Examining the Impact of Cholecystectomy and the Microbiota in Breast Cancer Tissues in Breast Cancer Patients at Wake Forest Baptist Medical Center

Background:A healthy microbiome Is associated with high species diversity and richness promoting an anti-inflammatory environment. Changes in this microbiome, particularly pro-inflammatory, have been studied as a risk factor for local and systemic disease and cancer development through promoting tumor growth and spread. There have been published findings that the microbiome in breast tissue and the gastrointestinal tract may contribute to breast cancer development, progression, and recurrence. Studies show that changes in bile acid concentrations may influence the growth of breast cancer in vitro, suggesting that naturally occurring bile acids may also influence the growth of human breast cancer cells through alterations in the microbiome. Therefore, women who have undergone a cholecystectomy could be at higher risk of breast cancer development, progression, and recurrence due to altered modulation of bile acid metabolites. This study aims to evaluate the rate of cholecystectomy in breast cancer patients and their outcomes through retrospective data analysis. The microbiome of breast tumor tissue and blood samples in patients with ER/PR+ HER2- breast cancer collected since 2014 will also be examined to determine discrepancies between the breast microbiota of women who have had a distal recurrence within ten years of diagnosis and those who have not. With an estimated one in eight women in the United States being diagnosed with breast cancer during their lifespan, the results of this study in potentially reducing their risk of recurrence is crucial.

Hypothesis: Women with breast cancer and history of cholecystectomy will have increased rates of breast cancer recurrence over a 5-year period compared to women with breast cancer and intact gallbladders. The breast tumor microbiome varies amongst women who have had a recurrence within 10 years of diagnosis in ER/PR+ HER2- breast cancer. 

Methods: An IRB approved retrospective review of patients with invasive breast cancer diagnosis between 2014-2015 was conducted with data from over 300 patients. Demographics, preoperative variables, surgical history, treatment, and clinical outcome data was collected. Breast tumor samples of thirty patients with ER/PR+ HER2- breast cancer, fifteen of which had recurrence in ten years and fifteen patients with no recurrence, will be evaluated for microorganisms and inflammatory properties.

Results: Results are expected to conclude that women with breast cancer who had a history of cholecystectomy had increased rates of breast cancer recurrence over a 5-year period compared to women with breast cancer and intact gallbladders. Significant differences in the microbiome of patients with and without ER/PR+ HER2- recurrences are expected to be found. 

Conclusions: Further studies with larger patient sample may lead to greater statistical significance and more conclusively support existing studies demonstrating that bile acids influence the growth of breast cancer cells. This makes women with a history of cholecystectomy at higher risk of breast cancer recurrence and may warrant closer follow-up of these patients. More extensive understanding of the breast tumor microbiome may aid physicians further in identifying patients at higher risk of recurrence. 

Source of mentor’s funding or other support that funded this research: The Project described was supported by T35 Training Grant DK007400 from the National Institute of Diabetes and Digestive and Kidney Diseases.