Triple threat: radiation, chemo, and immunotherapy before breast cancer surgery

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Female patients aged ≥18 and ≤75 years at the time of signing informed consent. 2. ECOG PS status of 0-1. 3. Histologically confirmed non-metastatic (M0) breast cancer, meeting all of the following: a) Clinical stage (per AJCC 8th edition) meeting one of the following: i. cT3N0, cT2-4N1-3, or cT1N2-3 (Stage IIB, IIIA, IIIB, or IIIC); ii. cT2N0 or cT1N1 (Stage IIA) with at least two of the following high-risk features: Histologic grade 3; Ki-67 ≥50%; Age \<50 years and premenopausal status. b) Imaging assessments within 28 days prior to enrollment including: abdominal CT or ultrasound, bone scan (ECT), chest CT, and brain MRI. 4. Histologically or pathologically confirmed invasive carcinoma, with all of the following: 1. Grade 2 or 3 (confirmed by central laboratory); 2. ER-positive (\>1% staining) and/or PR-positive (\>1% staining) by IHC; 3. HER2-negative (IHC 0/1+ or HER2/neu FISH ratio ≤1.8); 4. Ki-67 ≥15%. 5. Patient deemed eligible for radiotherapy after MDT evaluation. 6. No prior antitumor therapy within 1 month before enrollment. 7. Organ Function Requirements (within 7 days prior to enrollment): 1. Complete blood count (no transfusion or hematopoietic growth factors within 7 days): ANC ≥1.5×10⁹/L; ALC ≥0.5×10⁹/L; Platelets ≥100×10⁹/L; Hemoglobin ≥90 g/L; WBC ≥3.0×10⁹/L and ≤15×10⁹/L; 2. Blood biochemistry (no transfusion/albumin within 7 days): ALT/AST ≤2.5×ULN; ALP ≤2.5×ULN；BUN/Cr ≤1.5×ULN; Cr≥60 mL/min (Cockcroft-Gault formula); 3. Coagulation: PT/APTT ≤1.5×ULN; INR ≤1.5×ULN (if no anticoagulant therapy); 4. Urinalysis: Urine protein \<2+; if ≥2+, 24-hour urine protein must be ≤1g; 5. Thyroid function:TSH ≤1×ULN; if abnormal, normal T3/T4 levels required for eligibility. 8. Women of childbearing potential must: 1. Have a negative serum pregnancy test within 7 days before treatment; 2. Use highly effective contraception during the study and for 180 days after the last dose. 9. Voluntarily sign informed consent, demonstrate good compliance, and commit to follow-up. Exclusion Criteria: 1. Inflammatory Breast Cancer. 2. Comorbidities/Medical History: 1. Autoimmune disease: patients with any known or suspected autoimmune disease, except: hypothyroidism due to autoimmune thyroiditis managed with hormone replacement therapy only, stable type-1 diabetes with well-controlled blood glucose. 2. Cardiovascular Diseases: poorly controlled hypertension despite medication (SBP \>140 mmHg or DBP\>90 mmHg). And with the history (within 6 months prior to enrollment) of myocardial infarction, severe/unstable angina, NYHA Class ≥2 heart failure, clinically significant arrhythmias as well as symptomatic congestive heart failure. 3. Interstitial lung disease, non-infectious pneumonitis, or other uncontrolled systemic diseases (e.g., diabetes, pulmonary fibrosis, acute pneumonia); 4. Vaccination: receipt of live attenuated vaccines within 28 days prior to enrollment or planned during the study; 5. Infections: HIV/AIDS, active hepatitis(HBV-DNA ≥500 IU/mL; HCV-RNA above detection limit), or co-infection with HBV and HCV, severe infections within 4 weeks prior to enrollment (e.g., bacteremia, severe pneumonia requiring hospitalization), active infection requiring systemic antibiotics (CTCAE≥Grade 2) within 2 weeks prior to treatment, active tuberculosis within 1 year prior to enrollment; 6. Unexplained fever \>38.5°C during screening (unless deemed tumor-related by the investigator); 7. Malignancy History: other malignancies diagnosed within 5 years prior to enrollment (except adequately treated basal cell carcinoma, squamous cell skin cancer, or cervical carcinoma in situ); 8. Surgery:Major surgery within 28 days prior to enrollment (diagnostic biopsies or PICC line placement are allowed); 9. Transplant: Prior or planned allogeneic bone marrow or solid organ transplant; 10. Neurological: peripheral neuropathy ≥Grade 2; 11. Gastrointestinal: clinically significant bowel obstruction; 12. Thrombotic Events: arterial/venous thrombosis within 6 months prior to enrollment (e.g., stroke, transient ischemic attack, DVT, pulmonary embolism); 13. Bleeding Risk: hemoptysis (≥2.5 mL/day) within 2 months prior to enrollment, clinically significant bleeding within 3 months prior to enrollment (e.g. gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood≥++), and the known bleeding/thrombotic disorders (e.g., hemophilia, coagulopathy, thrombocytopenia, hypersplenism); 14. Coagulation abnormalities (INR \>1.5×ULN or APTT \>1.5×ULN), or requiring long-term anticoagulation (warfarin/heparin) or antiplatelet therapy (aspirin≥300 mg/day or clopidogrel ≥75 mg/day). 3. Treatment-Related Exclusions: 1. Prior systemic targeted therapy or immunostimulants (e.g., interferon, IL-2) within 4 weeks before treatment; 2. Known allergy to the investigational drug (recombinant humanized anti-PD-1 mAb) or its excipients. 4. Clinical Trial Participation: participation in another drug trial within 4 weeks prior to enrollment, or within 5 half-lives of the last investigational drug dose. 5. Substance Abuse: history of drug/alcohol abuse or dependency. 6. Pregnancy/Lactation: pregnant, breastfeeding, or planning pregnancy during the study. 7. Investigator' s Discretion: other conditions that may compromise subject safety or study integrity (e.g., severe lab abnormalities, social factors).