Abstract A23: Association of gut microbiome diversity with obesity and breast density in postmenopausal women
Authors: Yaghjyan Lusine , Wang Xuefeng , Ukhanova Maria , Martinez Yessica , Rich Shannan , Mai Volker , Egan Kathleen 
Published: December 2020

Abstract
Purpose: The plausible roles of the gut microbiome (GM) in obesity as well as breast cancer have been discussed in recent reviews. The associations of GM with mammographic breast density (BD), a well-established strong breast cancer risk factor, also associated with body mass index (BMI), are poorly studied. We examined GM profiles in relation to BD and BMI in a sample of healthy postmenopausal women.
Methods: Women were recruited in mammography clinics at Moffitt Cancer Center and via recruitment announcements at the University of Florida. Eligible women were postmenopausal, had a BMI ≤35 kg/m2, and had not taken oral/IV antibiotics within 30 days and/or more than two separate antibiotic regimens within the previous three months. All women provided a fecal sample and comprehensive information on breast cancer risk factors including body weight and height. Mammographic BD was available for 69 women recruited at Moffitt and was classified according to the American College of Radiology’s BI-RADS BD classification system. For this analysis, BD was dichotomized as low (BI-RADS I or II) or high (BI-RADS III and IV). DNA was isolated from fecal samples and the V1-V2 hypervariable regions of 16S rRNA amplified using barcoded primers for sequencing on the Illumina MiSeq platform. Chao1, Inverse Simpson, and Shannon indices were used to classify within sample diversity. The two-sample Wilcoxon test was used to examine associations of GM with BD and BMI. Associations were also examined according to the ratio of the two main phyla in the human GM (Firmicutes and Bacteroidetes; F/B ratio) that has been linked to obesity in previous studies.
Results: Among 69 women with BD data, 39 had low BD and 30 had high BD. BMI was inversely associated with BD (mean BMI=23.8 in women with high BD and BMI=28.0 in women with low BD, p=1.07 × 10-5). The F/B ratio was not associated with BMI (median F/B ratio=0.90, 0.84, and 0.96 for normal weight, overweight, and obesity, respectively, p=0.57). Similar levels of diversity were found across weight groups according to the Shannon (4.05, 3.97, and 3.96, respectively, p=0.83); inverse Simpson (20.6, 20.1, and 19.3, respectively, p=0.97); and chao1 (433, 441, and 419, respectively, p=0.31) indices. F/B ratio and microbiota diversity were both suggestively greater in women with high vs. low BD (median F/B ratio=1.15 for high and 0.94 for low BD, p=0.35; Shannon index: 4.24 for high and 4.15 for low BD, p=0.14; inverse Simpson= 25.3 for high and 21.0 for low BD, p=0.15; chao1= 519 for high and 429 for low BD, p=0.17). Highest levels of alpha diversity were observed in women who had both high BD and low BMI. Taxonomic families that distinguished women with high vs. low BD included Ruminococcaceae, Mogibacteriaceae, Bacteroidaceae, Lachnospiraceae, Christensenellaceae, and Coriobacteriaceae.
Conclusion: Results suggest that women with high and low BD may differ with respect to GM alpha diversity and GM composition.
Citation Format: Lusine Yaghjyan, Xuefeng Wang, Maria Ukhanova, Yessica Martinez, Shannan Rich, Volker Mai, Kathleen Egan. Association of gut microbiome diversity with obesity and breast density in postmenopausal women [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A23.