Critique 018 Alcohol intake after diagnosis of early-stage breast cancer may increase subsequent risk of recurrence but not risk of subsequent mortality September 14, 2010

Kwan ML, Kushi LH, Weltzien E, Tam EK, Castillo A, Sweeney C, Caan BJ.  Alcohol Consumption and Breast Cancer Recurrence and Survival Among Women With Early-Stage Breast Cancer:The Life After Cancer Epidemiology Study.   J Clin Oncol 2010;28 (published ahead of print, 10.1200/JCO.2010.29.2730)

Authors’ Abstract

Purpose  To examine the association of alcohol consumption after breast cancer diagnosis with recurrence and mortality among early-stage breast cancer survivors.

Patients and Methods  Patients included 1,897 LACE study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited on average 2 years postdiagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry.  Alcohol consumption (i.e., wine, beer, and liquor) was assessed at cohort entry using a food frequency questionnaire.  Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% CI with adjustment for known prognostic factors.

Results  Two hundred ninety-three breast cancer recurrences and 273 overall deaths were ascertained after an average follow-up of 7.4 years.  Nine hundred fifty-eight women (51%) were considered drinkers (≥ 0.5 g/d of alcohol), and the majority drank wine (89%).  Drinking ≥ 6 g/d of alcohol compared with no drinking was associated with an increased risk of breast cancer recurrence (HR, 1.35; 95% CI, 1.00 to 1.83) and death due to breast cancer (HR, 1.51; 95% CI, 1.00 to 2.29).  The increased risk of recurrence appeared to be greater among postmenopausal (HR, 1.51; 95% CI, 1.05 to 2.19) and overweight and obese women (HR, 1.60; 95% CI, 1.08 to 2.38).  Alcohol intake was not associated with all-cause death and possibly associated with decreased risk of non–breast cancer death.

Authors’ Conclusion  Consuming three to four alcoholic drinks or more per week after a breast cancer diagnosis may increase risk of breast cancer recurrence, particularly among postmenopausal and overweight/obese women, yet the cardioprotective effects of alcohol on non–breast cancer death were suggested.

Forum Comments

Previous research on topic:  Whether alcohol consumption in a woman who has been diagnosed with breast cancer affects her subsequent course is unclear.  A paper from Reding et al1 from the Fred Hutchinson Cancer Research Center in Seattle, WA, reported that women who consumed alcohol before a diagnosis of breast cancer had improved survival.  Barnett et al2 reported on more than 4,000 women with invasive breast cancer who had taken part in the Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) project, and showed a lower risk of death among women “currently consuming” 7 or more drinks/week versus < 7 drinks/week.  Another previous large study of 3,088 early-stage breast cancer survivors found that neither light nor moderate drinking following a diagnosis of breast cancer was associated with recurrence of breast cancer, but moderate intake lowered overall mortality3.  In that study, compared with women of normal weight, obese women had a tendency to have higher mortality (HR=1.28, 95% CI 0.97 – 1.70); ever smokers had higher morality risk than never smokers (HR=1.32, 1.04 – 1.66), as did nulliparous women versus parous women (HR = 1.37, 1.05 – 1.79)3. 

Among the limited number of studies with alcohol data collected after the diagnosis of breast cancer, Li et al4 found an increase in the development of a primary cancer in the contralateral breast among women who were smokers and consumed 7 or more drinks per week4.  On the other hand, no relation of alcohol consumption with overall mortality among breast cancer survivors was seen in several other past studies.  In the Nurses’ Health Study, for example, moderate alcohol intake after a diagnosis of breast cancer was not associated with overall mortality among 1,982 women observed for 13.1 years5.  In that study, there was a tendency for poorer survival among current smokers and obese women, although interactions with alcohol were not reported5.  In another prospective cohort study of 1,453 patients with breast cancer observed for 12.6 years in Italy, no association was observed between overall alcohol drinking or wine drinking within 1 year after diagnosis and risk of overall death and breast cancer death6,7.

Comments on present study:  In the present prospective study of 1,897 women with early-stage breast cancer from the Kaiser Permanente Study, alcohol intake assessed at two years after diagnosis was related to subsequent recurrence of breast cancer and breast-cancer death during follow up averaging 7.4 years.  The authors concluded that consumption of 3 to 4 or more drinks per week increased the risk of recurrent disease and breast-cancer mortality.  For this group, mean intake was 12 grams/day (about one typical US drink) and the median intake was 6 grams/day, about one half of a typical drink.

An appropriate food-frequency questionnaire was used to collect alcohol data, and typical serving size was noted.  For all alcohol, servings per day in ounces was converted to grams per day of alcohol, using 13.7 grams for a typical drink.  Subjects were categorized into the following consumption categories: none (≤ 0.5 g/d, the lowest category of intake, nondrinkers), 0.6 to 5.0 g/d (occasional drinkers), and ≥ 6 g/d (regular drinkers).  However, given the distribution of alcohol consumption, it will be difficult to compare the results of this study to European cohort studies, where consumption levels tend to be much higher2,6,7.  Further, generalizability of the results may be limited by the fact that of women with a diagnosis of breast cancer who were recruited for the study, only 46% agreed to take part. 

As the authors stated, “The associations appeared stronger among postmenopausal women and overweight/obese women . . . suggesting that the effects of alcohol might be specific to certain subgroups of women previously diagnosed with breast cancer.  Alcohol intake was associated with a possible decreased risk of death from non–breast cancer causes, consistent with literature on alcohol’s likely protective effects on cardiovascular-related outcomes.  Overall, no association was observed with all-cause death.”  There were few current smokers in the study, and no comment was made on the effect that smoking may have had on the risk of recurrent breast cancer.

A shortcoming of this study could relate to the authors’ inclusion of a very homogenous Utah patient population that generally does not consume alcohol and might carry its own risk factors for breast cancer and recurrence.  The present study does not permit an evaluation of genetic factors that might affect recurrent disease such as BRCA genes or those affecting alcohol metabolism.  The study supports previous findings that obesity carries with it unique risks for all forms of cancer, cancer recurrence, and survival. 

In the present study, data were not available regarding alcohol intake prior to the diagnosis of breast cancer.  There are always questions whether breast cancer that develops among women who consume alcohol (which has been shown to increase risk) differs from breast cancer that develops among women who are lifetime abstainers.  In general, it would be expected that those who did not drink alcohol before the diagnosis would not begin drinking after the diagnosis, but some alcohol consumers may have stopped drinking.  It is always difficult to know whether some type of adjustment in the analyses should be made for alcohol intake prior to the diagnosis of breast cancer.

The lack of data on lifetime abstainers and former drinkers might have underestimated the relation between alcohol and overall mortality; sicker women may have been less likely to drink (lower proportion of stage I and higher proportion of mastectomy in low alcohol group).  In addition, sicker women may have stopped drinking within the 2-year window in which alcohol was assessed.  If alcohol intake were positively associated with recurrent breast cancer, then contaminating never drinkers with former drinkers would attenuate the relation between alcohol and recurrent breast cancer.  Stronger effects among obese women might suggest interaction between adipokines and alcohol on the risk of recurrent breast cancer (not evaluated in this paper).

Overall, what should be emphasized in this study is what we already know about all cancers: obesity carries with it unique risks for all forms of cancer, cancer recurrence, and survival, and alcohol is generally found to be associated with a modest increase in risk.  Furthermore, the data also show that women with breast cancer are still more likely to succumb to illnesses other than breast cancer, conditions for which moderate alcohol consumption has proven benefit in limiting morbidity and mortality. 

Summary:  The present study was based on a large number of women with generally early-stage breast cancer who were followed for an average of 7.4 years.  It found an increase in risk of breast cancer recurrence and breast cancer death, but no effect on total mortality, to be associated with consumption of 3 to 4 or more drinks per week.  Previous research has been mixed on this topic.  Almost all large studies have shown no increase in total mortality for women who drink moderately following a diagnosis of breast cancer.  As for recurrence of breast cancer, most have shown no increase in risk, although one previous study of women with estrogen-receptor + tumors found an increased risk of a primary cancer developing in the contralateral breast to be associated with alcohol intake of more than 7 drinks per week.  Further research will be required to determine the extent that alcohol intake following a diagnosis of breast cancer affects a woman’s subsequent morbidity and mortality.

References from Forum Review

  1. Reding KW et al, Effect of prediagnostic alcohol consumption on survival after breast cancer in young women.  Cancer Epidemiol Biomarkers Prev 2008;17:1988-1996.
  2. Barnett GC et al, Risk factors for the incidence of breast cancer: Do they affect survival from the disease?  J Clin Oncol 2008;26:3310-3316. 
  3. Flatt SW, Thomson CA, Gold EB, et al: Low to moderate alcohol intake is not associated with increased mortality after breast cancer. Cancer Epidemiol Biomarkers Prev 2010;19:681-688.
  4. Li CI, Daling JR, Porter PL, et al: Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptorpositive invasive breast cancer. J Clin Oncol 2009;27:5312-5318.
  5. Holmes MD, Stampfer MJ, Colditz GA, et al: Dietary factors and the survival of women with breast carcinoma. Cancer 1999;86:826-835.
  6. Dal Maso L, Zucchetto A, Talamini R, et al: Effect of obesity and other lifestyle factors on mortality in women with breast cancer. Int J Cancer 2008;123:2188-2194.
  7. Franceschi S, Dal Maso L, Zucchetto A, et al: Alcohol consumption and survival after breast cancer. Cancer Epidemiol Biomarkers Prev 2009;l8:1011-1012.

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Contributions to this critique by the International Scientific Forum on Alcohol Research were from the following members:

Luc Djoussé, MD, DSc, Dept. of Medicine, Division of Aging, Brigham & Women’s Hospital and Harvard Medical School, Boston, MA, USA 

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

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

Lynn Gretkowski, MD, Obstetrics/Gynecology, Mountainview, CA, Stanford University, Stanford, CA, USA

Yuqing Zhang, MD, DSc, Epidemiology, Boston University School of Medicine, Boston, MA, USA