Carboplatin Intensified Chemotherapy for TRIple NEgative Breast Cancer(CITRINE)

This is a prospective, single center, randomized, open-labled stage III clinical trial comparing the efficacy and safety of anthracyclin followed by weekly paclitaxel versus dose-dense anthracyclin followed by weekly paclitaxel versus dose-dense anthracyclin followed by weekly paclitaxel combined with carboplatin for high-risk, triple-negative early breast cancer.High risk is defined as positive lymph nodes or negative lymph nodes but ki-67 is not less than 50%. We aim to explore whether the addition of carboplatin can improve the disease-free survival of early high-risk triple-negative breast cancer. At the same time, the experimental group's anthracyclines must be given in a dose-dense manner, while anthracyclines in the control group are dose-dense or not.

Inclusion criteria

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Histologically documented TNBC after early breast cancer surgery (absence of HER2, ER, and PR expression)
• Has adequate organ function meeting the following criteria: (1) adequate bone marrow function: hemoglobin ≥ 90 g/L (no blood transfusion within 14 days); absolute neutrophil count ≥ 1.5 x 109 /L; platelet count ≥ 75 * 109 /L; (2)adequate liver and kidney function: Alanine Aminotransferase (ALT) ≤ 3×upper limit of normal (ULN), Aspartate Aminotransferase (AST) ≤ 3×ULN, Total Bilirubin (TBIL)≤ 1.5×ULN, serum creatinine ≤ 1×ULN#and with endogenous creatinine clearance rate of >50 ml/min (Cockcroft-Gault formula).
• Women aged 18-70 years old;
• Lymph nodes positive or lymph nodes negative but with ki67 no less than 50%
• Have the cognitive ability to understand the protocol and be willing to participate and to be followed up
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm

Exclusion criteria

• Has received neoadjuvant therapy (include chemotherapy, targeted therapy, radiotherapy or endocrine therapy;
• Has bilateral breast cancer;
• Has previous history of additional malignancy, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ.
• Has metastatic breast cancer
• Is pregnant, is breast feeding women, or women of childbearing age who cannot practice effective contraceptives;
• Patients participating in other clinical trials at the same time;
• Has severe organ dysfunction (cardiopulmonary liver and kidney) insufficiency, left ventricular ejection fraction (LVEF) < 50% (cardiac ultrasound); severe cardio cerebral vascular disease within the 6 months previous of randomization (such as unstable angina, chronic heart failure, uncontrolled hypertension with blood pressure>150/90mmgh, myocardial infarction, or cerebral blood vessel); diabetic patients with poor blood glucose control; patients with severe hypertension;
• Has known allergy to taxane
• Has severe or uncontrolled infection;
• Has a history of psychotropic substance abuse and were unable to abandon drug habits, or those with history of mental disorders;
• the researchers judged patients to be unsuitable for the study.