Triple-Negative Breast Neoplasm
Conditions
Keywords
Immune-cold microenvironment, Triple-negative breast cancer, Partial Breast Irradiation, Pembrolizumab, KeyNote-522, Immunochemotherapy
Brief summary
A single-arm, single-institution study to induce phenotypic changes in the tumor microenvironment by delivering 8Gy partial breast irradiation in immune-cold triple-negative breast cancer confirmed by PD-L1 and TILs. Additional tissue biopsy will be performed following radiation therapy. Subsequently, neoadjuvant chemotherapy including Pembrolizumab will be administered to evaluate whether pathological complete response rates are improved.
Detailed description
A single-arm, single-institution study to induce phenotypic changes in the tumor microenvironment by delivering 8Gy partial breast irradiation in immune-cold triple-negative breast cancer confirmed by PD-L1 and TILs. Additional tissue biopsy will be performed following radiation therapy. Subsequently, under the supervision and management of breast surgery and medical oncology research teams, standard neoadjuvant chemotherapy for triple-negative breast cancer including pembrolizumab, paclitaxel, carboplatin, doxorubicin, and cyclophosphamide (KeyNote-522 regimen) will be administered, followed by surgical treatment. Pathological complete response status in surgical specimens will be confirmed and reported by the pathologist. Pathological examination and spatial multiplex analysis will be performed on biopsy and surgical specimens to explore biomarkers with significant changes. As secondary end-points, disease-free survival and overall survival will be assessed.
Interventions
RADIATIONPartial breast-irradiation
First, 8Gy partial breast irradiation will be delivered in immune-cold triple-negative breast cancer (TNBC) confirmed by PD-L1 and TILs. Sequentially, standard neoadjuvant chemotherapy for triple-negative breast cancer including pembrolizumab, paclitaxel, carboplatin, doxorubicin, and cyclophosphamide (KeyNote-522 regimen) will be administered, followed by surgical treatment.
Sponsors
Gangnam Severance Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Breast cancer patients aged 20 years or older with clinical stage IIA or higher on imaging studies * Patients with triple-negative breast cancer confirmed on tissue biopsy * Cold immune tumor environment with tumor-infiltrating lymphocytes (TILs) \<30% and PD-L1 Combined Positive Score (CPS) \<10 on immunohistochemical staining of biopsy specimens * Patients with no prior history of breast cancer * Patients with no prior history of chemotherapy or radiation therapy * Patients scheduled to receive partial breast irradiation * Patients with ECOG performance status of 0-2 * Patients who voluntarily signed the informed consent form for study participation
Exclusion criteria
* Patients with non-triple-negative breast cancer on tissue biopsy * Patients scheduled for surgery without neoadjuvant chemotherapy * Patients with TILs ≥30% or PD-L1 CPS ≥10 on immunohistochemical staining of biopsy specimens (immune-hot tumor) * Patients with recurrent breast cancer or de novo stage IV disease * Patients who have previously received chemotherapy and/or radiation therapy to the ipsilateral breast and chest prior to study participation * Patients unable to receive neoadjuvant chemotherapy and Pembrolizumab * Vulnerable research subjects who are unable to participate voluntarily in the study due to physical/mental disabilities
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathologic complete response | Within 3 weeks after surgical treatment |
Contacts
Primary ContactSung Gwe Ahn, M.D.,Ph.D.
Backup ContactSoong June Bae, M.D.,Ph.D.
Outcome results
None listed