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.

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.

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.

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.