Abstract 6470: Coffee and tea consumption, coffee-related metabolites, and breast cancer risk in US Women
Authors: Romanos-Nanclares Andrea , Zeleznik Oana A. , Song Mingyang , Willett Walter C. , Tamimi Rulla M. , Chen Wendy Y. , Holmes Michelle D. , Kang Jae Hee , Eliassen A. Heather 
Published: June 2023

Abstract
Background: Coffee intake may protect against breast cancer; however, previous studies have been inconsistent and potential underlying mechanisms remain unclear. We aimed to 1) examine the association between total coffee, tea, and caffeine intake and breast cancer risk and 2) identify plasma metabolites associated with coffee intake and examine these metabolites in relation to breast cancer risk.
Methods: Data on breast cancer risk factors were collected from questionnaires administered biennially and at the time of blood collections (Nurses’ Health study, NHS, distant collection: 1989-1990, recent collection: 2000-2002; NHSII, 1996-1999). We evaluated the association between total coffee (caffeinated and decaffeinated), tea consumption and caffeine intake and breast cancer risk in the full cohort using Cox regression models. Leveraging dietary and metabolomic data, we identified and validated plasma metabolites associated with coffee intake in 2,033 women from the NHSII breast cancer sub-study. We then evaluated the prospective association of all prior (PMID: 32788283) and new coffee-related metabolites with breast cancer risk in a nested case-control study using conditional logistic regression models.
Results: We documented 10,060 cases of invasive breast cancer during 3,901,211 person-years of follow-up. In pooled, multivariable-adjusted models, compared to never consumers (0 cups/d), women consuming ≥6 cups/d of total coffee were at lower risk of invasive breast cancer (HR, 0.91; 95% CI, 0.82, 1.00; P-trend&lt;0.01). Stratified analysis showed a significant effect modification by BMI (P-interaction=0.03). Compared to never consumers, drinking ≥6 cups of coffee per day was inversely associated with risk of invasive breast cancer among lean women (HR, 0.83; 95% CI, 0.72, 0.97) but not among overweight or obese women. Moreover, a lower risk of ER-negative breast cancer was observed with total coffee (HR ≥6 cups/d vs. 0 cups/day 0.75; 95% CI, 0.59, 0.95; P-trend=0.01) and decaffeinated coffee consumption (HR ≥4 cups/d vs. o cups/day 0.66; 95% CI, 0.45, 0.95; P-trend=0.01). Among the 31 studied metabolites, no single metabolite was associated with breast cancer risk. Associations were generally consistent between ER-positive and ER-negative breast cancer, although trigonelline seemed to be suggestively stronger for ER-negative (OR, 95% CI, 0.87, 0.75-1.01; P-value=0.061). Furthermore, 1,7-dimethyluric acid, some cholesterol esters (C18:1 CE, C18:2 CE and C20:4 CE) and trigonelline, all positively associated with coffee, were indicative of an inverse association with breast cancer risk among lean women.
Conclusions: Coffee consumption was associated with lower breast cancer risk, particularly among lean women and ER-negative breast cancer. Some metabolites that might explain some of the observed inverse associations. Nonetheless, these results merit further exploration.
Citation Format: Andrea Romanos-Nanclares, Oana A. Zeleznik, Mingyang Song, Walter C. Willett, Rulla M. Tamimi, Wendy Y. Chen, Michelle D. Holmes, Jae Hee Kang, A. Heather Eliassen. Coffee and tea consumption, coffee-related metabolites, and breast cancer risk in US Women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6470.