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Coffee prevents early events in tamoxifen-treated breast cancer patients and modulates hormone receptor status

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Abstract

Purpose

Whether coffee modulates response to endocrine therapy in breast cancer patients is currently unknown. The CYP1A2 and CYP2C8 enzymes contribute to tamoxifen and caffeine metabolism. The purpose was to investigate the impact of coffee consumption on tumor characteristics and risk for early events in relation to breast cancer treatment and CYP1A2 and CYP2C8 genotypes.

Methods

Questionnaires regarding lifestyle were completed preoperatively by 634 patients in southern Sweden. CYP1A2*1F and CYP2C8*3 were genotyped. Clinical data and tumor characteristics were obtained from patients’ charts, population registries, and pathology reports. Coffee consumption was categorized as low (0–1 cups/day), moderate (2–4 cups/day), or high (5+ cups/day).

Results

The proportion of estrogen receptor negative (ER–) tumors increased with increasing coffee consumption (p trend = 0.042). Moderate to high consumption was associated with lower frequency of discordant receptor status (ER + PgR–) OR 0.38 (0.23–0.63) compared to low consumption. Median follow-up time was 4.92 (IQR 3.01–6.42) years. Tamoxifen-treated patients with ER+ tumors (n = 310) who consumed two or more cups/day had significantly decreased risk for early events compared to patients with low consumption, adjusted HR 0.40 (0.19–0.83). Low consumption combined with at least one CYP1A2*1F C-allele (n = 35) or CYP2C8*3 (n = 13) was associated with a high risk for early events in tamoxifen-treated patients compared to other tamoxifen-treated patients, adjusted HRs 3.49 (1.54–7.91) and 6.15 (2.46–15.36), respectively.

Conclusion

Moderate to high coffee consumption was associated with significantly decreased risk for early events in tamoxifen-treated patients and modified hormone receptor status. If confirmed, new recommendations regarding coffee consumption during tamoxifen treatment may be warranted.

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References

  1. The National Board of Health and Welfare (2011) Cancer incidence in Sweden 2010. http://www.socialstyrelsen.se/Lists/Artikelkatalog/Attachments/18530/2011-12-15.pdf

  2. Fernö M, Borg Å, Johansson U, Norgren A, Olsson H, Ryden S, Sellberg G (1990) Estrogen and progesterone receptor analyses in more than 4,000 human breast cancer samples. A study with special reference to age at diagnosis and stability of analyses. Southern Swedish Breast Cancer Study Group. Acta Oncol 29(2):129–135

    Article  PubMed  Google Scholar 

  3. Larsson SC, Bergkvist L, Wolk A (2009) Coffee and black tea consumption and risk of breast cancer by estrogen and progesterone receptor status in a Swedish cohort. Cancer Causes Control 20(10):2039–2044. doi:10.1007/s10552-009-9396-x

    Article  PubMed  Google Scholar 

  4. Conzen SD (2008) Minireview: nuclear receptors and breast cancer. Mol Endocrinol 22(10):2215–2228. doi:10.1210/me.2007-0421

    Article  PubMed  CAS  Google Scholar 

  5. Osborne CK, Schiff R (2011) Mechanisms of endocrine resistance in breast cancer. Annu Rev Med 62:233–247. doi:10.1146/annurev-med-070909-182917

    Article  PubMed  CAS  Google Scholar 

  6. Li J, Seibold P, Chang-Claude J, Flesch-Janys D, Liu J, Czene K, Humphreys K, Hall P (2011) Coffee consumption modifies risk of estrogen-receptor negative breast cancer. Breast Cancer Res 13(3):R49. doi:10.1186/bcr2879

    Article  PubMed  Google Scholar 

  7. The European Coffee Federation (2010) The European coffee report, vol 2011. The European Coffee Federation. http://www.scribd.com/doc/45025346/European-Coffee-Report-2009

  8. Allred KF, Yackley KM, Vanamala J, Allred CD (2009) Trigonelline is a novel phytoestrogen in coffee beans. J Nutr 139(10):1833–1838. doi:10.3945/jn.109.108001

    Article  PubMed  CAS  Google Scholar 

  9. Michels KB, Holmberg L, Bergkvist L, Wolk A (2002) Coffee, tea, and caffeine consumption and breast cancer incidence in a cohort of Swedish women. Ann Epidemiol 12(1):21–26

    Article  PubMed  Google Scholar 

  10. Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R (2012) Association of coffee drinking with total and cause-specific mortality. N Engl J Med 366(20):1891–1904. doi:10.1056/NEJMoa1112010

    Article  PubMed  CAS  Google Scholar 

  11. Svenska bröstcancergruppen (2011) Nationella riktlinjer 2011, vårdprogram.. http://www.swebcg.se/Files/Docs/Nationella_riktlinjer110131.pdf. Accessed 20110512 2011

  12. Jordan VC, Koerner S (1975) Tamoxifen (ICI 46,474) and the human carcinoma 8S oestrogen receptor. Eur J Cancer 11(3):205–206

    PubMed  CAS  Google Scholar 

  13. Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97(1):30–39. doi:10.1093/jnci/dji005

    Article  PubMed  CAS  Google Scholar 

  14. Dunn BK, Greene MH, Kelley JM, Costantino JP, Clifford RJ, Hu Y, Tang G, Kazerouni N, Rosenberg PS, Meerzaman DM, Buetow KH (2010) Novel pathway analysis of genomic polymorphism-cancer risk interaction in the breast cancer prevention trial. Int J Mol Epidemiol Genet 1(4):332–349

    PubMed  CAS  Google Scholar 

  15. Chen J, Halls SC, Alfaro JF, Zhou Z, Hu M (2004) Potential beneficial metabolic interactions between tamoxifen and isoflavones via cytochrome P450-mediated pathways in female rat liver microsomes. Pharm Res 21(11):2095–2104

    Article  PubMed  CAS  Google Scholar 

  16. Andersson H, Helmestam M, Zebrowska A, Olovsson M, Brittebo E (2010) Tamoxifen-induced adduct formation and cell stress in human endometrial glands. Drug Metab Dispos 38(1):200–207. doi:10.1124/dmd.109.029488

    Article  PubMed  CAS  Google Scholar 

  17. Kot M, Daniel WA (2008) The relative contribution of human cytochrome P450 isoforms to the four caffeine oxidation pathways: an in vitro comparative study with cDNA-expressed P450 s including CYP2C isoforms. Biochem Pharmacol 76(4):543–551. doi:10.1016/j.bcp.2008.05.025

    Article  PubMed  CAS  Google Scholar 

  18. Bågeman E, Ingvar C, Rose C, Jernström H (2008) Coffee consumption and CYP1A2*1F genotype modify age at breast cancer diagnosis and estrogen receptor status. Cancer Epidemiol Biomarkers Prev 17(4):895–901. doi:10.1158/1055-9965.EPI-07-0555

    Article  PubMed  Google Scholar 

  19. Sachse C, Brockmoller J, Bauer S, Roots I (1999) Functional significance of a C–>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 47(4):445–449

    Article  PubMed  CAS  Google Scholar 

  20. Djordjevic N, Ghotbi R, Jankovic S, Aklillu E (2010) Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 -163C > A polymorphism. Eur J Clin Pharmacol 66(7):697–703. doi:10.1007/s00228-010-0823-4

    Article  PubMed  CAS  Google Scholar 

  21. Jernström H, Bågeman E, Rose C, Jönsson PE, Ingvar C (2009) CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients. Br J Cancer 101(11):1817–1823. doi:10.1038/sj.bjc.6605428

    Article  PubMed  Google Scholar 

  22. Ringberg A, Bågeman E, Rose C, Ingvar C, Jernström H (2006) Of cup and bra size: reply to a prospective study of breast size and premenopausal breast cancer incidence. Int J Cancer 119(9):2242–2243. Author reply 2244. doi:10.1002/ijc.22104

    Google Scholar 

  23. Osborne CK, Yochmowitz MG, Knight WA 3rd, McGuire WL (1980) The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 46(12 Suppl):2884–2888

    Article  PubMed  CAS  Google Scholar 

  24. Cui X, Schiff R, Arpino G, Osborne CK, Lee AV (2005) Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol 23(30):7721–7735. doi:10.1200/JCO.2005.09.004

    Article  PubMed  CAS  Google Scholar 

  25. Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM (2003) Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol 21(10):1973–1979. doi:10.1200/JCO.2003.09.099

    Article  PubMed  CAS  Google Scholar 

  26. Hashimoto T, He Z, Ma WY, Schmid PC, Bode AM, Yang CS, Dong Z (2004) Caffeine inhibits cell proliferation by G0/G1 phase arrest in JB6 cells. Cancer Res 64(9):3344–3349

    Article  PubMed  CAS  Google Scholar 

  27. Cui X, Zhang P, Deng W, Oesterreich S, Lu Y, Mills GB, Lee AV (2003) Insulin-like growth factor-I inhibits progesterone receptor expression in breast cancer cells via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway: progesterone receptor as a potential indicator of growth factor activity in breast cancer. Mol Endocrinol 17(4):575–588. doi:10.1210/me.2002-0318

    Article  PubMed  CAS  Google Scholar 

  28. Divekar SD, Storchan GB, Sperle K, Veselik DJ, Johnson E, Dakshanamurthy S, Lajiminmuhip YN, Nakles RE, Huang L, Martin MB (2011) The role of calcium in the activation of estrogen receptor-alpha. Cancer Res 71(5):1658–1668. doi:10.1158/0008-5472.CAN-10-1899

    Article  PubMed  CAS  Google Scholar 

  29. Caldarella A, Crocetti E, Bianchi S, Vezzosi V, Urso C, Biancalani M, Zappa M (2011) Female breast cancer status according to ER, PR and HER2 expression: a population based analysis. Pathol Oncol Res. doi:10.1007/s12253-011-9381-z

    Google Scholar 

  30. Jernström H, Klug TL, Sepkovic DW, Bradlow HL, Narod SA (2003) Predictors of the plasma ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone among pre-menopausal, nulliparous women from four ethnic groups. Carcinogenesis 24(5):991–1005

    Article  PubMed  Google Scholar 

  31. Bradlow HL, Jernström H, Sepkovic DW, Klug TL, Narod SA (2006) Comparison of plasma and urinary levels of 2-hydroxyestrogen and 16 alpha-hydroxyestrogen metabolites. Mol Genet Metab 87(2):135–146. doi:10.1016/j.ymgme.2005.08.001

    Article  PubMed  CAS  Google Scholar 

  32. Klug TL, Bågeman E, Ingvar C, Rose C, Jernström H (2006) Moderate coffee and alcohol consumption improves the estrogen metabolite profile in adjuvant treated breast cancer patients: a pilot study comparing pre- and post-operative levels. Mol Genet Metab 89(4):381–389. doi:10.1016/j.ymgme.2006.08.005

    Article  PubMed  CAS  Google Scholar 

  33. Schneider J, Huh MM, Bradlow HL, Fishman J (1984) Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells. J Biol Chem 259(8):4840–4845

    PubMed  CAS  Google Scholar 

  34. Telang NT, Suto A, Wong GY, Osborne MP, Bradlow HL (1992) Induction by estrogen metabolite 16 alpha-hydroxyestrone of genotoxic damage and aberrant proliferation in mouse mammary epithelial cells. J Natl Cancer Inst 84(8):634–638

    Article  PubMed  CAS  Google Scholar 

  35. Thibodeau PA, Bissonnette N, Bedard SK, Hunting D, Paquette B (1998) Induction by estrogens of methotrexate resistance in MCF-7 breast cancer cells. Carcinogenesis 19(9):1545–1552

    Article  PubMed  CAS  Google Scholar 

  36. Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT (2003) Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology 144(8):3382–3398

    Article  PubMed  CAS  Google Scholar 

  37. Berthou F, Flinois JP, Ratanasavanh D, Beaune P, Riche C, Guillouzo A (1991) Evidence for the involvement of several cytochromes P-450 in the first steps of caffeine metabolism by human liver microsomes. Drug Metab Dispos 19(3):561–567

    PubMed  CAS  Google Scholar 

  38. Bahadur N, Leathart JB, Mutch E, Steimel-Crespi D, Dunn SA, Gilissen R, Houdt JV, Hendrickx J, Mannens G, Bohets H, Williams FM, Armstrong M, Crespi CL, Daly AK (2002) CYP2C8 polymorphisms in Caucasians and their relationship with paclitaxel 6alpha-hydroxylase activity in human liver microsomes. Biochem Pharmacol 64(11):1579–1589

    Article  PubMed  CAS  Google Scholar 

  39. Larsson SC, Giovannucci E, Wolk A (2006) Coffee consumption and stomach cancer risk in a cohort of Swedish women. Int J Cancer 119(9):2186–2189. doi:10.1002/ijc.22105

    Article  PubMed  CAS  Google Scholar 

  40. Jernström H, Frenander J, Fernö M, Olsson H (1999) Hormone replacement therapy before breast cancer diagnosis significantly reduces the overall death rate compared with never-use among 984 breast cancer patients. Br J Cancer 80(9):1453–1458. doi:10.1038/sj.bjc.6690543

    Article  PubMed  Google Scholar 

  41. Schuetz F, Diel IJ, Pueschel M, von Holst T, Solomayer EF, Lange S, Sinn P, Bastert G, Sohn C (2007) Reduced incidence of distant metastases and lower mortality in 1072 patients with breast cancer with a history of hormone replacement therapy. Am J Obstet Gynecol 196(4):342 e341–349. doi:10.1016/j.ajog.2006.10.901

    Google Scholar 

  42. Nanda K, Bastian LA, Schulz K (2002) Hormone replacement therapy and the risk of death from breast cancer: a systematic review. Am J Obstet Gynecol 186(2):325–334

    Article  PubMed  CAS  Google Scholar 

  43. Stahlberg C, Lynge E, Andersen ZJ, Keiding N, Ottesen B, Rank F, Hundrup YA, Obel EB, Pedersen AT (2005) Breast cancer incidence, case-fatality and breast cancer mortality in Danish women using hormone replacement therapy–a prospective observational study. Int J Epidemiol 34(4):931–935. doi:10.1093/ije/dyi103

    Article  PubMed  Google Scholar 

  44. Chlebowski RT, Anderson GL, Gass M, Lane DS, Aragaki AK, Kuller LH, Manson JE, Stefanick ML, Ockene J, Sarto GE, Johnson KC, Wactawski-Wende J, Ravdin PM, Schenken R, Hendrix SL, Rajkovic A, Rohan TE, Yasmeen S, Prentice RL (2010) Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 304(15):1684–1692. doi:10.1001/jama.2010.1500

    Article  PubMed  CAS  Google Scholar 

  45. Markkula A, Hietala M, Henningson M, Ingvar C, Rose C, Jernström H (2012) Clinical profiles predict early nonadherence to adjuvant endocrine treatment in a prospective breast cancer cohort. Cancer Prev Res (Phila) 5(5):735–745. doi:10.1158/1940-6207.CAPR-11-0442

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from The Swedish Cancer Society CAN 2011/497, the Swedish Research Council K2012-54X-22027-01-3 (PI H Jernström), the Medical Faculty at Lund University; the Mrs. Berta Kamprad’s Foundation, the Gunnar Nilsson Foundation, the Swedish Breast Cancer Group (BRO), the South Swedish Health Care Region (Region Skåne ALF), Konung Gustaf V:s Jubileumsfond, and Lund Hospital Fund. We thank our research nurses Maj-Britt Hedenblad, Karin Henriksson, Anette Möller, Monika Meszaros, Anette Ahlin Gullers, and Linda Ågren. We thank Sol-Britt Olsson, Nils-Gunnar Lundin, and Kristina Lövgren for taking care of blood samples and Erika Bågeman for taking care of blood samples and sequencing of CYP1A2*1F for the previous project. We thank Eric Dryver for proofreading.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Oncology, Clinical Sciences, Lund, Lund University, Barngatan 2B, 22185, Lund, Sweden

    Maria Simonsson, Viktoria Söderlind, Maria Henningson, Maria Hjertberg & Helena Jernström

  2. Sahlgrenska University Hospital, Gothenburg, Sweden

    Maria Henningson

  3. Vrinnevi Hospital, Norrköping, Sweden

    Maria Hjertberg

  4. Division of Cancer and Hematology, Skane, Sweden

    Carsten Rose

  5. Department of Surgery, Clinical Sciences, Lund, Lund, Sweden

    Christian Ingvar

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  1. Maria Simonsson
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Correspondence to Helena Jernström.

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Simonsson, M., Söderlind, V., Henningson, M. et al. Coffee prevents early events in tamoxifen-treated breast cancer patients and modulates hormone receptor status. Cancer Causes Control 24, 929–940 (2013). https://doi.org/10.1007/s10552-013-0169-1

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