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 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 HER2 Negative Breast Adenocarcinoma Hormone Receptor Positive Breast Adenocarcinoma Invasive Breast Carcinoma Multifocal Breast Carcinoma 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 Unilateral Breast Carcinoma Ability to understand and the willingness to sign a written informed consent document Females (regardless of menopausal status), or males of all races and ethnic groups Biopsy proven estrogen receptor (ER) and/or progesterone receptor (PR) positive as defined as ER >= 1% and/or PR >= 1% by immunohistochemistry according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing HER2 non-amplified per 2018 ASCO/CAP guidelines, defined as Immunohistochemistry (IHC) score 0/1+, or IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells; or ISH non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells Clinical T1-T3, any N, M0 invasive breast cancer, by American Joint Committee on Cancer (AJCC) 8th edition clinical staging with the goal being curative intent surgery to completely excise involved tumor in the breast and the draining lymph nodes Individuals with unilateral, multi-focal breast cancer (defined as more than one lesion of invasive breast cancer in the same breast separated from the dominant breast lesion by less than 5 cm of radiologically normal breast tissue) are eligible Participants must be planned for neoadjuvant chemotherapy  Prior history of malignancy within 5 years except for successfully treated cervical carcinoma in situ, lobular carcinoma in situ of the breast, or non-melanoma skin cancer Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema) is not eligible Participants that have undergone surgical axillary staging procedure prior to study entry Fine needle aspiration (FNA) or core needle biopsy of axillary node is permitted Bilateral breast cancer, provided tumors exhibit similar biomarkers (grade, ER/PR, HER2) Clinical or radiographic evidence of metastatic disease Isolated ipsilateral supraclavicular node involvement is permitted A prior history of ductal breast carcinoma in situ (DCIS) treated with contralateral mastectomy and not receiving endocrine therapy is eligible Breast implants are contraindicated only if the implant precludes the required research biopsies or interferes with palpating the breast lesion Prior treatment for this cancer including surgery, radiation therapy, chemotherapy, biotherapy, hormonal therapy or investigational agent prior to study entry