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Abstract

OBJECTIVE:

To determine the association of prediagnostic alcohol consumption with long-term mortality from breast cancer and other causes in a cohort of women with breast cancer.

METHODS:

We studied a Michigan-based cohort of 939 women aged 40–84 years, who provided complete information about the type, amount and intensity of prediagnostic alcohol consumption. Associations of alcohol consumption, based on weekly volume of alcohol consumption during the year prior to breast cancer diagnosis, with mortality were evaluated in Cox proportional hazards models, with adjustment for sociodemographic factors, body mass index, smoking, comorbidity, tumor characteristics, and treatment. Differences among covariates were assessed with Pearson χ² , Student t -tests and Wilcoxon Rank Sum tests. All statistical tests were two-sided.

RESULTS:

During a median follow-up of 11 years, 724 deaths occurred overall, with 303 from breast cancer. Fifty-five percent of the women were categorized as drinkers with volume of alcohol consumption ranging from 0.75 to 36.00 drinks/week. In multivariable models, a decreased risk of other-cause mortality was associated with low alcohol drinking (0.75–3.75 drinks/week; HR = 0.61, 95% CI = 0.47–0.78), moderate volume alcohol drinking (4.00–9.75 drinks/week; HR = 0.57, 95% CI = 0.39–0.85) and low frequency (0.75–3.75 drinks/week) beer and wine intake (HR = 0.69, 95% CI = 0.50–0.96 and HR = 0.68, 95% CI = 0.52–0.88 respectively). Although the risk of breast cancer-specific mortality was not statistically significantly associated with moderate (4.00–9.75 drinks/week) and high volume (10.00–36.00 drinks/week) alcohol drinking in the overall cohort (HR = 1.43, 95% CI = 95% 0.97–2.12 and HR = 1.53, 95% CI = 0.87–2.70 respectively), there was a positive association of alcohol consumption with breast cancer-specific mortality among current smokers (HR = 1.92, 95% CI = 1.03–3.57; P _interaction = 0.04).

CONCLUSION:

In this prospective cohort study, regular consumption of 0.75–36.00 alcoholic drinks per week during the year prior to breast cancer diagnosis was associated with a reduction in other-cause mortality and with an increase in breast cancer-specific mortality among current smokers, after taking into account clinical and sociodemographic factors.

Keywords

Breast cancer mortality alcohol consumption prospective cohort study

Introduction

Breast cancer is the second highest cause of cancer mortality in U.S. women after lung cancer [1]. Alcohol has been implicated as a modifiable risk factor for breast cancer [2], but the evidence on the association between alcohol intake and mortality among breast cancer survivors is inconsistent [3,4]. Consumption of alcohol was found to be associated with other-cause mortality, breast cancer-specific mortality and all-cause mortality in several studies [5–7]. Whereas some studies reported no association with all-cause mortality [7–11], other reports showed an inverse association between alcohol consumption and overall survival [6,12,13]. In addition, evidence on the association of alcohol consumption with breast cancer recurrence is inconsistent, with some studies reporting an increased risk of recurrence with increased alcohol intake, [7,14,15] and others reporting no association [13,16]. This inconsistent evidence may be explained by the heterogeneity of study populations and methodological limitations, including, low sample size [10,17] and measurement of alcohol consumption as well as low alcohol consumption in certain study populations [6,7,12,13,18,19].

Frequent alcohol intake was also found to be associated with advanced breast cancer stage [20] but the extent to which the impact of prediagnostic alcohol intake on mortality among women with breast cancer may differ according to the extent of disease and smoking status is not well defined. Evaluating such relationships may help estimate the long-term consequences of alcohol intake and might justify and focus targeted interventions that are intended to improve health and life span of breast cancer survivors.

In this study of the long-term prognostic role of alcohol consumption, we considered death from breast cancer and other causes for women in a population-based cohort of breast cancer survivors, Health and Functioning in Women (HFW) [21–23]. Women with incident breast cancer in the HFW cohort were followed for a median of 11 years since diagnosis in the Detroit, Michigan area in the United States. By including both middle-aged and elderly women with breast cancer, this cohort of breast cancer survivors was suitable for examining the consequences of prediagnostic alcohol consumption while taking into account known prognostic factors in the clinical, lifestyle-related, and sociodemographic domains. We evaluated the extent to which the impact of alcohol consumption on mortality differed as a function of smoking status and tumor stage.

Methods

Study population

We present data from the HFW study, which was founded in 1984 in the Detroit metropolitan area to evaluate the health, functional, and psychosocial status of women following diagnosis of breast cancer as described previously [21–24]. An overall of 1,011 eligible participants, aged between 40 and 84 years, had histologically confirmed, primary invasive breast cancer, identified through the Metropolitan Detroit Cancer Surveillance System (MDCSS) at the Michigan Cancer Foundation (Barbara Ann Karmanos Cancer Institute), within 4 weeks of diagnosis. Participants were interviewed in two cohorts. The first cohort was of 571 participants aged 55–84 (recognized over a 7-month period between 1984 and 1985), 463 (81.1%) were interviewed between 2 and 4 months following diagnosis. The second cohort was of 620 cases, aged 40–54 and 74–84 (recognized over a 7-month period between 1987 and 1988), 548 (88.4%) were interviewed between 2 and 4 months after diagnosis, henceforward referred to as the baseline interview. All participants were interviewed a second time approximately 9 months after the first interview [24]. The two cohorts were combined, and 939 women with complete data available on alcohol consumption and all major covariates were included in these analyses.

Assessment of alcohol consumption

Alcohol consumption was determined from the baseline questionnaire after breast cancer diagnosis, as described previously [20]. Briefly, three different alcohol exposure parameters were used: type (beer, wine and other alcohol drinks), amount (the quantity of drink) and intensity (number) of drinks [20]. Interviews were conducted by trained staff over 2–4 months period following breast cancer diagnosis. The first alcohol-related question was: “Thinking of 1 year ago, have you consumed any beer, wine or other alcohol beverages?”, which was evaluated as a binary (yes/no) variable. The second question was “how often did you drink (Name of beverage)?” The third question was, “On the days that you drank (Name of beverage), how many glasses did you usually have?” For wine, beer and other alcohol drinks, participants marked frequency of consumption and specified the serving size as the number of glasses of drink and servings per week as “never, less than once a week, once or twice a week and more than twice a week”. The participant categories for the frequency of consumption were weighted as: “never, 0; less than once a week, 0.5; once or twice a week, 1.5; and more than twice a week, 3.0”. The quantity of consumption was weighted as follows: “1 or 2 glasses, 1.5; 3 or 4 glasses, 3.5; and 5 or more glasses, 6.0”. The frequency and quantity weights were multiplied to create a summary measure for each beverage types: beer, wine and other alcohol and the total number of drinks consumed per week was obtained by summing the contribution from each beverage type. Using this method, we derived a variable of overall alcohol consumption of participants per week. This variable was used relative to categories of reported weekly alcohol consumption one year prior to the interview and based on categories previously used by Hilton and Clark [25]. Those who did not drink alcohol 1 year prior to the interview were described as non-drinkers; those who drank less than 4 drinks/week as low alcohol drinkers; those who drank 4–10 drinks/week as moderate drinkers; and those who drank >10 drinks/week as high alcohol drinkers. A drink was considered equal to 12 oz of beer, 4 oz of wine and 1.5 oz of other alcohol. An average of 13 g of alcohol/drink was used in the study based on the fact that alcohol content of beer, wine and other alcoholic beverages ranges from 10.97 to 17.9 g of alcohol/glass as described previously [20,25]. The baseline questionnaire also elicited information on other breast cancer risk factors including personal history, sociodemographic and lifestyle variables.

Covariates

The covariates in these analyses were sociodemographic, lifestyle-related and clinical prognostic factors that, based on existing literature and a priori hypotheses, could potentially confound or modify an association between alcohol consumption and mortality. The covariates included were: age at diagnosis, race (White or African–American), breast cancer stage (local, regional or remote), surgery (no surgery, partial mastectomy or modified radical mastectomy), type of adjuvant cancer treatment (radiation or chemotherapy), education (less than high school, high school, college or graduate), smoking status (never, former and current smokers), body mass index (kg/m² ), number of positive lymph nodes involved (0 nodes, 1–3 and ≥4 nodes), tumor size, co-morbidity, and financial adequacy (adequate or inadequate), which was measured based on self-reported current financial resources and whether they met the participant’s needs [24,26]. BMI was derived from self-reported weight and height at the baseline interview. A comorbidity index was constructed from the respondent’s diagnosed conditions reported by the respondent at the baseline interview from a list of 23 conditions that included diabetes, hypertension, stroke, heart disease, gastrointestinal disease, liver conditions, and primary cancers other than breast cancer, which according to the respondents, currently caused restriction of her usual activities [22,24,26]. In addition to information on surgery and type of adjuvant therapy (radiation or chemotherapy) provided by the MDCSS files, physicians completed a supplementary survey regarding chemotherapy and hormonal therapy administered on an outpatient basis. The data from the two sources were combined to create a two-level treatment variable (no surgery or partial mastectomy and modified radical mastectomy) [22,24]. Marital status was coded as never married, separated/divorced, widowed or married. Adequacy of medical insurance was measured in terms of adequacy of insurance in meeting one’s needs (inadequate coverage or adequate coverage).

Ascertainment of outcomes

In the HFW study, participants were followed until last contact (April 2012) or death, whichever occurred first. Vital status of participants–date and cause of death–was determined through annual vital status surveillance of all patients in the registry, conducted by MDCSS [21,26]. International Classification of Diseases (ICD) codes (version 9), 174.0–174.9 were noted for breast cancer deaths and other ICD codes represented death from causes other than breast cancer referred henceforth as other-cause mortality. The cause of death was available for all participants that died and the vital status assessment of all participants was complete.

Statistical analysis

Differences in means and proportions of each potential covariate between drinking and non-drinking women were compared using Student’s t -test for continuous variables and Pearson’s χ2 test for categorical variables. Differences in sample medians were assessed using Wilcoxon Rank Sum test. Kaplan–Meier plots were used to examine the multivariate association between alcohol consumption and survival.

We used Cox proportional hazard models stratified by age at breast cancer diagnosis with time since diagnoses as the time scale were used to estimate the association between alcohol consumption and other-cause and breast cancer mortality. We interpreted the Cox proportional hazard models by examining crude and adjusted hazard ratios (HRs) and 95% confidence interval (CI) for events in relation to alcohol consumption. The proportionality of hazards assumption was assessed using Schoenfeld residuals, revealing no significant departures from proportionality [27]. For analyses involving breast cancer-specific mortality, participants who died from other causes were censored at the time of their death. Breast cancer treatment, stage at diagnosis, race/ethnicity, smoking status, body mass index, financial adequacy, education, positive lymph node involvement, tumor size at diagnosis, comorbidity, and period of study entry were considered as potential confounders in all multivariate analyses. To assess effect modification by tumor stage at diagnosis, we conducted subgroup analyses (local versus regional/distant stage). We combined women in regional and distant or remote stage due to a small number of women with distant stage disease (n = 53). In multivariable models of alcohol intake, interaction terms for smoking status and race were considered. For analyses, all p -values obtained were two-sided, with p -values less than 0.05 considered as statistically significant. Statistical analyses were conducted using the STATA statistical software package (version 12; StataCorp, College Station, TX).

Results

Baseline characteristics of the cohort by drinking status are given in Table 1. Mean age at the time of breast cancer diagnosis was 63 years [SD (standard deviation) = 12.5]. Overall, the median follow-up time after diagnosis was 11 years (interquartile range: 4.4–23.4 years). During this time, 724 deaths occurred, with 303 resulting from breast cancer and 421 from other causes. Approximately 46.6% of deaths in drinkers and 37.1% in non-drinkers were due to breast cancer. Other-cause mortality was found to be higher in non-drinkers (62.9%) than drinkers (53.4%). Compared to non-drinkers, drinkers (55%) were younger, had longer follow-up (14.3 years), were more educated (P = 0.0001) and were more likely to be former or never smokers (P < 0.0001). Mean BMI was 25.9 (S.D = 5.05) for drinkers and 26.8 (S.D = 5.5) for non-drinkers and there were statistically significant differences in BMI by drinking status (P = 0.008). A total of 57% of drinkers and 45% of non-drinkers were married and there were significant differences in marital status between drinkers and non-drinkers (P < 0.0001). Similarly, there were significant differences in the number of co-morbidities by drinking status; mean (S.D) for the number of comorbidities was 2.0 (S.D = 1.3) for drinkers and 2.4 (S.D = 1.7) for non-drinkers (P = 0.002). The majority of woman had localized (53.4%) and regional (41%) stage disease and only 5.6% had remote disease. There were differences in breast cancer treatment by drinking status, with 76.3% of the drinkers treated with modified radical mastectomy compared to 79.8% of non-drinkers (P = 0.02), 22.4% of drinkers treated with partial mastectomy compared to 16.9% of non-drinkers (P = 0.02), and 0.9% of drinkers treated with non-surgical treatment compared to 2.8% of non-drinkers (P = 0.03). However, there were no significant differences in the number of positive lymph nodes, tumor stage and size by drinking status.

Table 2 presents the association between overall alcohol intake and both breast cancer-specific and other-cause mortality in our analytic cohort. Nearly half of the cohort (45.9%) reported no alcohol consumption one year prior to the interview. Of drinkers, 37.6% and 12.4% reported low and moderate levels of alcohol consumption (0.75–3.75 and 4.00–9.75 drinks/week) respectively. Other-cause mortality was associated with low (0.75–3.75 drinks/week) and moderate (4.00–9.75 drinks/week) volume alcohol drinking after covariate adjustment (HR = 0.61,95% CI = 0.47–0.78 and HR = 0.57, 95% CI = 0.39–0.85 respectively). High alcohol intake (10.00–36.00 drinks/week) was not statistically significantly associated with other-cause mortality (HR = 0.60, 95% CI = 0.31–1.16). Risk of breast cancer-specific mortality was not statistically significantly associated with low (0.75–3.75 drinks/week), moderate (4.00–9.75 drinks/week) or high (10.00–36.00 drinks/week) volume alcohol drinking (HR = 1.01, 95% CI = 0.75–1.35; HR = 1.43, 95% CI = 0.97–2.12; HR = 1.53, 95% CI = 0.87–2.70, respectively).

Mortality from causes other than breast cancer

Kaplan Meier (KM) plots (Figs 1a, 2a, 3a) of other-cause survival revealed higher other cause survival with wine intake. Low, moderate and high wine intake resulted in higher other cause survival in drinkers than non-drinkers (Fig. 1a). Likewise, KM plots of other-cause survival indicated more favorable survival in low versus no beer consumers (Fig. 2a). With high frequency (10.00–36.00 drinks/week) of alcohol consumption, beer drinkers had a markedly shorter survival in the first 10 years of follow-up compared to the remaining groups.

Results from unadjusted and covariate-adjusted analyses of Cox models are presented in Table 3. Drinking beer in low frequency (0.75–3.75 drinks/week) was associated with a statistically significant decrease in the risk of other-cause mortality after covariate adjustment (HR = 0.69, 95% CI = 0.50–0.96). Likewise, low frequency wine drinking (0.75–3.75 drinks/week) was associated with a statistically significantly decreased risk of other-cause mortality (HR = 0.68, 95% CI = 0.52–0.88) in a covariate-adjusted model. High intake of other alcoholic drinks (10.00–36.00 drinks/week), was statistically significantly associated with decreased risk of other-cause mortality after covariate adjustment (HR = 0.54, 95% CI = 0.31–0.95).

Breast cancer-specific mortality

KM plots (Figs 1b, 2b, 3b) of breast cancer-specific survival reveal considerably shorter survival as the frequency of alcohol consumption increased. Moderate beer consumption (4.00–9.75 drinks/week) was not statistically significantly associated with an increased risk of breast cancer-specific mortality after covariate adjustment (HR = 1.65, 95% CI = 0.98–2.77) (Table 3). Low frequency wine consumption (0.75–3.75 drinks/week) was not statistically significantly associated with a decreased risk of breast cancer-specific mortality in the fully adjusted model (HR = 0.75, 95% CI = 0.55–1.03).

There was a statistically significant interaction between alcohol intake (abstaining versus drinking) and smoking status in relation to breast cancer-specific mortality in a fully adjusted Cox model (HR = 1.92, 95% CI = 1.03–3.57, P _interaction = 0.04). Consistent with this, the association between alcohol intake and breast cancer-specific mortality differed by smoking status among former and current smokers (HR = 0.96, 95% CI = 0.52–1.78 and HR = 1.92, 95% CI =1.03–3.57 respectively).

To better understand the association of alcohol intake, extent of disease and mortality, we next performed stratified analyses by tumor stage (Table 4). Low wine intake (0.75–3.75 drinks/week) was associated with statistically significantly decreased risk of other-cause and breast cancer-specific mortality in covariate-adjusted models (HR = 0.64, 95% CI = 0.45–0.89 and HR = 0.53, 95% CI = 0.29–0.96, respectively).

An increased risk of breast cancer-specific mortality was associated with high intake of wine (10.00–36.00 drinks/week) among women with regional/distant disease at diagnosis in adjusted models (HR = 2.24, 95% CI = 1.19–4.22; Table 4).

Discussion

In this prospective cohort of breast cancer survivors, we evaluated the association of prediagnostic alcohol use with breast cancer-specific and other-cause mortality. We examined whether the overall volume and frequency of alcohol consumption one year prior to the interview influenced breast cancer-specific mortality and other-cause mortality. Our results showed a positive association between alcohol intake and increased risk of breast cancer-specific mortality among current smokers. In contrast, low to moderate volume alcohol intake was associated with decreased risk of other-cause mortality. This finding is consistent with other studies that examined the association between alcohol consumption and other-cause mortality and breast cancer-specific mortality among women with breast cancer [16,28].

There are several putative biological mechanisms by which alcohol consumption could affect breast cancer outcomes. Alcohol may act through estrogen pathways that can proliferate via breast cancer cell lines [29]. Alcohol may also increase plasma estrogen levels by increasing the production of aromatases, which convert androgens to estrogens and also reduces the metabolism of estrogen in the liver, resulting in estrogen accumulation in blood [30]. Thus, female alcohol drinkers may experience elevated estrogen levels, which can in turn activate estrogen sensitive cells to become malignant [29]. Recent evidence also suggests that alcohol intake increases the risk of breast tumors characterized by estrogen and progesterone receptor positivity [29,31]. Moreover, Castro et al. [32] reported that the oxidative conversion of ethanol to acetaldehyde, a carcinogenic compound that generates free radicals, may play a role in breast carcinogenesis. Furthermore, women have greater physiological sensitivity to the effects of alcohol than men due to differences in alcohol metabolism; elevated postmenopausal estrogen levels in response to alcohol have been reported among women who consumed more than two drinks per day [33,34].

One of the strengths of our study is the ability to not only examine the association between alcohol consumption and mortality from breast cancer and other causes but also evaluate the effect modification by smoking status and tumor stage. The statistically significant effect modification by smoking status in this study may be due to the fact that smoking increases body’s harmful free radical load, consisting of toxic molecules of oxygen, with attendant decrease in anti-oxidant levels [35,36]. Castro et al. [32] also described a similar mechanism whereby the conversion of ethanol to acetaldehyde and other free radicals promoted carcinogenesis. An earlier analysis from the same HFW cohort that was used in the present analysis [20] also reported that smoking status and alcohol consumption were associated with breast cancer stage at diagnosis, a marker of disease severity and progression. These findings may inform patient recommendations and interventions aimed at improving survival [37].

Reding and colleagues suggested that wine, in particular, may reduce the risk of mortality among breast cancer survivors due to the presence of polyphenols, including resveratrol and cinnamic acid [6]. Other studies have also observed an association between decreased overall mortality and moderate red wine intake than beer or liquor drinkers [38], presumably due to its antioxidant effects of polyphenols, which include procyanidins and proanthocyanidins that offer cardioprotective effects [39,40]. This cardioprotective effect of red wine consumption may explain, to some extent, the observed decrease in other-cause mortality with light to moderate alcohol consumption.

One of the limitations of this study is that alcohol consumption status was self-reported at baseline interview after diagnosis. This study also did not have information about any changes in alcohol consumption that may have occurred after diagnosis. Our analyses examining the association of different alcoholic beverages with mortality are based on lower sample sizes and should, therefore, be considered exploratory. Data were also not available on dietary factors such as folate intake [10], which may modify the association of alcohol with mortality. This study also had no information on menopausal status and tumor markers such as estrogen/progesterone and human epidermal growth factor receptor 2 that could potentially modify the association between alcohol intake and risk of mortality among breast cancer survivors.

The strengths of this study include a prospective population-based cohort design, a relatively large set of White and African–American participants identified through a large regional, population-based surveillance program with long and complete follow-up of up to 28 years since diagnosis. Bias due to follow-up was minimized as mortality status was ascertained annually for all patients in the registry. Notably, there was a low likelihood of recall bias in this study since our cohort was composed of women who were incident rather than prevalent cases and interviewed 2–4 months following diagnosis about alcohol consumption during the preceding year. In addition, women who participated in this study had histologically and pathologically confirmed laboratory results. Also of significance is that this study utilized standardized and comprehensive measures of alcohol consumption as well as potential confounders in the sociodemographic and clinical domains that were assessed at the time of breast cancer diagnosis.

In summary, our findings indicate that in this prospective cohort study, alcohol consumption during the year preceding breast cancer diagnosis was associated with an important reduction in other-cause mortality and with an increase in breast cancer-specific mortality among current smokers, irrespective of clinical and sociodemographic factors. Our observations, combined with those of other investigators, point to the intricate relationship between alcohol consumption and longevity among breast cancer survivors. Future research with the same focus, wider range of alcohol consumption in large prospective cohort studies and longer follow-up are needed for further clarification.

Ethical considerations

The study was approved by the UCSF Committee on Human Research. Additionally, the Health and Functioning in Women (HFW) study was approved at the time of its establishment by the Human Subjects Committee at the Michigan Cancer Foundation.

Footnotes

Acknowledgements

This research was supported by grant # KG110940 from Susan G. Komen for the Cure and by grant # 121891-MRSG-12-007-01-CPHPS from the American Cancer Society (to Braithwaite). In addition, support was obtained from grant # R01-AG04969 from the National Institute on Aging (to Satariano), grant # PBR-67 from the American Cancer Society (to Satariano). We would also like to thank all women who participated in the study. We are grateful to Gloria Kwiatkowski and Fawn Vigneau from the Barbara Ann Karmanos Cancer Institute for their assistance with updating the mortality data.

Author’s disclosures of potential conflicts of interest

The authors indicated no potential conflicts of interest.

Funding

References

Lorigan

, Califano

, Faivre-Finn

, Howell

, Thatcher

, Lung cancer after treatment for breast cancer, Lancet Oncol, 11(12): 1184–1192, 2010.

Singletary

, Gapstur

, Alcohol and breast cancer: review of epidemiologic and experimental evidence and potential mechanisms, JAMA, 286(17): 2143–2151, 2001.

McTiernan

, Irwin

, Vongruenigen

, Weight, physical activity, diet, and prognosis in breast and gynecologic cancers, J Clin Oncol, 28(26): 4074–4080, 2010.

Patterson

, Cadmus

, Emond

, Pierce

, Physical activity, diet, adiposity and female breast cancer prognosis: a review of the epidemiologic literature, Maturitas, 66(1): 5–15, 2010.

Hebert

, Hurley

, Ma

, The effect of dietary exposures on recurrence and mortality in early stage breast cancer, Breast Cancer Res Treat, 51(1): 17–28, 1998.

Reding

, Daling

, Doody

, O’Brien

, Porter

, Malone

, Effect of prediagnostic alcohol consumption on survival after breast cancer in young women, Cancer Epidemiol Biomarkers Prevent, 17(8): 1988–1996, 2008, A publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

Kwan

, Kushi

, Weltzien

, Tam

, Castillo

, Sweeney

, Alcohol consumption and breast cancer recurrence and survival among women with early-stage breast cancer: the life after cancer epidemiology study, J Clin Oncol, 28(29): 4410–4416, 2010.

Zhang

, Folsom

, Sellers

, Kushi

, Potter

, Better breast cancer survival for postmenopausal women who are less overweight and eat less fat. The Iowa Women’s Health Study, Cancer, 76(2): 275–283, 1995.

Beasley

, Newcomb

, Trentham-Dietz

, Hampton

, Bersch

, Passarelli

, Post-diagnosis dietary factors and survival after invasive breast cancer, Breast Cancer Res Treat, 128(1): 229–236, 2011.

10.

Saxe

, Rock

, Wicha

, Schottenfeld

, Diet and risk for breast cancer recurrence and survival, Breast Cancer Res Treat, 53(3): 241–253, 1999.

11.

Franceschi

, Dal Maso

, Zucchetto

, Talamini

, Prospective Analysis of Case-control studies on Environmental f, health study g. Alcohol consumption and survival after breast cancer; author reply 2–3, Cancer Epidemiol Biomarkers Prevent, 18(3): 1011–1012, 2009, A publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

12.

Barnett

, Shah

, Redman

, Easton

, Ponder

, Pharoah

, Risk factors for the incidence of breast cancer: do they affect survival from the disease?J Clin Oncol, 26(20): 3310–3316, 2008.

13.

Flatt

, Thomson

, Gold

, Natarajan

, Rock

, Al-Delaimy

, Low to moderate alcohol intake is not associated with increased mortality after breast cancer, Cancer Epidemiol Biomarkers Prevent, 19(3): 681–688, 2010, A publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

14.

Holm

, Olsen

, Christensen

, Kroman

, Bidstrup

, Johansen

, Pre-diagnostic alcohol consumption and breast cancer recurrence and mortality: results from a prospective cohort with a wide range of variation in alcohol intake, Int J Cancer, 132(3): 686–694, 2013.

15.

Kwan

, Chen

, Flatt

, Weltzien

, Nechuta

, Poole

, Postdiagnosis alcohol consumption and breast cancer prognosis in the after breast cancer pooling project, Cancer Epidemiol Biomarkers Prevent, 22(1): 32–41, 2013, A publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

16.

Vrieling

, Buck

, Heinz

, Obi

, Benner

, Flesch-Janys

, Pre-diagnostic alcohol consumption and postmenopausal breast cancer survival: a prospective patient cohort study, Breast Cancer Res Treat, 136(1): 195–207, 2012.

17.

Rohan

, Hiller

, McMichael

, Dietary factors and survival from breast cancer, Nutr Cancer, 20(2): 167–177, 1993.

18.

Holmes

, Stampfer

, Colditz

, Rosner

, Hunter

, Willett

, Dietary factors and the survival of women with breast carcinoma, Cancer, 86(5): 826–835, 1999.

19.

McDonald

, Williams

, Dawkins

, Adams-Campbell

, Breast cancer survival in African American women: is alcohol consumption a prognostic indicator?CCC, 13(6): 543–549, 2002.

20.

Vaeth

, Satariano

, Alcohol consumption and breast cancer stage at diagnosis, Alcohol Clin Exp Res, 22(4): 928–934, 1998.

21.

Satariano

, Ragland

, The effect of comorbidity on 3-year survival of women with primary breast cancer, Ann Intern Med, 120(2): 104–110, 1994.

22.

Izano

, Satariano

, Hiatt

, Braithwaite

, The impact of functional limitations on long-term outcomes among African–American and white women with breast cancer: a cohort study, BMJ, 3(10): 2013, e003232.

23.

Izano

, Satariano

, Tammemagi

, Ragland

, Moore

, Allen

, Long-term outcomes among African–American and white women with breast cancer: what is the impact of comorbidity?J Geriatr Oncol, 2014.

24.

Izano

, Satariano

, Hiatt

, Braithwaite

, Smoking and mortality after breast cancer diagnosis: the health and functioning in women study, Cancer Med, 4(2): 315–324, 2015.

25.

Hilton

, Clark

, Changes in American drinking patterns and problems, 1967–1984, J Stud Alcohol, 48(6): 515–522, 1987.

26.

Satariano

, Ragland

, Upper-body strength and breast cancer: a comparison of the effects of age and disease, J Gerontol (A Biol Sci Med Sci), 51(5): 1996, M215-9.

27.

Grambsch

, Therneau

, Proportional hazards tests and diagnostics based on weighted residuals, Biometrika, 81(3): 515–526, 1994.

28.

Harris

, Bergkvist

, Wolk

, Alcohol intake and mortality among women with invasive breast cancer, Br J Cancer, 106(3): 592–595, 2012.

29.

Al-Sader

, Abdul-Jabar

, Allawi

, Haba

, Alcohol and breast cancer: the mechanisms explained, J. Clin Med Res, 1(3): 125–131, 2009.

30.

Purohit

, Can alcohol promote aromatization of androgens to estrogens?Rev Alcohol, 22(3): 123–127, 2000.

31.

Enger

, Ross

, Paganini-Hill

, Longnecker

, Bernstein

, Alcohol consumption and breast cancer oestrogen and progesterone receptor status, Br J Cancer, 79(7–8): 1308–1314, 1999.

32.

Castro

, Delgado de Layno

, Costantini

, Castro

, Cytosolic xanthine oxidoreductase mediated bioactivation of ethanol to acetaldehyde and free radicals in rat breast tissue. Its potential role in alcohol-promoted mammary cancer, Toxicology, 160(1–3): 11–18, 2001.

33.

Bradley

, Badrinath

, Bush

, Boyd-Wickizer

, Anawalt

, Medical risks for women who drink alcohol, J Gen Intern Med, 13(9): 627–639, 1998.

34.

Ely

, Hardy

, Longford

, Wadsworth

, Gender differences in the relationship between alcohol consumption and drink problems are largely accounted for by body water, Alcohol Alcohol, 34(6): 894–902, 1999.

35.

Stryker

, Kaplan

, Stein

, Stampfer

, Sober

, Willett

, The relation of diet, cigarette smoking, and alcohol consumption to plasma beta-carotene and alpha-tocopherol levels, Am J Epidemiol, 127(2): 283–296, 1988.

36.

Wei

, Kim

, Boudreau

, Association of smoking with serum and dietary levels of antioxidants in adults: NHANES III, 1988–1994, Am J Public Health, 91(2): 258–264, 2001.

37.

Simonsson

, Markkula

, Bendahl

, Rose

, Ingvar

, Jernstrom

, Pre- and postoperative alcohol consumption in breast cancer patients: impact on early events, SpringerPlus, 3: 261, 2014.

38.

Opie

, Lecour

, The red wine hypothesis: from concepts to protective signalling molecules, Eur Heart J, 28(14): 1683–1693, 2007.

39.

Frankel

, Kanner

, German

, Parks

, Kinsella

, Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine, Lancet, 341(8843): 454–457, 1993.

40.

Croft

, The chemistry and biological effects of flavonoids and phenolic acids, Ann NY Acad Sci, 854: 435–442, 1998.

Alcohol consumption and mortality after breast cancer diagnosis: The health and functioning in women study

Abstract

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

Introduction

Methods

Study population

Assessment of alcohol consumption

Covariates

Ascertainment of outcomes

Statistical analysis

Results

Mortality from causes other than breast cancer

Breast cancer-specific mortality

Discussion

Ethical considerations

Footnotes

Acknowledgements

Author’s disclosures of potential conflicts of interest

Funding

References