Patient description: The patient is a 42 year-old postmenopausal woman who had a screening sonogram which revealed an abnormality in the right breast. She had no palpable masses on breast exam. Core biopsy was done and revealed a 1.8 cm infiltrating ductal breast carcinoma in the left upper outer quadrant. Lumpectomy was done and the surgical margins were clear. The tumor was HER2-positive and ER/PR negative. Axillary sampling revealed 1 positive lymph node out of 12 sampled. CXR was unremarkable. She is using “well women” multivitamins daily and no other medication. She smokes frequently and consumes alcohol occasionally. She is in a relation with only one partner and has a history of 3 pregnancies and live births. She breastfed all three children.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Breast Cancer Has a localized invasive breast ductal adenocarcinoma, confirmed by the local pathologist, that includes either T1c-T2 (tumor size ≥2 cm), clinical node stage (cN)1-cN2, or T3-T4, cN0-cN2. Note: Inflammatory breast cancer is allowed Has centrally confirmed ER+/HER2-, Grade 3 breast cancer of ductal histology, according to the most recent American Society of Clinical Oncology/College of American Pathologist guidelines Provides a new or recently obtained core needle biopsy, consisting of multiple cores, taken from the primary breast tumor(s) for central determination of HR status (ER and progesterone receptor), HER2, grade, and PD-L1 status Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to initiation of study treatment Male participants must agree to use contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment and refrain from donating sperm during this period Female participants must agree to use effective contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment with pembrolizumab or placebo Has adequate organ function  Has a history of non-infectious pneumonitis that required treatment with steroids or has current pneumonitis Has breast cancer with lobular histology Has bilateral invasive breast cancer Has metastatic (Stage IV) breast cancer Has multi-centric breast cancer (presence of more than 1 tumor in different quadrants of the breast) Has any of the following clinical lymph node staging per current American Joint Committee on Cancer (AJCC) staging for breast cancer staging based on radiological and/or clinical assessment: cN3, cN3a, cN3b, or cN3c Has ER-, progesterone receptor positive breast cancer Has undergone excisional biopsy of the primary tumor and/or axillary lymph nodes or has undergone sentinel lymph node biopsy prior to study treatment Has a known additional, invasive, malignancy that is progressing or required active treatment in the last 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal breast carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment