The goal of this clinical trial is to test whether a "rescue" strategy can turn chemotherapy-resistant triple-negative breast cancer (TNBC) into a curable state. Patients whose tumors fail to shrink after 2 cycles of standard neoadjuvant chemotherapy will receive a short, high-precision course of stereotactic body radiotherapy (SBRT, 24 Gy in 3 daily fractions) to the breast primary tumor, followed by 4 cycles of toripalimab (an anti-PD-1 antibody) combined with albumin-bound paclitaxel plus carboplatin. The main questions are:
Can this SBRT-immuno-chemo triplet raise the pathologic complete response (pCR; no invasive cancer in breast or nodes at surgery)? Can it produce an objective radiologic response (ORR) in at least half of the patients, allowing more breast-conserving operations and fewer mastectomies? Secondary objectives include safety, changes in tumor-infiltrating lymphocytes (TILs), event-free survival, and exploratory biomarkers (whole-exome and RNA-seq, PBMC immunoprofiling) to discover signatures of benefit. Participants will undergo image-guided core biopsies before and after SBRT, provide serial blood samples, and have definitive surgery 3-5 weeks after the last cycle.
Female, age 18-75 years, newly diagnosed invasive breast cancer.
Histologically confirmed triple-negative phenotype: ER < 1 %, PR < 1 % by IHC, HER2 negative (IHC 0/1+ or IHC 2+ with ISH negative).
Clinical stage II-III (T2-4 or N1-3, M0).
Completed 2 cycles of standard neoadjuvant chemotherapy (taxane ± anthracycline ± platinum) and assessed as non-responder: stable disease (SD) or progressive disease (PD) by RECIST 1.1.
Inflammatory breast cancer.
Any other malignancy requiring treatment within the past 3 years (except adequately treated basal-cell skin carcinoma or cervical CIS).
Active autoimmune disease, immunodeficiency, or systemic steroids > 10 mg/day prednisone equivalent within 2 years.
Clinically significant cardiovascular disease (unstable angina, NYHA III/IV heart failure, recent MI).
Second Affiliated Hospital, School of Medicine, Zhejiang University
Lead sponsor