title: Caffeine and Caffeic Acid Inhibit Growth and Modify Estrogen Receptor and Insulin-like Growth Factor I Receptor Levels in Human Breast Cancer.
abstract: OBJECTIVE
  Epidemiologic studies indicate that dietary factors, such as coffee, may influence breast cancer and modulate hormone receptor status. The purpose of this translational study was to investigate how coffee may affect breast cancer growth in relation to estrogen receptor-α (ER) status.
  
  
  METHODS
  The influence of coffee consumption on patient and tumor characteristics and disease-free survival was assessed in a population-based cohort of 1,090 patients with invasive primary breast cancer in Sweden. Cellular and molecular effects by the coffee constituents caffeine and caffeic acid were evaluated in ER(+) (MCF-7) and ER(-) (MDA-MB-231) breast cancer cells.
  
  
  RESULTS
  Moderate (2-4 cups/day) to high (≥5 cups/day) coffee intake was associated with smaller invasive primary tumors (Ptrend = 0.013) and lower proportion of ER(+) tumors (Ptrend = 0.018), compared with patients with low consumption (≤1 cup/day). Moderate to high consumption was associated with lower risk for breast cancer events in tamoxifen-treated patients with ER(+) tumors (adjusted HR, 0.51; 95% confidence interval, 0.26-0.97). Caffeine and caffeic acid suppressed the growth of ER(+) (P ≤ 0.01) and ER(-) (P ≤ 0.03) cells. Caffeine significantly reduced ER and cyclin D1 abundance in ER(+) cells. Caffeine also reduced the insulin-like growth factor-I receptor (IGFIR) and pAkt levels in both ER(+) and ER(-) cells. Together, these effects resulted in impaired cell-cycle progression and enhanced cell death.
  
  
  CONCLUSIONS
  The clinical and experimental findings demonstrate various anticancer properties of caffeine and caffeic acid against both ER(+) and ER(-) breast cancer that may sensitize tumor cells to tamoxifen and reduce breast cancer growth.
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden. ann.rosendahl@med.lu.se.
authors.forename: Ann H
authors.initials: AH
authors.lastname: Rosendahl
authors.affiliation: University of Bristol, School of Clinical Sciences, IGFs and Metabolic Endocrinology Group, Southmead Hospital, Bristol, United Kingdom.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Perks
authors.affiliation: University of Bristol, School of Clinical Sciences, IGFs and Metabolic Endocrinology Group, Southmead Hospital, Bristol, United Kingdom.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Markkula
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Simonsson
authors.affiliation: Lund University, CREATE Health and Department of Immunotechnology, Medicon Village, Lund, Sweden.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rose
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Surgery, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.affiliation: University of Bristol, School of Clinical Sciences, IGFs and Metabolic Endocrinology Group, Southmead Hospital, Bristol, United Kingdom.
authors.forename: Jeff M P
authors.initials: JM
authors.lastname: Holly
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Jernström
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D040503:Coffea; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D012307:Risk Factors; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D002109:Caffeic Acids; D011960:Receptors, Estrogen; D002110:Caffeine; D017526:Receptor, IGF Type 1; C040048:caffeic acid