasons for the substantial heterogeneity among studies (which was more common among case-control studies).
(2) There is no discussion of the influence of folate intake on the association between alcohol and breast cancer. Many studies suggest that women with high folate levels show little or no effect of alcohol on the risk of breast cancer.1
(3) There is no discussion of “the alcoholism paradox,” i.e., the much lower risk of breast cancer among alcoholic women that would be expected from the projection of risk estimates from the general population.2
(4) While the authors conclude that extra precautions should be taken regarding alcohol for women at high risk of breast cancer, they do not mention that studies have shown that alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation.3
A reviewer concluded that the authors could have better emphasized that pre-menopausal women have a relatively low cardiovascular risk, and get therefore a lower potential benefit from moderate alcohol; thus the risk of breast cancer should be taken into account when one is discussing alcohol consumption with such women. On the contrary, post-menopausal women have approximately four times greater risk of cardiovascular disease than of breast cancer. Thus, strictly from a health point of view, moderately drinking women may wish to pay more attention to the potential benefits of alcohol in markedly lowering cardiovascular and less to the real, but slight, increase in the risk of breast cancer.
1. Tjønneland A, et al. Folate intake, alcohol and risk of breast cancer among postmenopausal women in Denmark. Eur J Clin Nutr 2006;60:280-286.
2. Kuper H, et al. Alcohol and breast cancer risk: the alcoholism paradox. British Journal of Cancer 2000;83:949–951.
3. Dennis J, et al. Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers. The Breast 2010;19:479-483.
An excellent review paper on the relation of alcohol consumption to the risk of breast cancer concludes that, overall, there is a positive dose-response relation between alcohol drinking and the risk of breast cancer. The analysis shows that an increase in risk is seen even among women reporting an average of only about one drink/day. Given the high prevalence of such light drinking in most female populations, the authors estimate that up to 1 to 2% of breast cancers in Europe and North America may be attributable to light drinking alone. Thus, while alcohol appears to be a risk factor for breast cancer, it does not explain a very high percentage of cases.
Forum members considered this to be a well-done analysis, with a good review not only of epidemiologic studies but of potential mechanisms of effect of alcohol on breast cancer risk. An increase in estrogen levels from alcohol seems to be the physiologic mechanism most commonly suggested for the increase in risk.
The meta-analysis is noteworthy in presenting risks specifically for women who consume up to one drink/day, which is the common pattern for a high proportion of women in western cultures. On the other hand, the authors failed to discuss the potential modification of alcohol effects on cancer risk from folate in the diet; in many studies, high folate levels tend to diminish or eliminate an increase in risk from alcohol. Further, the paper does not provide a discussion of the net effects of moderate drinking on mortality. In older women, the decrease in the risk of cardiovascular disease (a much more common cause of death than breast cancer) greatly exceeds the potential increase in risk of death from breast cancer.
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Contributions to this critique were provided by the following members of the International Scientific Forum on Alcohol Research:
Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway
Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA
Giovanni de Gaetano, MD, PhD, Research Laboratories, Catholic University, Campobasso, Italy
Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark
R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA