RAGE Inhibition to Decrease Cardiotoxicity in Women With Early Breast Cancer

Inclusion Criteria: 1. Patients must have clinical or pathologic stage I-III, histologically confirmed breast cancer, with any ER (estrogen-receptor), PR (progesterone receptors), or HER2 (human epidermal growth factor receptor 2) status who are planned to receive chemotherapy in the adjuvant or neoadjuvant setting. a. Chemotherapy regimens administered per USPI (United States Prescribing Information) label: i. Dose dense doxorubicin plus cyclophosphamide followed by paclitaxel (ddAC/ddT) for 8 cycles ii. Docetaxel plus cyclophosphamide (TC) for 4-6 cycles iii. Docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP)for 6 cycles iv. Chemotherapy regimen that includes ddAC, given at the end of the chemotherapy plan \[can include: (1)weekly carboplatin + paclitaxel + pembrolizumab followed by pembrolizumab + dose dense doxorubicin and cyclophosphamide; (2) weekly carboplatin + paclitaxel followed by dose dense doxorubicin and cyclophosphamide; (3) weekly or dd paclitaxel followed by dose dense doxorubicin and cyclophosphamide\] 2. Patients must have had no prior chemotherapy/radiotherapy/or systemic therapy for early stage breast cancer, or any other malignancy 3. Age ≥18 years. 4. ECOG (Eastern Cooperative Oncology Group) performance status ≤2 (Karnofsky ≥60%, see Appendix D). 5. Patients must have normal organ and marrow function as defined below: 1. Leukocytes ≥3,000/mcL (microliter) 2. Absolute neutrophil count ≥1,500/mcL 3. Platelets ≥100,000/mcL 4. Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN) 5. AST(SGOT) (aspartate transaminase)/ALT(SGPT) (alanine aminotransferase) ≤1.5 × institutional ULN 6. Glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. 6. Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial. If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated. If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load. 7. No pre-existing neurodegenerative disease or impairment, including history of CVA (cerebrovascular accident), or head injury. 8. No psychiatric disorders which could interfere with their ability to consent. (Allowed psychiatric disorders may include but are not limited to: anxiety, depression, obsessive compulsive disorder, ADHD; as long as the disorder does not affect the ability to consent). Any other psychiatric disorders should be discussed with the Principal Investigator (PI) and will be allowed at the discretion of the PI. 9. The effects of azeliragon on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. 10. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: 1. Patients who have had prior chemotherapy, radiotherapy, systemic therapy, or hormonal therapy 2. Patients with Stage IV breast cancer 3. Patients who are receiving any other investigational agents. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to azeliragon, or the standard of care chemotherapy assigned, including: docetaxel, cyclophosphamide, carboplatin, doxorubicin, paclitaxel, trastuzumab, pertuzumab, pembrolizumab. 5. Patients receiving any medications or substances that are strong CYP2C8 inhibitors are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Subjects who discontinue a strong CYP2C8 inhibitor must have discontinued the drug for at least 5 days or 5 half-lives of the drug, whichever is longer, before the first dose of study drug. 6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, neurogenerative disease/impairment, or psychiatric illness/social situations that would limit compliance with study requirements. 7. Pregnant women are excluded from this study as the risks of azeliragon to a fetus are unknown. There is unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azeliragon; breastfeeding should be discontinued if the mother is treated with azeliragon. These potential risks may also apply to other agents used in this study. 8. History of cancer within the last 5 years except adequately treated cervical carcinoma-in-situ, or cutaneous basal cell or squamous cell cancer.