Address by Howard D. Maccabee, Ph.D, M.D., to The Society of Medical Friends of Wine at their Quarterly Dinner Meeting at the Mark Hopkins Hotel , San Francisco, June 17, 1998

As physicians and  friends of wine, we may sometimes get into uncomfortable situations when asked to give advice to women about alcohol and breast cancer, specifically with respect to wine. In general, we know from personal experience and  from scientific data that moderate wine consumption is healthful, that it can improve the quality of life, and may even increase longevity. The most convincing recent evidence for this was published in the New  EnglandJournal of Medicine on December 11, 1997. Dr. Michael Thun, Richard Peto, and their colleagues from the American Cancer Society and the Epidemiology Unit at Oxford showed that women who have one drink daily have a lower death rate than women who consume no alcohol. The greatest benefit seems to be from reduction of deaths from all cardiovascular diseases. The benefit is statistically significant and is substantial,  with a 21% reduction in deaths per year.

With respect to breast cancer, however, recently published evidence is not so favorable. In February of this year, Dr. Stephanie Smith-Warner from Harvard and colleagues from the United States and Europe concluded that alcohol consumption is associated with a linear increase in breast cancer incidence in women, over a wide range of consumption. This was published in JAMA and was  a pooled analysis of prospective cohort studies, which are felt to be more reliable than prior case-control studies. They calculated a 9% increase in breast cancer risk for each 10 gm serving of alcohol  daily.

Before this year, there had been multiple publications on the subject, with mixed conclusions. Freudenheim and her colleagues reviewed New York State health records and concluded that "there was little evidence of increased risk of breast cancer with intake of alcohol," except for a "weak indication of an increase in risk with beer for intakes of at least one drink per day." In fact, they found a lifetime risk of only 80% compared to nondrinkers, for a subgroup of women who averaged at least one drink of wine daily. Longnecker and his colleagues, however, concluded that alcohol consumption was clearly related to breast cancer risk, as published in the Journal of the NCI in 1995. For 10 gm of alcohol daily, they also calculated a 9% increase in risk, but this increased even faster than linear extrapolation.

Jean-Francois  Viel and French colleagues did a case-control study of premenopausal women and found a statistically significant increase in those who consumed four liters or more of red wine per month (i.e., more than 16 gm per day). Curiously, however, they found a statistically significant reduction in risk for women who did consume alcohol, but less than 12 gm per day.

There are several more published studies, but I will only quote  one more: a Canadian case-control study by Rosenberg et al., published in 1990, which calculated a multivariant risk reduction of 1% for women who drank at least one alcoholic beverage per day. It is interesting to note  that they also found an increased risk for women who drank beer and a decreased risk for women who drank wine, but neither estimate was statistically significant.

What is the mechanism by which alcohol could affect breast cancer risk? Alcohol appears to increase circulating levels of estrogenic hormones in postmenopausal women. This has been shown in two recent studies. Hankinson and her colleagues at Harvard showed that alcohol consumption was positively associated with estrone sulfate concentration in plasma, and Ginsburg and her Massachusetts colleagues showed that alcohol ingestion increased circulating estradiol in women on  estrogen replacement therapy. Strangely though, alcohol did not change estradiol in women not on estrogen replacement. It is interesting that Hankinson also found increased plasma estrogen in obese postmenopausal  women, and postmenopausal obesity is, along with low physical activity, one of the few reversible "environmental" factors that are well-accepted risk factors for breast cancer (reference Morgan et al., American Council for Science and Health, 1997).

Well, what should the conscientious health professional make of all this? Clearly, there are mechanisms by which alcohol consumption can affect estrogen levels in  postmenopausal women, and estrogen affects the breast. The natural estrogen levels in premenopausal women, however, would be large enough to overwhelm these limited effects of alcohol. The data on younger women are also less statistically reliable because of the lower cancer incidence in younger women.

Furthermore, some of the prospective studies that were pooled to give the influential linear risk estimate were themselves not linear. For example, the Iowa Women's Health Study showed no increased risk until consumption was more than 15 gm daily. The New York Cohort Study did not show increased risk below 30 gm daily. But, of course, this is a kind of subset analysis which can lead to biased conclusions even more readily than meta-analysis or pooling of data.

Similarly, there is some evidence that not all alcoholic beverages are equal, in the sense of breast cancer risk. At least two studies indicate that beer drinking is associated with higher risk and wine drinking with lower risk than equivalent other-alcohol consumption.

The more important comparison is with respect to overall health. Breast cancer, while it is the most feared disease in women, causes many fewer deaths than cardiovascular disease. If we accept that one glass of wine daily may decrease the overall death  rate by 20%, but may increase the breast cancer death rate by 9%, the overall benefit/risk ratio would be more than 50, because breast cancer causes only about 1 out of 3 women's deaths in the United States.

My conclusion therefore is that it is appropriate to advise women that one drink daily is safe and healthful, especially if it is wine. It may increase the risk of breast cancer slightly, but the overall benefits are  expected to be far greater than the risks.

Bibliography

Freudenheim, J. L. et al., "Lifetime Alcohol Consumption and Risk of Breast Cancer," Nutr. Cancer, 1995; vol. 23, pp.  1-11.

Ginsburg, E. S. et al., "Effects of Alcohol Ingestion on Estrogen in Postmenopausal Women." JAMA, 1996; vol. 276, pp. 1747-1751.

Hankinson, S. E. et al., "Alcohol, Height, and Adiposity in  Relation to Estrogen Levels in Postmenopausal Women." JNCI, 1995; vol. 87, 1297-1302.

Longnecker, N. P. et al., "Risk of Breast Cancer, in Relation to Lifetime Alcohol Cnsumption." JNCI, 1995; vol. 87, pp. 923-292.

Morgan, J. W. et al., "Position Paper of American Council for Science and Health on Risk Factors for Breast Cancer." In press, ACSH, 1997.

Rosenberg, L et al., "Case-Control Study of  Alcoholic Beverage Consumption and Breast Cancer." Am. J. Epidem., 1990; vol. 131, pp. 6-14.

Smith-Warner, S. et al., "Alcohol and Breast Cancer in Women-A Pooled Analysis of Cohort Studies." JAMA, 1998; vol. 279, pp. 535-540.

Thun, M. J. et al., "Alcohol Consumption and Mortality among Middle-Aged and Elderly U.S. Adults." NEJM, 1997; vol. 337, pp. 1705-1714.

Viel, J. F. et al., "Alcoholic Calories, Red Wine Consumption, and Breast Cancer among Premenopausal Women." Eur. J. Epidem., 1997; vol. 13, pp. 639-643.

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"Wine has antibiotic and bacteriostatic  properties. For millennia it has been used to bathe wounds, and a recent study, when surface wounds were so treated in a hospital emergency room, has confirmed its anti-infective property. Wine is almost always pure and  hygienic as far as bacterial contamination is concerned and is a safe beverage for travellers warned not to drink local water."

-----Paul Scholten, M.D., from Wine and Health, published 1997 by the  International Wine & Food Society

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