To Your Health: How Does the Latest Research on Alcohol and Breast Cancer Inform Clinical Practice?

In 1977, a report was published from data collected by the Third National Cancer Survey, which found significant associations between alcohol intake and increased risk of cancers of the oral cavity, larynx, esophagus, colorectum, and unexpectedly, cancer of the breast. Subsequent research and meta-analyses have found that alcohol intake is significantly associated with breast cancer risk, with relative risk (RR) estimates suggesting relative increases in risk that range from 5% to 11% with light drinking (ie, up to one drink or 10 g. of alcohol per day) and 22% to 40% with quantities of two to three drinks per day. The risk of alcohol use appears greater with more recent exposure (ie, later versus early adulthood), and for cancers that are estrogen receptor (ER) positive, and that occur after menopause, although there is no agreement as to whether the source of alcohol (beer, wine, or spirits) is a significant factor or not. Of concern, it has been suggested that hormone replacement therapy (HRT), obesity, and low folate status interact with alcohol intake and further exacerbate risk. Biologically, alcohol is thought to promote breast cancer development through the upregulation of aromatase, with resulting increases in estrogen levels which act on breast tissue either directly or via the ER. Other potential mechanisms may include oxidative stress with enhanced formation of DNA adducts, increased exposure to acetaldehyde, epigenetic changes due to altered methyl transfer, and decreased retinoic acid concentrations associated with a modified cell cycle. Given the centrality of these mechanisms—especially that of estrogen—to the growth of breast cancer, the potential contribution of alcohol intake to breast cancer prognosis has been an area of interest for women diagnosed with breast cancer, and the clinicians who treat them. Questions such as “Does my drinking history predict the course of my disease and overall health?” and “Must I now abstain from alcohol?” are common concerns addressed in the dialogue between patient and provider. The findings of Newcomb et al in the article that accompanies this editorial provide some reassurance that a history of alcohol use before, or after, breast cancer diagnosis does not seem to adversely affect survival. They studied the association of prediagnostic alcohol intake with breast cancer–specific and overall survival in 22,890 patients with breast cancer enrolled onto the Collaborative Women’s Longevity Study; they also examined the association of postdiagnosis intake with outcomes in a subset of 4,881 women who provided information an average of 5.7 years after diagnosis. In analyses adjusting for age, stage, body mass index, smoking, mammography, and several breast cancer risk factors there was evidence of a curvilinear association of preand postdiagnostic alcohol intake with mortality. Compared with nondrinkers, women who were modest alcohol drinkers before breast cancer diagnosis (three to six drinks per week) had a 15% relative reduction in breast cancer–specific mortality while those who consumed up to nine drinks per week had a 25% to 30% relative reduction in death from cardiovascular disease and a 15% to 25% relative reduction in death from any cause. More importantly, because cancer survivors can modify post(but not pre-) diagnosis alcohol consumption, moderate alcohol consumption after diagnosis (one to nine drinks per week) was not significantly associated with death from breast cancer but was associated with 40% to 50% relative reduction in cardiovascular mortality and a 10% to 15% relative reduction in all-cause mortality. These results are consistent with previous findings of Flatt et al, who reported similar reductions in overall mortality (hazard ratio [HR], 0.69; 95% CI, 0.49 to 0.97) among survivors of breast cancer (n 3,088) who regularly consumed alcohol after diagnosis while participating in the Women’s Healthy Eating and Living (WHEL) study. Although an early study by Kwan et al of 1,897 survivors of breast cancer participating in the Life After Cancer Epidemiology (LACE) study also found evidence of cardiovascular benefit for postdiagnosis alcohol consumption, a concern was raised about an elevated risk for breast cancer recurrence (HR, 1.35; 95% CI, 1.00 to 1.83) and breast-cancer specific death (HR, 1.51; 95% CI 1.00 to 2.29) among drinkers. More recent findings in an expanded LACE cohort (n 9,329) identified reduced cardiovascular mortality without increases in either recurrence or in breast cancer–specific mortality among drinkers. Together, these data are reassuring and they lend support to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Survivors (Table 1). With the release of the original ACS “Guide for Informed Choices on Nutrition and Physical Activity During and After Cancer Treatment,”; and with subsequent updates, including the most recent “ACS Guidelines on Nutrition and Physical Activity for Cancer Survivors,”; expert panels have carefully considered recommendations related to alcohol consumption. This is a complex task because alcohol is associated with increased risk of several cancers, yet many cancer survivors are at significantly greater risk for cardiovascular JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 31 NUMBER 16 JUNE 1 2013

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