Study to Evaluate Biomarkers and Safety of Dapagliflozin Concomitant With Neoadjuvant Therapy

Inclusion Criteria: Women with newly diagnosed, histologically confirmed, clinical stage I-III, HER2-negative, invasive breast cancer as defined by ASCO CAP guidelines for whom neoadjuvant chemotherapy would be indicated. The following chemotherapy regimens are acceptable Weekly paclitaxel, followed by dose dense doxorubicin plus cyclophosphamide Docetaxel plus cyclophosphamide Docetaxel plus carboplatin Paclitaxel plus carboplatin concurrent with every 3 week pembrolizumab followed by dose dense doxorubicin plus cyclophosphamide concurrent with every 3 week pembrolizumab (KEYNOTE-522 regimen; only for participants with triple negative breast cancer) BMI ≥ 25 kg/m2 Hyperinsulinemia defined as HOMA-IR ≥ 2.5. Willing and able to provide written informed consent/assent for the trial. Has sufficient archival breast cancer tissue available from the diagnostic biopsy OR if not, is willing to undergo a baseline core needle ultrasound guided breast research biopsy for biomarker analysis prior to day 1 of study. Willing to undergo an on-treatment research tumor biopsy after 12 weeks of treatment. Female participants of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication given that all participants will be receiving cytotoxic chemotherapy as part of the treatment regimen, the effects of which can be harmful for the developing fetus. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. All participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Non-childbearing potential in women is defined as postmenopausal status without menses for at least 1 year and an FSH value in the postmenopausal range and/or status post hysterectomy, oophorectomy or tubal ligation. Participants should have adequate organ function to tolerate chemotherapy, as defined by: peripheral granulocyte count of > 1,500/mm3 platelet count > 100,000/mm3 hemoglobin >9 g/dL total bilirubin < 1.5 x upper limit of normal (ULN) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) each < 1.5 x ULN serum creatinine < 1.5 x ULN INR/PT/PTT each < 1.5 x ULN Able to swallow oral formulation of the study agent Subjects should not donate blood while participating in this study, or for at least 90 days following the last dose of chemotherapy Exclusion Criteria: Participants who underwent partial excisional biopsy or lumpectomy, segmental mastectomy or modified radical mastectomy or sentinel node biopsy and therefore cannot be assessed accurately for pathologic response, are not eligible. Participants currently pregnant or breastfeeding. Participants for whom any of the planned chemotherapies are contraindicated. Participants with currently diagnosed type I or II diabetes mellitus. Participants taking any antidiabetic medication that would affect insulin resistance or hyperinsulinemia (i.e. TZD, GLP-1RA, DPP-4i, SGLT2i, metformin) in the past one month. Participants with history of hypersensitivity reaction to dapagliflozin. Participants with eGFR < 25. History of recurrent (three or more occurrences within 12 months, or two or more occurrences within 6 months) urinary tract infections. Currently participating in weight loss programs or weight change in the past 3 months (> 5% current body weight) or have a history of gastrointestinal surgery. Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, intranasal influenza, rabies, BCG, and typhoid vaccine. Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.