PURPOSE: Epidemiological 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 impact on breast cancer growth in relation to estrogen receptor-α (ER) status. EXPERIMENTAL DESIGN: The influence of coffee consumption on patient- and tumor characteristics, and disease-free survival was assessed in a population-based cohort of 1090 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 were associated with smaller invasive primary tumors (Ptrend=0.013) and lower proportion of ER+ tumors (Ptrend=0.018), compared to 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% CI 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 (IGF-IR) and pAkt levels in both ER+ and ER- cells. Together these effects resulted in impaired cell cycle progression and enhanced cell death. CONCLUSION: 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.
- Received July 8, 2014.
- Revision received December 9, 2014.
- Accepted February 2, 2015.
- Copyright © 2015, American Association for Cancer Research.