A Study on the Use of Fluzoparib Combined With Chemotherapy for Neoadjuvant Treatment of HRD-positive, HR+/HER2- Breast Cancer

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be enrolled in this trial:

1. Female patients with newly diagnosed breast cancer, aged ≥18 years and ≤70 years;
2. Histopathologically confirmed early or locally advanced HR+/HER2- invasive breast cancer, as defined by the latest ASCO/CAP guidelines, meeting the following conditions:

   * HER2-negative: IHC 0/1+ or IHC 2+ with negative ISH;
   * ER-positive: IHC \>1%; PR-positive: IHC \>1%;
   * cT1c or above with positive lymph nodes; cT2 or above with negative lymph nodes must meet at least one of the following: age ≤40 years; Ki67 \>50%; lymphovascular invasion; histological grade III;
   * HRD-positive: defined as HRD score ≥42 points and/or germline BRCA1/2 mutation (pathogenic or likely pathogenic);
   * ECOG performance status 0-1;
3. Presence of at least one measurable lesion according to RECIST 1.1 criteria;
4. Organ function must meet the following requirements:

1\) Hematology

* Absolute neutrophil count (ANC) ≥1.5×109/L (no use of hematopoietic stimulating factors within 14 days before the first administration of the study drug);
* Platelet count (PLT) ≥100×109/L (no blood transfusion within 14 days before the first administration of the study drug);
* Hemoglobin (Hb) ≥90 g/L; 2) Blood biochemistry
* Total bilirubin (TBIL) ≤1.5×ULN;
* Aspartate transaminase and alanine transaminase (ALT and AST) ≤2.5×ULN;
* Blood urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN; 3) Cardiac function
* Echocardiogram: LVEF ≥50%;
* 12-lead electrocardiogram: QTc interval \<470 ms in females. 5. Subjects voluntarily participate in the study and sign the informed consent form.

Exclusion Criteria

Subjects with any of the following conditions are excluded:

1. Tumor-related symptoms and treatment 1) Patients with metastatic breast cancer or bilateral breast cancer; 2) Patients with inflammatory breast cancer; 3) Participation in other drug trials or receipt of any anti-tumor therapy (including endocrine therapy, bisphosphonate therapy, immunotherapy, biological therapy, or tumor embolization) within 4 weeks before enrollment; 4) Previous treatment with PARP inhibitors;
2. Comorbidities/medical history 1) Previous history of other malignant tumors that have received any systemic anti-tumor therapy or local treatment (including surgery and radiotherapy), excluding cured malignant tumors such as carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma; 2) Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome; active hepatitis (hepatitis B, defined as HBV-DNA ≥500 IU/ml; hepatitis C, positive anti-HCV and HCV-RNA above the lower limit of detection by the analytical method) or combined hepatitis B and C co-infection; autoimmune hepatitis; 3) Severe infection within 4 weeks before the first administration, including but not limited to bacteremia requiring hospitalization, severe pneumonia, etc.; or active infection of CTCAE ≥Grade 2 requiring systemic antibiotic treatment within 2 weeks before the first administration, or unexplained fever \>38.5°C during screening/first administration (fever caused by tumors, as judged by the investigator, is allowed); 4) Subjects with a history of or planned allogeneic bone marrow transplantation or solid organ transplantation; 5) Severe heart disease or disorders, including but not limited to:

   * Confirmed history of heart failure or systolic dysfunction (LVEF \<50%);
   * High-risk uncontrolled arrhythmias, such as atrial tachycardia with resting heart rate \>100 bpm, significant ventricular arrhythmias (e.g., ventricular tachycardia), or high-grade atrioventricular block (i.e., Mobitz II second-degree or third-degree atrioventricular block);
   * Angina pectoris requiring anti-anginal medication;
   * Clinically significant valvular heart disease;
   * ECG showing transmural myocardial infarction;
   * Poorly controlled hypertension (systolic blood pressure \>180 mmHg and/or diastolic blood pressure \>100 mmHg);
3. Pregnant or lactating women, women of childbearing potential with positive baseline pregnancy test, or women of childbearing potential unwilling to use effective contraception throughout the trial period;
4. Previous clear history of neurological or psychiatric disorders, including epilepsy or dementia; known history of psychiatric drug abuse, alcoholism, or drug addiction;
5. Any other conditions deemed inappropriate for the study by the investigator.