Gut microbiota in association with chemotherapy treatment

Institution: University of Southern California
Investigator(s): Anna Wu, Ph.D. -
Award Cycle: 2014 (Cycle 20) Grant #: 20IB-0105 Award: $246,936
Award Type: IDEA
Research Priorities
Detection, Prognosis and Treatment>Innovative Treatment Modalities: search for a cure

Initial Award Abstract (2014)

Non-technical overview of the research topic and relevance to breast cancer:
High body weight (or body mass index, BMI) has been found to reduce survival in breast cancer patients. Although women have long been advised to limit weight gain following breast cancer diagnosis, the tools to affect such ends (e.g., physical activity, dietary changes) are often ineffective because of poor adherence. New biotechnologies have now given us methods to study how changes in the gut microbiota (both good and bad bacteria) may affect health and disease. These studies suggest very interesting links between the microbiota and risk of obesity, metabolic disease and inflammatory responses. Two recent studies of cancer patients (none had breast cancer) found significant changes in microbiota after chemotherapy treatment. These findings highlight the need to determine the potential effect of chemotherapy on gut microbiota in breast cancer patients, and to explore whether these changes may, in turn, influence weight gain and how fat is distributed in breast cancer patients. This grant application represents a first step to collect the critical data that will allow us to systemically study the role of gut microbiota in relation to outcome in breast cancer patients.

The question(s) or central hypotheses of the research:
Our aims are: (1) To examine the short-term and long-term effects of chemotherapy on the gut microbiota (composition, abundance, diversity) of women with breast cancer. Specifically, we will compare the gut microbiota communities before the initiation of chemotherapy treatment to the microbiota one month and four months after final chemotherapy; (2) To examine the changes in body size and body composition (fat mass, lean mass, percent fat in trunk and extremities) before and after chemotherapy among all patients and separately by pre-treatment BMI; and (3) To evaluate if pre-treatment body size and composition and/or changes in body size and composition during the study period affect gut microbiota changes.

The general methodology:
This study will be conducted at the Norris Cancer Center and the Los Angeles County (LAC)-USC Medical Center. We will include women ages 40-75, newly diagnosed with incident, invasive, early stage breast cancer, and planning to receive chemotherapy. Eligible patients will be asked to participate in three clinic visits at the Norris (1 week before start of chemotherapy, 1 month after final chemotherapy, and 4 months after final chemotherapy). Before the first clinic visit, we will administer a baseline questionnaire, which will ask about menstrual and reproductive history, family history of cancer, diet, use of medications and supplements, and usual physical activities. Information on tumor characteristics and treatment details will be obtained from the patientsí clinical records. Body composition (percent body fat by region of body) will be measured by dual-energy x-ray absorptiometry (DEXA) at visits 1 and 3. We will also collect vital signs, anthropometric measurements (height, weight, and hip and waist circumferences), dietary and lifestyle assessments, and blood and fecal samples at all three visits. We will use a fecal collection kit that has been designed and tested by our collaborator, Dr. Ravel at the University of Maryland School of Medicine, an expert on microbiome research. Dr. Ravelís laboratory will be responsible for all aspects of the gut microbiota analyses.

Innovative elements of the project:
New research suggests that changes in the gut microbiota during chemotherapy may contribute to weight gain among breast cancer patients. Innovative new biotechnology methods now allow us to assess the bacterial composition, abundance, and diversity of the gut microbiota. We believe studies such as this one will help us to eventually identify increase or loss of specific bacteria that are correlated with changes in body composition, and that the gut microbiota could one day be targeted with medication, diet, or other lifestyle changes. To our knowledge there are no published data on the role of the gut microbiota in breast cancer patients. Results generated from this project will be novel and will provide the necessary information which will be used in the design of future studies.

Progress Report 1 (2015)

This IDEA Award is a one year longitudinal, observational study that has been designed to investigate whether the gut microbiome (i.e., bacterial composition, abundance, and diversity) of breast cancer patients may be changed in association with chemotherapy treatment. Our specific aims are to recruit and follow 45 newly diagnosed breast cancer patients. We plan to: 1) examine the transitory and longer lasting effects of adjuvant chemotherapy on the gut microbiota, 2) examine the changes in body composition before and after chemotherapy among all patients and separately by pretreatment body mass index (BMI), and 3) examine the relationship between changes in the gut microbiota by pretreatment BMI and by changes in body composition in relation to chemotherapy.

We have made substantial progress to accomplish these study aims in year 1.

1) During the first 6 months of study (June 2014 to December 2014), we finalized the study protocol, data collection forms, informed consents, and database management system and obtained approval from the USC Clinical Investigation Committee (CIC) as well as the USC IRB to conduct this study. Upon obtaining institutional approval, funding from the CBCRP commenced in January 2015.

2) We began patient recruitment at the USC Norris Comprehensive Cancer Center and at the Los Angeles County (LAC)+ USC Medical Center in February 2015. To date, 36 newly diagnosed breast cancer patients have been enrolled and they have completed a baseline lifestyle questionnaire and a structured food frequency questionnaire (abbreviated modified BLOCK questionnaire), donated fecal, urine, and blood specimens for the gut microbiome and other analyses, and had a Dual Energy X-ray Absorptiometry (DEXA) scan which provides detailed body composition information (e.g., amount and deposition of body fat, lean tissue in the trunk, arms, and legs, etc.). To accommodate differences in the chemotherapy regimen (number of cycles, total duration) for different patients, our protocol aims to collect a fecal, urine, and blood specimen at the completion of each course of chemotherapy (we expect to obtain approximately 4 different collections from each patient).

We plan to continue patient recruitment using the current protocol with the goal of completing recruitment of all 45 patients by early 2016. Each of the patients will be followed during the duration of the chemotherapy treatment and for 4 months after completion of chemotherapy treatment. Our experience during the first 12 months of field work suggests that we should be able to complete recruitment during the next study period. Analysis of gut microbiome will be conducted in the laboratory of Dr. Jacques Ravel at the University of Maryland at the completion of the study.