ALCOHOL USE AND OBESITY LINKED TO INCREASED BREAST CANCER RECCURENCE

September 1, 2010 — Studies examining the relation between alcohol consumption and breast cancer have been decidedly mixed. But a paper published online August 30 in the Journal of Clinical Oncology reports that alcohol consumption appears to increase the risk for breast cancer recurrence.

"Clinicians should advise their breast cancer patients to possibly limit their consumption of alcohol," lead author Marilyn Kwan, PhD, a research scientist at Kaiser Permanente in Oakland, California, told Medscape Medical News. However, the data also suggest possible cardioprotective benefits associated with alcohol consumption, and Dr. Kwan acknowledged that the evidence can be difficult for patients to interpret.

"The most important advice I can give breast cancer patients is to talk with their clinician about any lifestyle changes they are considering after being diagnosed with breast cancer," Dr. Kwan said. "She can then fully evaluate the risks and benefits of consuming alcohol, and at what amount."

New Study Increases Evidence Base

"Our study increases the limited and mixed evidence base to date regarding the role of alcohol consumption and breast cancer prognosis; namely, that drinking moderate to heavy amounts of alcohol after a breast cancer diagnosis can possibly increase the risk of having a recurrence of breast cancer and dying from breast cancer," Dr. Kwan said.

"We found that alcohol negatively affects the prognosis of all women diagnosed with early-stage invasive breast cancer who consume at least 3 or 4 drinks per week, compared with women who did not consume any alcohol," she told Medscape Medical News.

The associations appeared stronger in overweight and/or postmenopausal women, which perhaps indicates that women in these subgroups are more susceptible to the effects of alcohol, she noted.

"Alcohol has been shown to increase estrogen metabolism and circulating estrogen levels in postmenopausal women, while being obese can also increase circulating sex hormones and insulin levels," Dr. Kwan explained. "In general, an overabundance of estrogen production can lead to breast cell proliferation and possible carcinogenic events in the breast tissue."

There was no association between alcohol intake and all-cause death. The authors note, however, that alcohol intake was possibly associated with a decreased risk for nonbreast cancer death, which would be consistent with current literature on "alcohol's likely protective effects on cardiovascular-related outcomes."

Elucidates a Mystery in the Literature

In an accompanying editorial, Michelle D. Holmes, MD, DrPH, from Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, notes that early detection and modern treatments have dramatically improved the prognosis for women with early-stage breast cancer.

"Clearly, women with breast cancer are living long enough to be vulnerable to death as a result of cardiovascular disease, which is still the number one cause of death among US women," she writes.

The study is important, she notes, because it "elucidates a mystery in the literature" concerning lifestyle factors that appear to affect breast cancer survival. The data in this study showed the "expected decrease in survival when recurrence and breast cancer death were used as end points, and no decrease in overall survival with alcohol intake," Dr. Holmes writes.

The study is also important because of the guidance it can give to individuals living with breast cancer and their physicians, she adds. "Their decision is the same as that facing woman without breast cancer; the answer is not a clear-cut yes or no."

"Moderate consumption of alcohol is likely to increase a woman's risk of dying as a result of breast cancer while decreasing her risk of dying as a result of heart disease," Dr. Holmes notes. "Whether to consume alcohol is an individual decision and is dependent on each woman's evaluation of and comfort level with those risks."

Strongest Effect Seen in Subgroups

In the study, Dr. Kwan and colleagues evaluated the association between alcohol and recurrence and mortality among early-stage breast cancer survivors. The prospective study consisted of 1897 women diagnosed with invasive early-stage breast cancer from 1997 to 2000 who were participating in the Life After Cancer Epidemiology (LACE) study.

Wine was the most common beverage among those who consumed alcohol (88.5%), followed by liquor (42.1%) and beer (35.7%); the median amount of alcohol consumed was 5.96 g/day. Within this cohort, women who were postmenopausal, normal weight, and estrogen-receptor (ER) positive tended to consume more alcohol than those who were premenopausal, overweight/obese, and ER-negative.

As of September 8, 2009, there were 293 breast cancer recurrences (of which 71.9% were distant metastases) and 273 deaths. Of the deaths that occurred, 154 (56.4%) were attributable to breast cancer, 24 (8.8%) to other cancers, 32 (11.7%) to cardiovascular causes, and 63 (23.1%) to other causes. Overall, the average follow-up time was 7.42 years (range, 0.11 to 9.62 years).

After adjustment for confounders such as age at diagnosis, prediagnosis body mass index (BMI), total folate intake, stage of disease, hormone-receptor status, tamoxifen use, treatment, and positive lymph nodes, the researchers found that consuming 6 g or more of alcohol per day, compared with no drinking, was possibly associated with an increased risk for breast cancer recurrence (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.00 - 1.83) and breast cancer mortality (HR, 1.51; 95% CI, 1.00 - 2.29).

Drinking at least 2 servings of wine per week, compared with no wine, was also associated with an increased risk for disease recurrence (HR, 1.33; 95% CI, 0.97 - 1.81) and breast cancer death (HR, 1.37; 95% CI, 0.88 - 2.14), but a clear association was not seen for liquor or beer.

The data also suggest that alcohol consumption is associated with a decreased risk for death from causes unrelated to breast cancer (for less than 6 g/day, HR, 0.73; 95% CI, 0.45 - 1.20; for 6 g/day or more, HR, 0.77; 95% CI, 0.47 to 1.27).

The authors observed no association between overall death and drinking 6 g or more of alcohol per day.

When stratified by menopausal status, prediagnosis BMI, ER status, and risk for recurrence/breast cancer death, they found an association between consuming 6 g or more of alcohol per day with an increased risk for recurrence (HR, 1.51; 95% CI, 1.05 - 2.19) and breast cancer death (HR, 1.72; 95% CI, 1.05 - 2.81) among postmenopausal women. There was also a positive dose-response for greater alcohol intake and increasing risk (P for trend = .03 and .04, respectively).

No association was observed for premenopausal women.

Similarly, an association was seen among overweight and obese women, who had an increased risk for recurrence (HR, 1.60; 95% CI, 1.08 - 2.38) and an elevated but nonsignificant risk for breast cancer death (HR, 1.61; 95% CI, 0.94 - 2.76), with a positive dose-response (P for trend = .03 and .09, respectively).

Among women of normal weight, no associations were observed. The authors note that no difference in risk for recurrence or breast cancer death by ER status was observed for alcohol intake.

The study was supported by a grant from the National Cancer Institute. The authors and editorialist have disclosed no relevant financial relationships.

J Clin Oncol. Published online August 30, 2010.