Critique 128: Little effect of alcohol consumption on breast cancer risk found among African-American women — 14 November 2013

Chandran U, Zirpoli G, Ciupak G, McCann SE, Gong Z, Pawlish K, Lin Y, Demissie K, Ambrosone CB, Bandera EV.  Does alcohol increase breast cancer risk in African-American women?  Findings from a case–control study.  British J Cancer 2013;109:1945–1953 | doi: 10.1038/bjc.2013.513.

Authors’ Abstract

Background:  Alcohol is an important risk factor for breast cancer in Caucasian women, but the evidence in African-American (AA) women is limited and results are inconclusive.

Methods:  Associations between recent and lifetime drinking and breast cancer risk were evaluated in a large sample of AA women from a case–control study in New York and New Jersey.  Multivariable logistic regression models provided odds ratios (ORs) and 95% confidence intervals (CIs).

Results:  There was no association between recent drinking and breast cancer risk, even when stratified by menopausal status or by hormone receptor status.  A borderline decreased risk with increased lifetime consumption was found (OR = 0.77; 95% CI: 0.58–1.03), which was stronger among women who drank when under 20 years of age (OR = 0.65; 95% CI: 0.47–0.89), regardless of menopausal or hormone receptor status.

Conclusion:  Breast cancer risk associated with recent alcohol consumption was not apparent in AA women, while early age drinking seemed to decrease risk.  This is the first investigation on recent and lifetime drinking in subgroups and drinking during different age periods in AA women. If findings are replicated, racial differences in biological pathways involving alcohol and its metabolites should be explored.

Forum Comments

Background:  There are very limited data relating alcohol consumption to the risk of breast cancer among African-American (AA) women.  In 2000, a report by Kinney et al found little evidence for an increased risk of breast cancer among AA women who consumed alcohol, either currently or throughout their lifetime [Kinney AY, Millikan RC, Lin YH, Moorman PG, Newman B.  Alcohol consumption and breast cancer among black and white women in North Carolina (United States).  Cancer Causes Control 2000;11:345-357].  However, the number of AA women in that study was not large.

In a review in 2012, Chandran et al found two prospective cohorts and three case-control studies that gave breast cancer risk estimates for alcohol consumption in AA women.  Evidence was mixed on the relation in AA women, and most confidence intervals included 1.0.  These authors concluded that the impact of alcohol in AA women is currently inconclusive, given the few studies, with relatively small samples, and limited range of alcohol intake (Chandran U, Hirshfield KM, Bandera EV.  The role of anthropometric and nutritional factors on breast cancer risk in African-American women.  Public Health Nutr 2012;15:738-748; doi: 10.1017/S136898001100303X) .

The present study is based on a total of 803 cases of breast cancer among AA women included in a case-control study in New Jersey and New York.  The authors found no significant associations between recent or previous drinking and breast cancer risk, even when stratified by menopausal status or by hormone receptor status. 

Comments on the present study:  Reviewer Ellison points out a number of limitations of this study: “(1) it is a case-control study of breast cancer, which always presents an opportunity for recall bias; (2) the number of cases is not large (n=803), but it is among the largest available datasets on AA women; (3) AA women generally drink very little, so it may be difficult to determine if larger amounts of alcohol might increase breast cancer risk.

“On the other hand, there are a number of strengths of the study, including the following: (1) it is based on a very well-done and complete analysis, with appropriate control for known risk factors; (2) similar results were obtained when recent (in last year) alcohol intake and long-term alcohol consumption were considered; (3) their finding of increased risk of breast cancer among subjects with a family history of breast cancer, a personal history of benign breast disease, and HRT use strengthen the results; (4) the authors carried out appropriate sensitivity analyses; (5) results were consistent after stratification by menopausal status and hormone receptor status of tumors; and, especially, (6) the results of this study are consistent with those from many  previous studies showing little effect of alcohol consumption on breast cancer risk among AA women.”

Forum member Thelle added: “I am not quite sure in which direction the recall bias should go in this case.  I guess the hypothesis that alcohol may be associated with breast cancer is well known among both cases and controls.  Also, a selection bias because of low participation from eligible controls is another source of concern.  The number of participants, and especially drinkers in the higher consumption categories, is small, so misclassifications in both directions may have occurred here.”

Reviewer Waterhouse was not sure how to assess this study, but thought that perhaps the small number of subjects here and the very low consumption rate would have made it impossible to detect a small increase in risk that might be present.  “In other words, the variation in their data is too large to be able to detect the anticipated risk increase of about 5% among all drinkers, in that there were many non-drinkers, the drinkers averaged only small amounts of alcohol, and there were very small numbers of high-alcohol consumers.”

Reviewers Finkel and de Gaetano emphasized that cancer risk may be related to long-term alcohol consumption.  “All cancers, not breast cancer specifically, take years to develop, so the last 12 months’ exposure to a possibly risk-altering factor is not important.  Such data are irrelevant to the question of whether cancer is associated with drinking.”  On the other hand, the authors found similar results when the reported recall of drinking practices earlier in life were considered.

Reviewer Van Velden wrote: “I am not sure if the authors of this paper determined the folic acid intake on their FFQ.  Alcohol seems to have negative effects only in woman with folate deficiency.  Genetic markers for breast cancer should be taken into consideration as well.” 

Forum reviewers thought that the decrease in breast cancer risk by early drinking (<20 years of age) reported in this study may well be due to uncontrolled confounding by SES or other variables.  We would assume that the AA women who drank alcohol early in life may have been those from more highly educated, more prosperous black families, so higher SES may have been a residual confounder despite adjustments in the analysis.

Are there ethnic differences in the association between alcohol and breast cancer?  Overall, Forum members are not sure that the present study indicates that there may be genetic differences between whites and blacks affecting the relation of alcohol to breast cancer; instead, the risk reported in whites is rather small to begin with, and the whites who consumed alcohol in this study did not demonstrate an increase in breast cancer risk either.   Nevertheless, this study adds important information on alcohol and breast cancer risk. 

Forum member Skovenborg agreed with other reviewers, stating “There is no convincing evidence of a difference in alcohol metabolism between white men and women and African-American men and women.  The study of alcohol consumption and risk of breast cancer has always been a study of weak associations, and a null finding in the present cohort of African-American women – indeed a very light drinking cohort with a median intake of alcohol of 16 grams per week – is no surprise.  Even in Caucasian women in this study, associations between recent drinking, lifetime consumption and breast cancer risk were mostly null.”  Added Reviewer de Gaetano: “Lack of association based on an 800 subject case-control study is not surprising and cannot be taken as an absence of association.  This study, though well performed except for the sample size, does not generate any new idea or hypothesis.”

Reviewer Goldfinger stated: “The comment that there is no convincing evidence of a difference in alcohol metabolism between white men and women and African-American men and women questions what was expected from this investigation.  AAs appear to have different consumption habits and drinking patterns.  This paper did not have the power to detect differences in such patterns or among wine, beer, or spirits consumers.  These would have been interesting variables to focus on.”

Forum Summary

Alcohol is known to be a risk factor for breast cancer in Caucasian women, but the evidence in African-American (AA) women is limited and results from previous studies are inconclusive.  The present case-control study, based on 803 cases of breast cancer among African American women in the northeastern part of the USA, evaluated associations between recent and lifetime drinking and breast cancer risk.  The authors report that there was no association between recent drinking and breast cancer risk, even when stratified by menopausal status or by hormone receptor status.  Further, their analyses suggested a slight decrease in cancer risk with alcohol consumption among women who drank when under 20 years of age (OR = 0.65; 95% CI: 0.47–0.89), regardless of menopausal or hormone receptor status.

Forum reviewers point out that this was a case-control study of breast cancer, which always presents an opportunity for recall bias, and the number of cases was not large.  Further, AA women generally drink very little, so it may be difficult to determine if larger amounts of alcohol may increase breast cancer risk. 

On the other hand, the results were based on a very well-done and complete analysis, with appropriate control for known risk factors, similar results were obtained when recent (in last year) alcohol intake and long-term alcohol consumption were considered, and their finding of increased risk of breast cancer among subjects with a family history of breast cancer, a personal history of benign breast disease, and HRT use strengthen the results. 

The results of this study are consistent with those from many previous studies showing little effect of alcohol consumption on breast cancer risk among AA women.  However, given that few AA women in the USA drink alcohol, and those that do typically consume only small amounts, the study cannot estimate the potential effect on breast cancer among heavier drinkers.  Further, Forum members believed that the decrease in the risk of breast cancer found in this study for drinking early in life (before age 20 years) may be due to residual confounding by socio-economic factors.

Overall, the present study supports previous research suggesting that the light alcohol consumption typically seen among AA women in the USA is not an important factor in their risk of breast cancer.  On the other hand, this paper reports similar null results between alcohol and cancer risk among Caucasian women in their study.  Current data do not necessarily indicate that there are ethnic differences in alcohol metabolism that may lead to differences between Caucasian and AA women in the association of alcohol consumption with breast cancer, and this study alone cannot be used to support such a premise.

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Comments on this paper were provided by the following members of the International Scientific Forum on Alcohol Research:

R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA

Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark

Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis; Davis, CA, USA

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA

David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway

Giovanni de Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy

Creina Stockley, PhD, MBA, Clinical Pharmacology, Health and Regulatory Information Manager, Australian Wine Research Institute, Glen Osmond, South Australia, Australia

Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, Dept. of Cardiology, University of Arizona School of Medicine, Tucson, Arizona, USA

Dag S. Thelle, MD, PhD, Senior Professor of Cardiovascular Epidemiology and Prevention, University of Gothenburg, Sweden; Senior Professor of Quantitative Medicine at the University of Oslo, Norway