Oral Aromatase Inhibitors Modify the Gut Microbiome

Study Overview
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Brief Summary
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The purpose of this research is to study the bacteria in participants' gut before receiving a medicine called an aromatase inhibitor for breast cancer and after participants receive medicine for breast cancer.

Detailed Description
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Primary Objective: To describe the microbiome shift of gut microbiome from baseline after 4-weeks and 12-weeks of oral aromatase inhibitor treatment. Secondary Objective To correlate gut microbiome populations with circulating sex hormone metabolite concentrations at baseline and 12 weeks. To describe the correlation of change in the microbiome populations with change in circulating sex hormone metabolite concentrations from baseline to 12 weeks.

Official Title
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Oral Aromatase Inhibitors Modify the Gut Microbiome Effecting Estrogen Bioavailability

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: Fecal swab collection
* Biological: Blood samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic diagnosis in situ or invasive breast cancer for which initiating aromatase inhibitors therapy is recommended or initiating aromatase inhibitors for risk reduction. ECOG performance status 0,1, 2, 3. Age ≥ 18 years HER2+ breast cancer is allowed if patients are on a monoclonal antibody therapy for which a change is not anticipated while on study (12 weeks) and they have been on the monoclonal antibody therapy for at least 4 weeks. Ability to read, understand and evaluate study materials and willingness to sign a written informed consent document. Exclusion Criteria: Have been on antibiotics within 4 weeks of enrollment. Administered chemotherapy less than 4 weeks prior to enrollment. Hormone replacement (defined as only estrogen and/or progesterone replacement) or anti-estrogen therapy within 4 weeks of starting aromatase inhibitors Use of antibody drug conjugate (HER2+ breast cancer) Male breast cancer Any serious and/or unstable pre-existing medical, psychiatric, or other existing condition that would prevent compliance with the trial or consent process

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Aromatase inhibitor for breast cancer treatment<br>Participants will receive their standard of care for breast cancer treatment which includes an aromatase inhibitor. Pre-study assessments will be done at baseline as well as stool and blood samples at baseline, then again at 4 weeks and at 12 weeks during the course of the trial. | Biological: Fecal swab collection<br>* Participants will collect fecal sample at home and either mail in the sample, or drop it off at the lab<br>Biological: Blood samples<br>* Participants will have approximately 1 teaspoon of blood withdrawn from a vein, for research, on 2 different occasions. The total amount of blood withdrawn during the study will be approximately 2 teaspoons.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gut Microbial Levels - Fecal Swab | To describe the microbiome shift of gut microbiome from baseline after 4-weeks and 12-weeks of oral aromatase inhibitor treatment Investigators will calculate the change in gut microbial levels using paired t-tests. | At baseline, 4 weeks and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gut Microbial Levels - Blood Samples | Investigators will calculate Pearson or Spearman correlation coefficients between diversity and gut microbial levels and circulating sex hormone metabolite concentrations at baseline and at 12 weeks. Bacterial derived bioactive compounds, bile acids, and glucuronidated sex hormones will be compared by metabolomics conducted on plasma. | At baseline and at 12 weeks | 
| Change in Sex Hormone Concentrations - Blood Samples | Investigators will fit a model with independent variables of the value (baseline or 12 weeks), and a second variable that represents the change from baseline (will be 0 or the change at 12 weeks). Estrone, estrone-3-glucuronide, and estrone-3-sulfate concentrations will be measured using an ELISA assay conducted on plasma. | At baseline and at 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gut microbiome, Circulating sex hormone metabolite concentrations