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,  Anatomic Stage 0 Breast Cancer AJCC v8 Anatomic Stage I Breast Cancer AJCC v8 Anatomic Stage IA Breast Cancer AJCC v8 Anatomic Stage IB Breast Cancer AJCC v8 Anatomic Stage II Breast Cancer AJCC v8 Anatomic Stage IIA Breast Cancer AJCC v8 Anatomic Stage IIB Breast Cancer AJCC v8 Anatomic Stage IIIA Breast Cancer AJCC v8 Anatomic Stage IIIB Breast Cancer AJCC v8 HER2/Neu Negative Invasive Ductal Carcinoma, Not Otherwise Specified Progesterone Receptor Negative Prognostic Stage 0 Breast Cancer AJCC v8 Prognostic Stage I Breast Cancer AJCC v8 Prognostic Stage IA Breast Cancer AJCC v8 Prognostic Stage IB Breast Cancer AJCC v8 Prognostic Stage II Breast Cancer AJCC v8 Prognostic Stage IIA Breast Cancer AJCC v8 Prognostic Stage IIB Breast Cancer AJCC v8 Prognostic Stage IIIA Breast Cancer AJCC v8 Prognostic Stage IIIB Breast Cancer AJCC v8 Triple-Negative Breast Carcinoma Written informed consent must be obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 Localized, palpable, biopsy proven triple negative or ER positive HER2 negative infiltrating ductal breast cancer with size > 1.5 cm by palpation, excluding breast cancer where neoadjuvant chemotherapy is indicated by current guidelines (i.e. inflammatory subtype, etc.) Tumor that is palpable and injectable Hemoglobin >= 9 g/dL Absolute neutrophil count >= 1,500/mm^3 Platelet count >= 100,000/mm^3 Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal (ULN) Bilirubin =< 1.5 x ULN; for subjects with documented/suspected Gilbert?s disease, bilirubin =< 3 x ULN Albumin >= 2.5 g/dl  Contraindications to tumor biopsy and injections (coagulopathy, known history of keloid formation, etc.) Women who are pregnant or breastfeeding Sexually active subjects and their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec Inability to give informed consent History of malignancies except cured basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix; for other malignancies, must be documented to be free of cancer for >= 2 years. All other cases can be considered on a case by case basis at the discretion of the principal investigator Any condition that might interfere with the subject?s participation in the study, safety, or in the evaluation of the study results Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study Prior exposure to any anti-PD-1 or anti-PD-L1 antibody, or any anti-CTLA 4 antibodies Patients must not have received prior treatment with talimogene laherparepvec or other oncolytic virus agents Patients must not have received any live vaccine within 30 days prior to registration. Seasonal flu vaccines that do not contain live virus are permitted