This study tests a new treatment approach for people with early-stage triple negative breast cancer whose tumors have a high number of immune cells, called tumor-infiltrating lymphocytes or TILs, as seen by a pathologist on tissue review. A high TIL count is a sign the cancer may respond especially well to chemotherapy and immunotherapy together, meaning more toxic treatment may not be needed for everyone.
All patients with high TILs will receive 12 weeks of chemotherapy (carboplatin and paclitaxel) with the immunotherapy drug pembrolizumab before surgery, without anthracyclines, a class of chemotherapy drugs that is effective but carries risks of heart damage and, rarely, bone marrow disorders or leukemia. Patients with no cancer found at surgery continue on pembrolizumab alone. Those with residual cancer receive anthracycline-based chemotherapy plus pembrolizumab, closer to current standard treatment.
The goal is to personalize treatment, sparing anthracyclines for patients likely to do well without them while reserving stronger therapy for those who need it. The main measure of success is the pathologic complete response rate, with cancer-free survival and overall survival also assessed.
Age ≥ 18 years at the time of informed consent.
Ability to understand and willingness to sign a written informed consent document in accordance with institutional and federal guidelines.
Histologically confirmed diagnosis of triple-negative breast cancer (TNBC) or hormone receptor-low invasive breast carcinoma, with clinical anatomic Stage II or Stage IIIA/B as defined by the AJCC 8th Edition Anatomic Breast Cancer Staging System.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Presence of N3, inflammatory, or metastatic (M1) breast cancer.
Adequately treated non-melanoma skin cancer, or
Cervical carcinoma in situ, or
Other malignancies with a ≥3-year disease-free interval. Prior and Concurrent Therapy
Single group
Carboplatin
DrugTarget AUC 5 every 3 weeks for 12 weeks (depending on response) OR Target AUC 1.5 every week for 12 weeks (depending on response).
Paclitaxcel
Drug80 mg/m2 every week for 12 weeks.
Pembrolizumab
Drug200 mg every 3 weeks for 4-6 cycles (depending on response).
Rate of pCR in breast and axilla
proportion of patients who experience a pathologic complete response (pCR) and report an exact binomial (Clopper-Pearson) 95% confidence interval (CI) to convey precision
Event-free survival (EFS)
the time from the start of treatment to the first occurrence of any of the following events: disease progression during NAC, failure to undergo surgery due to progression or toxicity, local, regional or distant recurrence, or death from any cause.
Overall survival
time from the start of treatment until death from any cause.
Quality of life (QOL)
will be assessed using EORTC QLQ-C30 at baseline, at the conclusion of neoadjuvant chemotherapy (NAC) , and at 6 and 12 months post-NAC.
Incidence and Severity of Adverse Events
Frequency and grade of adverse events per CTCAE v5.0.
Near-pCR Rate (RCB 0/1 rate)
Proportion of patients achieving RCB 0 or 1 post-neoadjuvant therapy.
Radiographic Response Rate (RRR)
Proportion of patients achieving complete or partial response per RECIST v1.1
Invasive Disease-Free Survival (iDFS)
Time from definitive surgery to the first occurrence of an invasive disease event, including local or regional invasive recurrence, distant recurrence, contralateral invasive breast cancer, a second primary invasive malignancy, or death from any cause. Patients without an event will be censored at the date of last follow-up.
Distant disease-free survival (DDFS)
Time from surgery to recurrence at a distant site or death from any cause, whichever occurs first.
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Medical University of South Carolina
Lead sponsor
State University of New York - Upstate Medical University
Collaborator
