A Phase II Study of Biomarker-Guided De-escalation Using Anthracycline-Free Neoadjuvant Chemoimmunotherapy in Early-Stage Triple Negative Breast Cancer (TNBC) Patients With High Tumor-Infiltrating Lymphocytes (TILs)

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.

Inclusion Criteria: Pre-Screening Phase: 1. Age ≥ 18 years at the time of informed consent. 2. Ability to understand and willingness to sign a written informed consent document in accordance with institutional and federal guidelines. 3. 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. a. Invasive tumor must be estrogen receptor (ER) and/or progesterone receptor (PR) negative or low, defined as ≤10% positive staining by immunohistochemistry (IHC). b. HER2-negative disease, defined in accordance with current ASCO-CAP HER2 testing guidelines. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Screening and Treatment Phases: General Eligibility 1. Individuals of childbearing potential must be willing and able to use highly effective contraception from the time of informed consent, throughout study treatment, and for at least 6 months after the last dose of trial therapy. a. NOTE: Highly effective contraception is defined as methods with a failure rate \