Breast Cancer Study of Preoperative Pembrolizumab + Radiation

Inclusion Criteria: * Confirmed histologic diagnosis of invasive adenocarcinoma of the breast, and * ER, PR and HER2 testing (on outside or Cedars-Sinai biopsy report), and * High-risk, ER-positive and HER2-negative breast cancer patients. ER-positive disease is defined as ER\>10%, any PR and HER2-negative by ASCO CAP guidelines. High-risk disease will be defined by the presence of at least 2 of the following 3 criteria: histologic grade II-III, Ki-67 \> 20%, ER expression \< 75% by IHC) * TNBC patients (defined as ER\<10%, PR\<10%, HER2-neu 0-1+ by IHC or FISH-negative; or as per MD discretion) * Operable tumor measuring ≥2 cm in maximal diameter as measured by any available standard of care imaging (mammogram, breast ultrasound, breast MRI) * Any nodal status * Multifocal disease is permitted; largest focus must measure ≥2 cm * Synchronous bilateral invasive breast cancer is permitted * No indication of distant metastases * Breast-conserving therapy is planned * Tumor amenable to preoperative radiation therapy boost as determined by radiation oncologist * ECOG performance status score of 0 or 1 * Screening laboratory values must meet the following criteria: i. White blood cells (WBCs) ≥ 2000/μL ii. Absolute neutrophil count (ANC) ≥ 1500/μL iii. Platelets ≥ 100 x 103/μL iv. Hemoglobin ≥ 11.0 g/dL v. Serum creatinine ≤ 2 mg/dL (or glomerular filtration rate ≥ 40 ml/min) vi. AST ≤ 2.5 x upper limit of normal (ULN) vii. ALT ≤ 2.5 x ULN viii. Total bilirubin within norm…