• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Arch Intern Med. Author manuscript; available in PMC Oct 13, 2009.
Published in final edited form as:
PMCID: PMC2574428
NIHMSID: NIHMS47479

Caffeine Consumption and Risk of Breast Cancer in a Large Prospective Cohort of Women

Ken Ishitani, MD, PhD, Jennifer Lin, PhD, JoAnn E. Manson, MD, DrPH, Julie E. Buring, ScD, and Shumin M. Zhang, MD, ScD

Abstract

Background

Prospective data relating caffeine consumption to breast cancer risk are limited. We evaluated the association among women enrolled in a completed cancer prevention trial.

Methods

Detailed dietary information was obtained at baseline (1992–1995) among 38,432 women aged ≥45 years and free of cancer. During an average of 10 years of follow-up, we identified 1188 invasive breast cancer cases.

Results

Consumption of caffeine and caffeinated beverages and foods was not statistically significantly associated with overall risk of breast cancer. The multivariable relative risks (RRs) of breast cancer were 1.02 (95% confidence interval [CI], 0.84–1.22) for caffeine (top vs. bottom quintile), 1.08 (95% CI, 0.89–1.30) for coffee (≥4 cups/day vs. almost never), and 1.03 (95% CI, 0.85–1.25) for tea (≥2 cups/day vs. almost never). However, among women with benign breast disease, a borderline significant positive association with breast cancer risk was observed for the highest quintile of caffeine (RR = 1.32; 95% CI, 0.99–1.76) and for the highest category of coffee (≥4 cups/day) (RR = 1.35; 95% CI, 1.01–1.80); tests for interaction were marginally significant. Caffeine consumption was also significantly positively associated with risk of developing ER−PR−breast cancer (RR = 1.68; 95% CI, 1.01–2.81) and breast tumors of >2 cm in size (RR = 1.79; 95% CI, 1.18–2.72).

Conclusions

Data show no overall association between caffeine consumption and breast cancer risk. The possibility of an increased risk among women with benign breast disease or for tumors that are ER−PR− or greater than 2 cm in size warrants further study.

Caffeine (1,3,7-trimethylxanthine), a natural purine alkaloid, is probably the most frequently consumed drug in the world.1, 2 Common beverages (coffee, tea, and soft drinks), cocoa or chocolate-containing food products, and certain medications, including headache or pain remedies, and over-the-counter stimulants, are important sources of caffeine.1, 3 In North America, coffee (60–75%) and tea (15–30%) are the primary sources of caffeine in the adult diet.1

Caffeine was hypothesized to increase risk of breast cancer after a report that women with benign breast disease experienced relief from symptoms after elimination of caffeine from their diet,2, 4 because benign breast disease, particularly atypical hyperplasia, is a marker of increased breast cancer risk.5 However, clinical studies have yielded inconsistent results for the effect on symptoms of benign breast disease when caffeine is eliminated or reduced or for the effect of caffeine on the development of benign breast disease.2, 6

Most case-control investigations reported no association between caffeine and/or caffeinated beverages and foods and breast cancer risk,717 but several case-control studies found either an inverse association1820 or a weak positive association.19, 2123 In three case-control studies that have evaluated the association according to menopausal status, two studies observed either a positive association or an inverse association only among premenopausal women,23, 24 and another study found an inverse association for coffee only among postmenopausal women and no association for tea regardless of menopausal status.25 Data from prospective studies, which are less prone to methodological bias, are limited and in general do not support an overall association,2633 except that two studies showed a nonsignificant positive association for black tea34, 35 and one study found a significant inverse association only in postmenopausal women.33 In a few studies that have examined the association according to history of benign breast disease, no significant association was observed among women with benign breast disease.15, 18, 27 A Norwegian cohort reported that coffee reduced risk in lean women, whereas it increased risk in relatively overweight women.31 However, in three other large cohorts,27, 30, 33 and a large population-based case-control study,15 no association was observed in any stratum of body mass index.

Breast cancer consists of diverse subtypes with different risk factors and clinical responsiveness to treatments.36 However, only a few studies have evaluated the association according to hormone receptor status of breast tumors.27, 33 To our knowledge, no previous studies have evaluated the association by tumor size, lymph node metastasis, and tumor differentiation, which reflect the stage of the carcinogenic process. With large numbers of cases and detailed information on tumor characteristics, we conducted a comprehensive analysis in the Women’s Health Study, a large prospective cohort.

METHODS

STUDY COHORT

The Women’s Health Study was established in 1992 when 39,876 female US health professionals (registered nurses, 75%) aged 45 years or older and free of cancer and cardiovascular disease at baseline were enrolled in a randomized trial of low-dose aspirin and vitamin E for the primary prevention of cancer and cardiovascular disease.37, 38 All participants completed a baseline questionnaire inquiring about their medical history and lifestyle factors. As of the end of the trial, March 31, 2004, the average duration of follow-up was 10 years, and follow-up rates for morbidity and mortality were 97.2% and 99.4%, respectively.37, 38 The current analysis was restricted to 38,432 women after the exclusion of 1444 women who did not provide information on beverages and diet, had implausible total energy intakes (<600 kcal/day or >3500 kcal/day), left >70 food items blank, or had pre-randomization cancers that were reported after randomization and confirmed by medical record review.

ASSESSMENT OF CAFFEINE CONSUMPTION

At baseline, 39,310 (98.6 %) women in the Women’s Health Study also completed a 131-item food frequency questionnaire, a format that has been used and validated in the Nurses’ Health Study.3941 The questionnaire assessed average consumption over the past year of a specific amount of foods, including coffee, decaffeinated coffee, tea, caffeinated cola, decaffeinated cola, low-calorie caffeinated cola, low-calorie decaffeinated cola, and chocolate, and allowed nine responses, ranging from “never” to “six or more times per day.” Intakes of nutrients and caffeine consumption were calculated using the US Department of Agriculture food composition data42 and supplemented by food manufactures. In these calculations, we assumed the content of caffeine was 137 mg per cup of coffee, 47 mg per cup of tea, 46 mg per can or bottle of cola beverage, and 7 mg per serving of chocolate candy.43 Validation studies in a similar cohort (Nurses’ Health Study) revealed high correlations between self-reported intake of coffee and other caffeinated beverages assessed by the food frequency questionnaire and by 4 weeks of diet records (r = .78 for coffee; r = .93 for tea; and r = .85 for caffeinated sodas).39 Coffee was the primary source of caffeine intake at baseline (81%), with fewer contributions by tea (10%), low-calorie caffeinated cola (6%), caffeinated cola (1%), chocolate (0.3%), and other foods (1.7%).

ASCERTAINMENT OF BREAST CANCER CASES

The primary endpoint for this analysis was invasive breast cancer, which was initially identified by self-report from the yearly follow-up questionnaires and then confirmed by medical record review. Deaths of participants were identified through reports from family members, postal authorities, and a search of the National Death Index. Medical records and other relevant information were sought and reviewed by an Endpoints Committee consisting of physicians for the confirmation of medical diagnoses. Medical record review confirmed 98% of self-reported breast cancer cases in the Women’s Health Study.44 During an average of 10 years of follow-up, we ascertained 1188 confirmed cases of invasive breast cancer. We also extracted detailed information on breast tumor characteristics at diagnosis from medical records, including estrogen receptor (ER) and progesterone receptor (ER) status (ER+PR+, n = 803 [67.6%]; ER+PR−, n = 125 [10.5%]; ER−PR+, n = 23 [1.9%]; ER−PR−, n = 166 [14.0%]; and unknown, n = 71 [6.0%]), tumor size (≤2 cm, n = 863 [72.6%]; >2 cm, n = 274 [23.1%]; any size with direct extension to chest wall or skin, n = 5 [0.4%]; and unknown, n = 46 [3.9%]), lymph node metastasis (absent, n = 839 [70.6%]; present, n = 284 [23.9%]; and unknown, n = 65 [5.5%]), and histologic grading and differentiation (well, n = 264 cases [22.2%]; moderately, n = 488 [41.1%]; poorly, n = 277 [23.3%]; and unknown, n = 159 [13.4%]). Tumor ER and PR status was determined by the laboratories affiliated with hospitals where breast cancer cases were diagnosed.

STATISTICAL ANALYSIS

We first compared mean values or proportions of baseline risk factors for breast cancer according to the categories of coffee consumption, the primary source of caffeine, to evaluate potential confounding by these variables.

Person-years were calculated for each participant, ranging from the date of randomization to the date of confirmed cancer diagnosis, death, or March 31, 2004, whichever occurred first. Cox proportional hazards regression models were used to calculate the relative risks (RRs) and 95% confidence intervals (CIs).45 We estimated the RRs according to quintiles of caffeine consumption and categories of caffeinated beverages and foods with adjustment for age (in years) and randomized treatment assignment (aspirin vs. placebo, vitamin E vs. placebo). We also conducted a multivariable analysis that additionally adjusted for known or potential risk factors for breast cancer at baseline, including alcohol consumption (none, >0–<10, ≥10–<15, ≥15–<30, or ≥30 g/day), body mass index (<23, ≥23–<25, ≥25–<27, ≥27–<30, or ≥30 kg/m2), family history of breast cancer in a first-degree relative (yes or no), history of hysterectomy (yes or no), bilateral oophorectomy (yes or no), smoking status (never, past, or current), history of benign breast disease (yes or no), age at menarche (≤11, 12, 13, 14 or ≥15 years), parity (0,1–2, 3–4, 5 or ≥6), age at first birth (≤24, 25–29, or ≥30 years), physical activity (kcal/week, in quartiles), total energy intake (kcal/day, in quintiles), multivitamin use (never, past, or current), age at menopause (<45, 45–49, 50–54, 55–59, or ≥60 years), menopausal status (premenopausal, postmenopausal, or uncertain/unknown), and postmenopausal hormone use (never, past, current <5 years, or current ≥5 years). We also conducted analyses excluding incident cases of breast cancer diagnosed within the first two years of follow-up with additional adjustment for mammography screening that was asked on the 12-month questionnaire, or stratifying by menopausal status (pre- or postmenopausal women), history of benign breast disease (yes or no), body mass index (<25 kg/m2 or ≥25 kg/m2), and postmenopausal hormone use (never or current). Tests for multiplicative interaction were performed by log likelihood ratio tests comparing the models with or without interaction terms.

We also performed an analysis according to combined ER and PR status (ER+PR+, ER+PR−, ER−PR−), tumor size (≤2 and >2 cm), lymph node metastasis (with and without metastasis), and histologic grading and differentiation (well, moderately, and poorly differentiated). All statistical tests were two-sided.

RESULTS

In this population, median and 90th percentile values of caffeine intake at baseline were 283.4 mg/day and 658.2 mg/day, respectively. At baseline, 9262 (24.1%) women never drank coffee, 4996 (13.0%) drank less than 1 cup per day, 5448 (14.2%) drank 1 cup per day, 12623 (32.8%) drank 2 to 3 cups per day, 5900 (15.4%) drank at least 4 cups per day, and 203 (0.5%) had missing information on coffee intake (Table 1).

Table 1
Age-standardized baseline characteristics* by coffee consumption in the Women’s Health Study

Table 1 presents the distributions of baseline risk factors for breast cancer according to the frequency of coffee consumption. Women who drank more cups of coffee were more likely to be leaner, less physically active, postmenopausal, current smokers, and have larger number of births. However, they were less likely to experience late age at menarche, late age at first birth, take postmenopausal hormones, have a history of hysterectomy, bilateral oophorectomy, or benign breast disease, and undergo mammography screening. They also tended to consume more caffeine, alcohol, and total energy, but were less likely to consume tea, decaffeinated coffee, decaffeinated cola with sugar, or low-calorie decaffeinated cola. Age, age at menopause, family history of breast cancer, or consumption of caffeinated cola with sugar, low-calorie caffeinated cola, and chocolate did not appear to differ substantially according to coffee consumption.

Intakes of caffeine, coffee, tea, caffeinated cola, low-calorie caffeinated cola, chocolate, decaffeinated coffee, decaffeinated cola, and low-calorie decaffeinated cola were not statistically significantly associated with overall risk of breast cancer in the models adjusted for age and randomized treatment assignment (Table 2). Additional adjustment for risk factors for breast cancer did not materially change the results; the multivariable RR comparing the highest to the lowest quintile of caffeine consumption was 1.02 (95% CI, 0.84–1.22). Compared with almost never users, the multivariable RRs were 1.08 (95% CI, 0.89–1.30) for coffee (≥4 cups/day), 1.03 (95% CI, 0.85–1.25) for tea (≥2 cups/day), 1.17 (95% CI, 0.87–1.57) for caffeinated cola (≥1 can or bottle/day), 0.88 (95% CI, 0.68–1.13) for low-calorie caffeinated cola (≥2 cans or bottles/day), and 0.97 (95% CI, 0.78–1.20) for chocolate (>1 bar or packet/week). The results did not appreciably change after excluding breast cancer cases diagnosed within the first two years of follow-up with additional adjustment for mammography screening that was asked on the 12-month questionnaire; the multivariable RRs were 1.02 (95% CI, 0.83–1.25) for caffeine (top vs. bottom quintile), 1.04 (95% CI, 0.85–1.28) for coffee (≥4 cups/day vs. almost never), 1.12 (95% CI, 0.92–1.37) for tea (≥2 cups/day vs. almost never), 1.16 (95% CI, 0.84–1.60) for caffeinated cola (≥1 can or bottle/day vs. almost never), 0.92 (95% CI, 0.70–1.20) for low-calorie caffeinated cola (≥2 cans or bottles/day vs. almost never), and 1.01 (95% CI, 0.81–1.27) for chocolate (>1 bar or packet/week vs. almost never).

Table 2
Relative risks (RRs) and 95% confidence intervals (CIs) of breast cancer according to quintiles of caffeine and categories of coffee, tea, decaffeinated coffee, caffeinated beverages, and chocolate

Among women with a history of benign breast disease, a borderline significantly increased risk of breast cancer was seen for the highest quintile of caffeine (multivariable RR = 1.32; 95% CI, 0.99–1.76) and for consumption of ≥4 cups/day of coffee (multivariable RR = 1.35; 95% CI, 1.01–1.80) (Table 3); tests for interaction were marginally significant (P = .05 for caffeine and P = .05 for coffee). The associations between consumption of caffeine, coffee, decaffeinated coffee, and tea and risk of breast cancer did not appear to differ by body mass index (P for interaction = .23 for caffeine) (Table 3), menopausal status (P for interaction = .53 for caffeine) and postmenopausal hormone use (P for interaction = .08 for caffeine) (Table 4). Although decaffeinated coffee consumption was not associated with risk of breast cancer among all postmenopausal women, a significant inverse association for decaffeinated coffee was observed among never users of postmenopausal hormones (multivariable RR = 0.58; 95% CI, 0.36–0.93; P = .02 for trend) (Table 4).

Table 3
Relative risks (RRs) and 95% confidence intervals (CIs) of breast cancer according to quintiles of caffeine and categories of coffee, decaffeinated coffee, and tea, by history of benign breast disease (BBD) and body mass index (BMI)
Table 4
Relative risks (RRs) and 95% confidence intervals (CIs) of breast cancer according to quintiles of caffeine and categories of coffee, decaffeinated coffee, and tea, by menopausal status and postmenopausal hormone use.

Separate analyses according to hormone receptor status revealed a significant positive association between caffeine consumption and risk of developing ER−PR− breast cancer; the multivariable RR was 1.68 (95% CI, 1.01–2.81, P = .02 for trend) (top vs. bottom quintile) (Table 5). In addition, a significant positive association for caffeine consumption was found for developing tumors that were >2 cm in size; the multivariable RR was 1.79 (95% CI, 1.18–2.72, P = .02 for trend) (top vs. bottom quintile) (Table 5). There were no significant associations between caffeine consumption and breast cancer risk according to tumor lymph node metastasis, or tumor histological grading and differentiation (Table 5).

Table 5
Relative risks and 95% confidence intervals (CI) of invasive breast cancer according to quintiles of caffeine consumption, by tumor characteristics

COMMENT

In this large cohort of women, we found that consumption of caffeine and caffeinated beverages and foods was not significantly associated with overall risk of breast cancer. There were also no significant associations according to menopausal status, postmenopausal hormone use, body mass index, tumor lymph node metastasis, and tumor histologic grading and differentiation. However, among women with a history of benign breast disease, we observed a borderline significant positive association between consumption of >486.3 mg/day of caffeine or ≥4 cups/day of coffee (the primary source of caffeine) and breast cancer risk. We also found a significant positive association between caffeine consumption and risk of developing breast tumors that were ER−PR−or >2 cm in size.

Previous findings on the association between caffeine or coffee consumption and breast cancer risk have been inconclusive. An ecological analysis showed a strong inverse association between coffee/tea consumption and breast cancer mortality.46 However, higher caffeine consumption has not been associated with risk of breast cancer in most case-control studies.717 Several case-control studies have found a weak positive association, but there were no clear trends of increased risk with increasing consumption,2123, 47 and a few others have observed an inverse association.1820, 25, 48 A recent meta-analysis of 13 case-control and cohort studies indicate a lower risk of breast cancer associated with higher green tea consumption (the main tea consumed in Asia), but conflicting results for black tea (the main tea consumed in US and Europe) -- black tea consumption was associated with a reduced risk of breast cancer in case-control studies, but a slightly increased risk in cohort studies.49

Lack of overall association between consumption of caffeine, coffee, tea (black tea), decaffeinated coffee, soft drinks, and chocolate and risk of breast cancer observed in the Women’s Health Study is generally consistent with the findings from previous prospective cohort studies in North America and Europe, including the Seventh-Day Adventists cohort,26 the Iowa Women’s Health Study,27, 32 the New York State Cohort,28 a Norwegian cohort,50 the Swedish Mammography Screening Cohort,30 and the Nurses’ Health Study.33 In a French cohort study, consumption of coffee and tea was not associated with risk of breast cancer, however, consumption of herbal tea was significantly associated with a reduced risk of breast cancer.51 A nonsignificant positive association for black tea was also observed in the Netherlands Cohort Study.34 In a Japanese cohort, while coffee and black tea consumption was not associated with breast cancer risk, green tea consumption was nonsignificantly inversely associated with risk.29 In two other Japanese cohorts, coffee and green tea consumption was nonsignificantly inversely associated with risk of breast cancer, but black tea was nonsignificantly positively association with risk of breast cancer.35

The mechanisms by which caffeine may affect breast carcinogenesis are complex and remain unclear. Caffeine has been reported to suppress cell cycle and proliferation and induce apoptosis.52 Caffeine also has been positively associated with blood levels of estrone53 and sex hormone-binding globulin,5355 but negatively associated with plasma free estradiol.55 Caffeine and coffee can both stimulate and suppress the development of mammary tumors, depending on the phases of tumorigenesis (initiation/promotion) when caffeine and coffee are administered in rodents.2, 56 Caffeine is a known antagonist of the adenosine receptor.2, 57 Adenosine, an endogenous bioactive substance, exerts its diverse biologic effects through the activation of specific cell surface adenosine receptor.57 In breast cancer cell lines, high concentrations of adenosine inhibited cell growth and induced cell cycle arrest at G2-M phase, but had no effect on ERα levels,58 suggesting that, through antagonism of adenosine receptor, caffeine might be able to stimulate breast cell proliferation independent of ERα pathway.

In the present investigation, caffeine consumption was associated with increased risk of developing breast cancers negative for both ER and PR or with a size of greater than 2 cm, which have less favorable prognoses. These findings indicate that caffeine consumption may affect breast cancer progression and such effect may be independent of the estrogen pathway. These findings, however, are not in line with the results from the Iowa Women’s Health Study and the Nurses’ Health Study, in which there were no associations between caffeine consumption and risk of breast cancer according to ER and PR status, although the caffeine intake levels were generally similar between the Women’s Health Study and the Iowa Women’s Health Study cohorts.

Consistent with the hypothesis that caffeine may increase the risk of breast cancer among women with benign breast disease,2, 4 we found a significantly increased risk associated with the highest quintile of caffeine and consumption of ≥4 cups/day of coffee among women with a history of benign breast disease. These findings suggest that high caffeine consumption may promote the progression from premalignant breast lesions to breast cancers as most types of invasive breast cancer are thought to arise from certain premalignant lesions such as atypical hyperplasia.5 Of note, the increased risk was only apparent among those with the highest amount of intake, and there was no association in those consuming less than 4 cups/day of coffee. However, such findings are inconsistent with the results from the Iowa Women’s Health Study cohort27 and two large case-control studies,15, 18 in which they have found no positive association between caffeine or coffee intake and breast cancer risk among those with benign breast disease.

A Norwegian cohort reported that coffee consumption was associated with a lower risk of breast cancer in lean women, but an increased risk in overweight women.31 However, we, along with the Iowa Women’s Health Study,27 the Swedish Mammography cohort,30 the Nurses’ Health Study,33 and a large case-control study,15 found no significant association between consumption of caffeine and coffee and breast cancer risk according to categories of body mass index.

The strengths of this study include the prospective design and high follow-up rates, which minimize the possibility that our findings are a result of methodological biases. We also minimized the confounding by other risk factors through controlling for established risk factors for breast cancer comprehensively. Our results are also unlikely to be explained by the potential bias that breast cancer itself (before it was diagnosed) may have affected caffeine consumption because the RRs, after excluding case patients who were diagnosed with breast cancer within the first 2 years after randomization, were similar to those using all case patients. In addition, this study had over 1000 incident breast cancer cases with 38,432 women followed for at least 10 years and detailed information on tumor characteristics, which enabled us to evaluate comprehensively the caffeine-breast cancer association according to tumor characteristics. This study also has limitations. Because we used the information on consumption of caffeine and caffeinated beverages and foods only at baseline, which did not account for changes in caffeine consumption over time, measurement error due to random within-person variation is inevitable. Such misclassification in prospective studies tends to weaken any true associations. In addition, because the number of case patients in some exposure categories and categories of tumor characteristics was relatively modest, we had limited statistical power in some subgroup analyses. Finally, we cannot exclude the possibility that our findings in some subgroups may be a result of chance because a large number of subgroups were evaluated. More studies are needed to refute or confirm the associations that we observed in some subgroups.

In conclusion, the findings from this prospective study suggest that caffeine consumption is not related to overall risk of breast cancer. However, our data suggest that high caffeine consumption may increase risk of breast cancer among women with a history of benign breast disease or of breast tumors that are ER−PR− or >2 cm in size, but these findings may be due to chance and warrant further study.

Acknowledgments

Dr. Zhang had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

The authors thank Eduardo Pereira for his statistical analytic support and Natalya Gomelskaya for her assistance with the manuscript, the entire staff of the Women’s Health Study, and the 39,876 dedicated participants of the Women’s Health Study.

Funding/Support: This study was supported by research grants CA096619, CA47988 and HL43851 from the National Institutes of Health.

References

1. Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M. Effects of caffeine on human health. Food Addit Contam. 2003;20:1–30. [PubMed]
2. Wolfrom D, Welsch CW. Caffeine and the development of normal, benign and carcinomatous human breast tissues: a relationship? J Med. 1990;21:225–50. [PubMed]
3. Dlugosz L, Bracken MB. Reproductive effects of caffeine: a review and theoretical analysis. Epidemiol Rev. 1992;14:83–100. [PubMed]
4. Minton JP, Foecking MK, Webster DJ, Matthews RH. Response of fibrocystic disease to caffeine withdrawal and correlation of cyclic nucleotides with breast disease. Am J Obstet Gynecol. 1979;135:157–8. [PubMed]
5. Arpino G, Laucirica R, Elledge RM. Premalignant and in situ breast disease: biology and clinical implications. Ann Intern Med. 2005;143:446–57. [PubMed]
6. Webb PM, Byrne C, Schnitt SJ, et al. A prospective study of diet and benign breast disease. Cancer Epidemiol Biomarkers Prev. 2004;13:1106–13. [PubMed]
7. Ewertz M, Gill C. Dietary factors and breast-cancer risk in Denmark. Int J Cancer. 1990;46:779–84. [PubMed]
8. Graham S, Hellmann R, Marshall J, et al. Nutritional epidemiology of postmenopausal breast cancer in Western New York. Am J Epidemiol. 1991;134:552–66. [PubMed]
9. Iscovich JM, Iscovich RB, Howe G, Shiboski S, Kaldor JM. A case-control study of diet and breast cancer in Argentina. Int J Cancer. 1989;44:770–6. [PubMed]
10. Katsouyanni K, Trichopoulos D, Boyle P, et al. Diet and breast cancer: a case-control study in Greece. Int J Cancer. 1986;38:815–20. [PubMed]
11. Lee HP, Gourley L, Duffy SW, Esteve J, Lee J, Day NE. Dietary effects on breast-cancer risk in Singapore. Lancet. 1991;337:1197–200. [PubMed]
12. Levi F, La Vecchia C, Gulie C, Negri E. Dietary factors and breast cancer risk in Vaud, Switzerland. Nutr Cancer. 1993;19:327–35. [PubMed]
13. Lubin F, Ron E. Consumption of methylxanthine-containing beverages and the risk of breast cancer. Cancer Lett. 1990;53:81–90. [PubMed]
14. McLaughlin CC, Mahoney MC, Nasca PC, Metzger BB, Baptiste MS, Field NA. Breast cancer and methylxanthine consumption. Cancer Causes Control. 1992;3:175–8. [PubMed]
15. Rosenberg L, Miller DR, Helmrich SP, et al. Breast cancer and the consumption of coffee. Am J Epidemiol. 1985;122:391–9. [PubMed]
16. Schairer C, Brinton LA, Hoover RN. Methylxanthines and breast cancer. Int J Cancer. 1987;40:469–73. [PubMed]
17. Tavani A, Pregnolato A, La Vecchia C, Favero A, Franceschi S. Coffee consumption and the risk of breast cancer. Eur J Cancer Prev. 1998;7:77–82. [PubMed]
18. Le MG. Coffee consumption, benign breast disease, and breast cancer. Am J Epidemiol. 1985;122:721. [PubMed]
19. Lubin F, Ron E, Wax Y, Modan B. Coffee and methylxanthines and breast cancer: a case-control study. J Natl Cancer Inst. 1985;74:569–73. [PubMed]
20. Wu AH, Yu MC, Tseng CC, Hankin J, Pike MC. Green tea and risk of breast cancer in Asian Americans. Int J Cancer. 2003;106:574–9. [PubMed]
21. La Vecchia C, Talamini R, Decarli A, Franceschi S, Parazzini F, Tognoni G. Coffee consumption and the risk of breast cancer. Surgery. 1986;100:477–81. [PubMed]
22. Lawson DH, Jick H, Rothman KJ. Coffee and tea consumption and breast disease. Surgery. 1981;90:801–3. [PubMed]
23. Rohan TE, McMichael AJ. Methylxanthines and breast cancer. Int J Cancer. 1988;41:390–3. [PubMed]
24. Baker JA, Beehler GP, Sawant AC, Jayaprakash V, McCann SE, Moysich KB. Consumption of coffee, but not black tea, is associated with decreased risk of premenopausal breast cancer. J Nutr. 2006;136:166–71. [PubMed]
25. Mannisto S, Pietinen P, Virtanen M, Kataja V, Uusitupa M. Diet and the risk of breast cancer in a case-control study: does the threat of disease have an influence on recall bias? J Clin Epidemiol. 1999;52:429–39. [PubMed]
26. Snowdon DA, Phillips RL. Coffee consumption and risk of fatal cancers. Am J Public Health. 1984;74:820–3. [PMC free article] [PubMed]
27. Folsom AR, McKenzie DR, Bisgard KM, Kushi LH, Sellers TA. No association between caffeine intake and postmenopausal breast cancer incidence in the Iowa Women's Health Study. Am J Epidemiol. 1993;138:380–3. [PubMed]
28. Graham S, Zielezny M, Marshall J, et al. Diet in the epidemiology of postmenopausal breast cancer in the New York State cohort. Am J Epidemiol. 1992;136:1327–37. [PubMed]
29. Key TJ, Sharp GB, Appleby PN, et al. Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan. Br J Cancer. 1999;81:1248–56. [PMC free article] [PubMed]
30. Michels KB, Holmberg L, Bergkvist L, Wolk A. Coffee, tea, and caffeine consumption and breast cancer incidence in a cohort of Swedish women. Ann Epidemiol. 2002;12:21–6. [PubMed]
31. Vatten LJ, Solvoll K, Loken EB. Coffee consumption and the risk of breast cancer. A prospective study of 14,593 Norwegian women. Br J Cancer. 1990;62:267–70. [PMC free article] [PubMed]
32. Zheng W, Doyle TJ, Kushi LH, Sellers TA, Hong CP, Folsom AR. Tea consumption and cancer incidence in a prospective cohort study of postmenopausal women. Am J Epidemiol. 1996;144:175–82. [PubMed]
33. Ganmaa D, Willett WC, Li TY, et al. Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up. Int J Cancer. 2008;122:2071–6. [PubMed]
34. Goldbohm RA, Hertog MG, Brants HA, van Poppel G, van den Brandt PA. Consumption of black tea and cancer risk: a prospective cohort study. J Natl Cancer Inst. 1996;88:93–100. [PubMed]
35. Suzuki Y, Tsubono Y, Nakaya N, Koizumi Y, Tsuji I. Green tea and the risk of breast cancer: pooled analysis of two prospective studies in Japan. Br J Cancer. 2004;90:1361–3. [PMC free article] [PubMed]
36. Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006;295:2492–502. [PubMed]
37. Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005;294:47–55. [PubMed]
38. Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005;294:56–65. [PubMed]
39. Salvini S, Hunter DJ, Sampson L, et al. Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. Int J Epidemiol. 1989;18:858–867. [PubMed]
40. Willett WC, Sampson L, Browne ML, et al. The use of a self-administered questionnaire to assess diet four years in the past. Am J Epidemiol. 1988;127:188–199. [PubMed]
41. Willett WC, Sampson L, Stampfer MJ, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol. 1985;122:51–65. [PubMed]
42. U.S. Department of Agriculture Agricultural Research Service. USDA Nutrient Database for Standard Reference, Release 10: Nutrient Data Laboratory Home Page. 1993. http://www.nal.usda.gov/fnic/foodcomp;
43. Willett WC, Stampfer MJ, Manson JE, et al. Coffee consumption and coronary heart disease in women. A ten-year follow-up. JAMA. 1996;275:458–62. [PubMed]
44. Lee IM, Rexrode KM, Cook NR, Hennekens CH, Burin JE. Physical activity and breast cancer risk: the Women's Health Study (United States) Cancer Causes Control. 2001;12:137–45. [PubMed]
45. Cox DR, McCullagh P. Some aspects of analysis of covariance. Biometrics. 1982;38:541–61. [PubMed]
46. Phelps HM, Phelps CE. Caffeine ingestion and breast cancer. A negative correlation. Cancer. 1988;61:1051–4. [PubMed]
47. Lubin JH, Burns PE, Blot WJ, Ziegler RG, Lees AW, Fraumeni JF., Jr Dietary factors and breast cancer risk. Int J Cancer. 1981;28:685–9. [PubMed]
48. Nkondjock A, Ghadirian P, Kotsopoulos J, et al. Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers. Int J Cancer. 2006;118:103–7. [PubMed]
49. Sun CL, Yuan JM, Koh WP, Yu MC. Green tea, black tea and breast cancer risk: a meta-analysis of epidemiological studies. Carcinogenesis. 2006;27:1310–5. [PubMed]
50. Jacobsen BK, Bjelke E, Kvale G, Heuch I. Coffee drinking, mortality, and cancer incidence: results from a Norwegian prospective study. J Natl Cancer Inst. 1986;76:823–31. [PubMed]
51. Hirvonen T, Mennen LI, de Bree A, et al. Consumption of antioxidant-rich beverages and risk for breast cancer in French women. Ann Epidemiol. 2006;16:503–8. [PubMed]
52. Bode AM, Dong Z. The enigmatic effects of caffeine in cell cycle and cancer. Cancer Lett. 2007;247:26–39. [PMC free article] [PubMed]
53. Ferrini RL, Barrett-Connor E. Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol. 1996;144:642–4. [PubMed]
54. Nagata C, Kabuto M, Shimizu H. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese women. Nutr Cancer. 1998;30:21–4. [PubMed]
55. London S, Willett W, Longcope C, McKinlay S. Alcohol and other dietary factors in relation to serum hormone concentrations in women at climacteric. Am J Clin Nutr. 1991;53:166–171. [PubMed]
56. VanderPloeg LC, Welsch CW. Inhibition by caffeine of ovarian hormone-induced mammary gland tumorigenesis in female GR mice. Cancer Lett. 1991;56:245–50. [PubMed]
57. Jacobson KA, Gao ZG. Adenosine receptors as therapeutic targets. Nat Rev Drug Discov. 2006;5:247–64. [PMC free article] [PubMed]
58. Lu J, Pierron A, Ravid K. An adenosine analogue, IB-MECA, down-regulates estrogen receptor alpha and suppresses human breast cancer cell proliferation. Cancer Res. 2003;63:6413–23. [PubMed]
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...