Gut Microbiota and Diarrhea in Breast Cancer Patients Receiving Pyrotinib

November 24, 2025 updated by: Xinhong Wu, PhD, Hubei Cancer Hospital

Gut Microbiota Changes in Breast Cancer Patients Treated With Pyrotinib and Correlation With Drug-Induced Diarrhea: An Observational Cohort Study

Background:

Pyrotinib is an effective targeted drug for HER2-positive breast cancer, but it very frequently causes diarrhea, which can be severe enough to disrupt treatment and reduce patients' quality of life. The reason why some patients develop diarrhea while others do not is not well understood. Recent research suggests that the community of bacteria in the gut (gut microbiota) may play a key role in this side effect.

What is the purpose of this study? This is an observational study (Phase 1) that aims to understand the relationship between pyrotinib treatment, changes in gut bacteria, and the occurrence of diarrhea. The main goal is to compare the gut bacteria of patients who develop diarrhea while taking pyrotinib with those who do not. Researchers hope to identify specific bacteria that might protect against diarrhea, which could lead to new ways to prevent or treat this side effect in the future.

What will happen in the study? Patients with HER2-positive breast cancer who are being treated with pyrotinib will be invited to participate. They will be divided into two groups: those who experience diarrhea and those who do not. Participants will provide stool samples at specific time points (e.g., 2 and 4 weeks after starting pyrotinib). They will also allow researchers to collect information from their medical records about their clinical condition and diarrhea symptoms. No experimental intervention will be administered in this phase of the study; all patients will receive standard medical care.

Potential Benefits:

Participants will not receive any direct benefit from this observational phase of the study. However, the information gathered may help scientists better understand pyrotinib-induced diarrhea and develop future strategies to help other breast cancer patients manage this side effect more effectively.

Study Overview

Status

Not yet recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study population consists of adult patients (aged 18-75) diagnosed with HER2-positive breast cancer who are currently undergoing treatment with pyrotinib (either as monotherapy or in combination). This is a prospective observational cohort study where participants are not assigned to an intervention but are instead grouped based on the natural outcome of whether they develop drug-induced diarrhea during the observation period. This creates two primary cohorts for comparison: the 'Diarrhea Group' and the 'Non-Diarrhea Group'. All participants will continue their standard pyrotinib treatment and clinical care throughout the study.

Description

Inclusion Criteria:

  1. Patients aged 18-75 years, regardless of gender.
  2. Diagnosed with HER2-positive breast cancer and currently receiving pyrotinib treatment (either as monotherapy or in combination with endocrine therapy), with a treatment duration of ≥ 2 weeks.
  3. Voluntarily agree to participate in this study and provide written informed consent.

Exclusion Criteria:

  1. History of significant gastrointestinal diseases (e.g., inflammatory bowel disease, Crohn's disease, ulcerative colitis, intestinal obstruction) or previous major gastrointestinal surgery.
  2. Recent use (within 1 month) of antibiotics, probiotics, or traditional Chinese medicine intended to alter intestinal function.
  3. Pregnant or lactating women.
  4. Patients who refuse to provide informed consent or explicitly express unwillingness to participate. Patients found not meeting the inclusion criteria after enrollment will be discontinued from the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Diarrhea Group
This cohort consists of HER2-positive breast cancer patients receiving pyrotinib treatment who develop diarrhea (graded as ≥ Grade 1 according to CTCAE v5.0) during the observation period. Participants in this group will provide stool samples and clinical data for comparison with the non-diarrhea group. No study intervention is administered; all patients receive standard medical care.
Non-Diarrhea Group
This cohort consists of HER2-positive breast cancer patients receiving pyrotinib treatment who do not develop diarrhea (Grade 0 according to CTCAE v5.0) during the observation period. Participants in this group will provide stool samples and clinical data, serving as a control for comparison with the diarrhea group. No study intervention is administered; all patients receive standard medical care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in gut microbiota β-diversity between the Diarrhea group and the Non-diarrhea group.
Time Frame: Through study completion, an average of 6 months.
Beta diversity (e.g., using UniFrac distance) of the gut microbiota will be compared between the two groups based on metagenomic sequencing data. A statistically significant difference (P < 0.05) is expected.
Through study completion, an average of 6 months.
Identification of specific bacterial species enriched in the Non-diarrhea group.
Time Frame: Through study completion, an average of 6 months.
Metagenomic sequencing data will be analyzed to identify bacterial species that are significantly more abundant in the Non-diarrhea group compared to the Diarrhea group, using statistical methods such as LEfSe (Linear Discriminant Analysis Effect Size) with a threshold of LDA Score > 2 and P < 0.05.
Through study completion, an average of 6 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in gut microbiota α-diversity between groups.
Time Frame: Through study completion, an average of 6 months.
Alpha diversity indices (e.g., Shannon index, Chao1 index) of the gut microbiota will be compared between the Diarrhea and Non-diarrhea groups.
Through study completion, an average of 6 months.
Differences in metagenomic functional pathways between groups.
Time Frame: Through study completion, an average of 6 months.
Metagenomic sequencing data will be annotated using databases like KEGG. The abundance of functional pathways (e.g., KEGG Level 2 or 3) will be compared between the two groups to identify differentially abundant metabolic or functional modules.
Through study completion, an average of 6 months.
Differences in serum inflammatory cytokine levels between groups.
Time Frame: Through study completion, an average of 6 months.
Levels of systemic inflammatory cytokines (e.g., IL-6, TNF-α, CRP) measured in serum samples by ELISA or other assays will be compared between the Diarrhea and Non-diarrhea groups.
Through study completion, an average of 6 months.
Differences in serum metabolomic profiles between groups.
Time Frame: Through study completion, an average of 6 months.
Metabolomic profiling of serum samples will be performed (e.g., by mass spectrometry). The metabolic profiles will be compared between the two groups to identify differentially abundant metabolites.
Through study completion, an average of 6 months.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Predictive potential of baseline gut microbiota for pyrotinib-induced diarrhea risk.
Time Frame: Through study completion, an average of 6 months.
An exploratory analysis to assess whether the composition and features of the gut microbiota before starting pyrotinib treatment (baseline) can predict the subsequent risk of developing diarrhea during treatment. Metagenomic sequencing data from baseline stool samples will be used to build predictive models.
Through study completion, an average of 6 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hubei Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2025

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

November 24, 2025

First Submitted That Met QC Criteria

November 24, 2025

First Posted (Estimated)

December 4, 2025

Study Record Updates

Last Update Posted (Estimated)

December 4, 2025

Last Update Submitted That Met QC Criteria

November 24, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LLHBCH2025YN-087

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The Individual Participant Data (IPD) collected in this study will not be made publicly available. The primary reasons are to protect patient privacy and confidentiality, as the dataset contains detailed genetic (metagenomic) and clinical information that could potentially be used to identify individuals. Furthermore, the data is integral to ongoing and future research by the investigative team, including the development of synthetic probiotics, which may involve intellectual property considerations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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