Forum Comments
Background: A large percentage of observational prospective studies have shown that women who consume alcohol show an increase in their risk of developing breast cancer. In general, the relation seems to be stronger for women who drink in binges, are also taking post-menopausal hormonal therapy, and/or have low intakes of dietary folate. Most studies have shown that heavier drinkers are at the greatest risk.
The present analysis is from the Nurses’ Health Study, which is one of the first prospective studies to point out an association between alcohol consumption and breast cancer. It attempts to determine if both the amount of alcohol and the frequency of drinking affect risk, and also whether the cumulative alcohol intake over the adult years relates to the risk of breast cancer.
Comments on present paper: As is usual from the Nurses’ Health Study, the present analyses are very well done. Theoretically, the repeated assessments of consumption over time should provide a better estimate of long-term alcohol intake. It is interesting, however, that in these analyses, the risks of cancer associated with alcohol were almost the same whether based on the amounts of alcohol consumed at baseline in 1980 or on the cumulative average based on repeated assessments of intake through the years.
When adjusting for the cumulative lifetime consumption, there was no effect of the frequency of consumption (1-2, 3-4, or 5-7 days per week). This is different from the usual findings for the association between alcohol intake and cardiovascular disease, where more frequent intake is associated with greater protection.
Again, when adjusting for cumulative intake, there was only a weak relation with cancer from the reported maximum number of drinks per day; While there was not a clear trend, the highest risk ratio (RR = 1.21, CI 0.99-1.47) was for women reporting 6 or more drinks/day.
Both for the reported intake between ages 18 and 40 (based on recall) and the intake after age 40, the adjusted estimate of cancer risk showed a sharp increase at 10-19.9 g/day, although an increase in risk was present to a lesser degree in both age groups at 5 – 9.9 g/day. There was little difference in the effects of intake before 40 years and intake thereafter. No differences in association with breast cancer risk were seen according to type of beverage consumed.
Several reviewers pointed out that observational studies report “associations,” and often provide hypotheses to explain their findings; but “causation” cannot be proved from such studies alone. As one Forum reviewer stated: “The authors correctly present data as associations. Sometimes, the general population, health authorities, and the media automatically assume that an association clearly identifies a cause, and often advise very stringent measures based on such observational data.”
Modification of breast cancer risk associated with alcohol consumption by folate: A primary concern of several Forum reviewers was that the investigators did not evaluate folate intake as a potential confounder, even though the Nurses’ Health Study has extensive dietary data on its subjects. Previous reports from this study suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced (or eliminated) by adequate folate intake.1,2 These investigators had previously reported that the risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 μg/d (for alcohol intake >15 g/d versus less than 15 g/d, multivariate RR 1.32, CI 1.15-1.50). For women who consumed at least 300 μg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol versus less than 15 g/d was 1.01 (CI 0.92-1.20).
Similarly, Baglietto et al3 reported that the estimated hazard ratio for breast cancer of an alcohol consumption of 40 g/day or more was 2.00 (CI 1.14-3.49) for women with intakes of 200 μg/day of folate and 0.77 (0.33-1.80) for those with intakes of 400 μg/day of folate. Further, Beilby et al4 observed marked reductions in odds ratios for breast cancer among women with higher levels of serum folate, as have many others.5-10
Tjønneland et al11 also reported that an association between alcohol intake and risk of breast cancer was present mainly among women with low folate intake. A RR of 1.19 (CI 0.99-1.42) per 10 g average daily alcohol intake was found for women with a daily folate intake below 300 μg, while among women with a folate intake higher than 350 μg, they could not show an association between the alcohol intake and the breast cancer incidence rate (e.g., for folate intake >400 μg, the RR was 1.01, CI 0.85-1.20). On the other hand, Feigelson et al12 found no evidence of an interaction between levels of dietary folate and alcohol and associations with breast cancer risk.
One reviewer stated: “This is a well conducted cohort study, with good assessment of the exposure variable and good assessment of the outcome variable. While a number of potential confounders have been considered and controlled for, it is unfortunate that diet as a potential confounder has not been taken into account.”
Another reviewer commented: “The results are plausible from the pathophysiological point of view: alcohol intake increases estrogen levels and this means that women have a slightly lower risk for osteoporosis and a slightly higher risk for breast cancer. When we tell the public that current data suggest small to moderate amounts of alcohol protect against cardiovascular disease, osteoporosis, diabetes mellitus, and vascular dementia, we should also state that breast cancer risk in women is slightly increased.”
He adds that the authors of this paper put their findings into perspective when they conclude: “An individual will need to weigh the modest risks of light to moderate alcohol use on breast cancer development against the beneficial effects on cardiovascular disease to make the best personal choice regarding alcohol consumption.”
