Why neoadjuvant treatments work differently in different breast cancer subtypes

Research on the Potential Mechanisms Underlying the Efficacy Differences in Specific Neoadjuvant Treatment Regimens for Different Subtypes of Breast Cancer

We will use single-cell and spatial sequencing on tumor samples from people with triple-negative, HR+HER2-, or HR-HER2+ breast cancer to see if molecular differences explain who responds to guideline-recommended neoadjuvant treatments.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 71 (estimated)
• Ages: 25 Years to 75 Years
• Sex: Female
• Sponsor: Xijing Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, trastuzumab, pertuzumab
• Locations: 1 site (Xi'an, Shaanxi)
• Trial ID: NCT07012720 on ClinicalTrials.gov

What this trial studies

This is a single-center, open-label prospective cohort enrolling approximately 71 patients across three breast cancer subtypes (triple-negative, HR+HER2-, HR-HER2+) who will receive neoadjuvant regimens aligned with 2023 CSCO guidelines. Patients will be classified as responders or resistant based on imaging and clinical evaluation, and tumor tissue will be collected before and after therapy. A subset of cases from each subgroup will undergo single-cell RNA sequencing and spatial transcriptomics to compare intratumoral and microenvironmental transcriptomic features between responders and non-responders and to track changes induced by treatment. The goal is to map molecular patterns that associate with response within each regimen and subtype.

Who should consider this trial

Good fit: Women aged 25–70 with newly diagnosed triple-negative, HR+HER2-, or HR-HER2+ breast cancer who are eligible for guideline-recommended neoadjuvant therapy, have not received prior systemic treatment, can provide tumor tissue, and can give informed consent.

Not a fit: Patients who have had prior systemic breast cancer therapy, cannot provide tumor specimens, have serious comorbid conditions or infections, or fall outside the specified subtypes are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the work could reveal molecular signatures that predict or explain response to neoadjuvant therapies and help tailor treatment choices for different breast cancer subtypes.

How similar studies have performed: Single-cell and spatial transcriptomics have been used in other breast cancer work to reveal treatment-response programs, but applying those techniques across these specific neoadjuvant regimens and subtypes in a coordinated cohort remains exploratory.

Eligibility criteria

Inclusion criteria:

1. Voluntary enrollment, able to understand and sign the informed consent form;
2. Female, aged 25 to 70;
3. Meet the indications for neoadjuvant therapy (based on the indicated population clearly defined in the 2023 CSCO Breast Cancer Diagnosis and Treatment Guidelines);
4. No previous systemic treatment for breast cancer;
5. The neoadjuvant treatment regimen met the inclusion requirements: triple-negative breast cancer (T-EC+antiPD-1/T-EC/antiPD-1) HER2+ HR-breast cancer (EC-THP/HP), HER2-HR+ breast cancer (AI/AI+CDK4/6i);
6. Tumor specimens can be obtained (including puncture, minimally invasive, incision biopsy, and surgery);
7. A complete pathological report can be obtained.

Exclusion Criteria:

1. The patient did not sign the informed consent form;
2. Tumor specimens cannot be obtained (including puncture, minimally invasive, incision biopsy, and surgery);
3. Patients with severe systemic infections or accompanied by other serious diseases;
4. Have received cytotoxic chemotherapy, endocrine therapy, biological therapy or radiotherapy for any previous reason;
5. Does not meet the indications for neoadjuvant therapy;
6. Neoadjuvant treatment regimens are not included in the neoadjuvant treatment regimens defined in this study;
7. Other circumstances where the researcher deems it unsuitable for inclusion. Criteria for Subjects to withdraw from the study (1) All subjects can voluntarily withdraw at any stage of the study without being discriminated against or retaliated against, and their medical treatment will not be affected.

(2) Furthermore, the subjects may withdraw from this study under the following circumstances:

1. Withdrawal decided by the researcher:

   A: The patient does not meet the indications for the above-mentioned designated neoadjuvant regimen; B: In cases where the subjects are not suitable to continue the trial during the research process, such as when the patients cannot tolerate immunotherapy or chemotherapy, the established neoadjuvant treatment plan needs to be terminated; C: Those who accept the neoadjuvant treatment regimen specified in this study and show disease progression in the cycle evaluation need to terminate the neoadjuvant treatment in advance and undergo surgical resection of the tumor tissue.

   D: Adverse events occurred. It was judged by the researchers that continuing to participate in the study would have an adverse impact on the safety of the subjects.

   E: Subjects with poor compliance, which affects the assessment of tolerance; F: The researcher requests the subjects to withdraw from the study for any medical reason; G: The researchers believe that the subjects have other circumstances that make them unsuitable to continue participating in the trial.
2. Voluntary withdrawal of the subjects:

A: The subject was unwilling to continue participating in the study and voluntarily withdrew the informed consent form.

B: Loss to follow-up (Before loss to follow-up, subjects who have completed three visits should be attempted to be contacted).

Where this trial is running

Xi'an, Shaanxi

• Xijing hospital — Xi'an, Shaanxi, China (Recruiting)

Study contacts

• Study coordinator: Ju liang J L Zhang

Conditions Breast Cancer; Single-cell sequencing