Breast Cancer Clinical Trials

⁃ Pre-Screening Phase:

• 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.

• 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.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

⁃ Screening and Treatment Phases:

⁃ General Eligibility

• 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 \<1% per year when used consistently and correctly, and include: copper intrauterine device (IUD); bilateral tubal ligation/occlusion or other documented surgical sterilization; vasectomized partner with documented azoospermia, provided this is the sole sexual partner; or true sexual abstinence, defined as complete abstinence from heterosexual intercourse, when this is the participant's usual and preferred lifestyle. Use of hormonal contraceptive methods (including combined oral contraceptives, progestin-only pills, injectables, implants, hormonal IUDs, patches, or vaginal rings) is not permitted during the study and for at least 6 months after the last dose of study treatment.

• Willingness and ability to comply with all study procedures, including scheduled visits, treatment plans, laboratory tests, and other protocol-specified requirements.

• Willingness and ability to sign and date written informed consent prior to initiation of any study-specific procedures.

• Disease Characteristics

• Breast and axillary imaging (mammogram, ultrasound, or MRI) must have been completed within 45 days prior to registration.

• Patients with abnormal axillary lymph nodes (identified clinically and/or radiographically) must undergo routine pathological confirmation via image-guided core biopsy or fine needle aspiration.

• Presence of:

∙ Measurable disease in the breast measuring at least 1cm with or without nodal involvement; or

‣ Clinical T0 disease with biopsy-proven regional lymph node involvement (cT0N1-2M0), consistent with an overall anatomic stage II-IIIB classification.

• i. For patients with clinical T0 disease confirmed by mammogram/US and MRI, nodal involvement must be documented by core needle biopsy or fine needle aspiration of an axillary or other regional lymph node demonstrating invasive breast carcinoma prior to initiation of neoadjuvant systemic therapy.

• ii. Patients must not have undergone prior surgical excision of an invasive breast primary tumor that would account for the T0 designation (i.e., T0 must not be the result of complete prior excision of the primary breast lesion).

• Patients with multifocal or multicentric disease are allowed if the dominant tumor is confirmed ER and/or PR ≤10%, and HER2-negative.

• Patients with bilateral breast cancer are eligible if both tumors are HER2-negative.

• Staging scans (e.g., CT chest/abdomen/pelvis with a nuclear bone scan) must be performed to rule out metastatic disease under any of the following conditions:

• a. Two or more abnormal axillary lymph nodes on imaging, or b. Clinical suspicion of metastatic disease, or c. At the discretion of the treating physician.

• Clinical and Laboratory Requirements

⁃ Peripheral neuropathy must be Grade ≤1 per CTCAE v5.0.

⁃ Complete history and physical examination performed within 45 days prior to registration.

⁃ Adequate hematologic and organ function as defined by the following:

⁃ a. Hematologic i. Hemoglobin ≥9.0 g/dL (without transfusion or erythropoietin support within 14 days prior to testing) ii. Leukocytes ≥3,000/μL iii. Absolute neutrophil count (ANC) ≥1,500/μL iv. Platelet count ≥100,000/μL b. Hepatic i. AST (SGOT) and ALT (SGPT) ≤3 × ULN ii. For participants without a history of Gilbert's syndrome, total bilirubin ≤1.5 × upper limit of normal (ULN) iii. For participants with a history of Gilbert's syndrome, total bilirubin ≤5 × ULN c. Renal i. Serum creatinine ≤1.5 mg/dL or creatinine clearance ≥50 mL/min/1.73 m² by Cockcroft-Gault formula.

⁃ ii. Note: Patients with creatinine clearance 30-50 mL/min may be enrolled at the discretion of the Principal Investigator, given that paclitaxel is primarily hepatically metabolized and carboplatin dosing can be adjusted to renal function.

⁃ Cardiac function must be within acceptable limits, as follows: left ventricular ejection fraction (LVEF) ≥50% by

⁃ a. Echocardiogram (ECHO), or b. Multi-gated acquisition (MUGA) scan.

⁃ Participants with known human immunodeficiency virus (HIV)-infection must be on effective antiretroviral therapy (ART) at randomization and have an undetectable viral load test on the most recent test results obtained within six (6) months prior to randomization.

⁃ Participants with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within six (6) months prior to randomization, if indicated.

⁃ a. NOTE: No testing for HBV is required unless mandated by local health authority.

⁃ Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have an undetectable HCV viral load test on the most recent test results obtained within six (6) months prior to randomization, if indicated.

• NOTE: No testing for HCV is required unless mandated by local health authority.