BRE-08 Phase II Study of CMC Regimen for Early Stage Breast Cancer

Inclusion Criteria: I• Age ≥ 18 years of age at time of consent * ECOG performance status 0, 1, or 2 * Histologically confirmed invasive breast cancer documented by biopsy or surgical excision. * Underwent potentially curative resection of primary breast tumor(s) with no gross residual local-regional disease (patients with microscopically positive margins are eligible if adjuvant radiotherapy is planned), with most recent breast or axillary surgery \< 90 days prior to date of signed consent. * No evidence of distant metastatic disease * No prior systemic therapy for this cancer other than pre-operative endocrine therapy * Treating Oncologist recommends adjuvant chemotherapy without concurrent biologic/targeted therapy. Patients may receive a CDK4/6 inhibitor after completion of all study treatment, concurrently with adjuvant endocrine therapy. Patients with a germline pathogenic/likely pathogenic variant in a DNA homologous repair gene (e.g. BRCA1, BRCA2, PALB2) may receive adjuvant PARP inhibitor therapy after completion of all study treatment. * Tumor is estrogen receptor (ER)-positive (\> 10% by IHC) and/or progesterone receptor (PR)-positive (\> 10% by IHC), HER2-negative by IHC or FISH according to 2018 ASCO-CAP guidelines. * AJCC pathologic stage: o pT1-3/pN0-2 based on sentinel lymph node biopsy or axillary dissection * High risk gene expression profile (either luminal B on MammaPrint/BluePrint, or Recurrence Score \> 25 on Oncotype Dx). Study participants are not required to have a high-risk gene expression profile if they have a clinical high-risk tumor, defined as: Age \< 50 and any of the following: * Involvement of 1-3 axillary lymph nodes with metastatic carcinoma (pN1mic/N1) * grade 1 tumor \> 3 cm; or grade 2 tumor \> 2 cm; or grade 3 tumors \> 1 cm (size based on pathological assessment of the maximal dimension of the invasive component of the tumor) * pT1c-T2 and Ki-67 \> 20% * Presence of lymphovascular invasion stage IIIA (pT3/pN1 or pT1-3/pN2) Age \> 50 and any of the following: * Primary tumor \> 5 cm (pT3) * stage IIIA (pT3/pN1 or pT1-3/pN2) * Adequate organ function as defined in Table 1. All screening labs to be obtained within 30 days prior to registration. * Patients with synchronous bilateral primary breast tumors or multiple ipsilateral primary breast tumors are eligible if the treating Oncologist determines that the CMC regimen is appropriate therapy for all primary tumors requiring chemotherapy. * Able to provide written informed consent and HIPAA authorization for release of personal health information. * Women of childbearing potential must agree to use 2 methods of birth control, at least one being a barrier form of contraception if they are sexually active with a male partner unless they are considered highly unlikely to conceive as defined in section 8.6, and cannot be pregnant or breast-feeding. A negative serum or urine pregnancy test is required per institutional practice guidelines. * As determined at the discretion of the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. * Patients with history of HIV/AIDS (acquired immunodeficiency syndrome) are eligible for this study if they are receiving anti-retroviral therapy and it does not include any medications known to alter metabolism or tolerability of component drugs in the CMC regimen (see Appendix), and either of the following criteria are met: * Patients without a history of AIDS-defining opportunistic infections. * Patients with a history of AIDS-defining opportunistic infections, but they have not had an opportunistic infection within the past 12 months. * Patients with Hepatitis B (HBV): chronic carriers of HBV infection (HBsAg-positive) or individuals who have serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and anti-HBc-positive) are eligible if they are receiving appropriate suppressive antiviral therapy that does not include medications known to alter metabolism or tolerability of component drugs in CMC (see Appendix) prior to initiation of cancer therapy, and liver function tests meet study eligibility criteria. * Patients with Hepatitis C (HCV): patients with a history of HCV infection who have completed curative antiviral treatment are eligible if the HCV RNA viral load is below the limit of quantification within 90 days of study enrollment. Patients on concurrent HCV treatment must have HCV RNA viral load below the limit of quantification within 30 days of study enrollment. Patients must also meet liver function test eligibility requirements and antiviral therapy does not include medications known to alter metabolism or tolerability of component drugs in CMC. Exclusion Criteria Subjects meeting any of the criteria below are ineligible for this study: * Prior cytotoxic chemotherapy for this breast cancer * Any investigational agents administered during or within 2 weeks prior to start of CMC chemotherapy * AJCC stage IIIB-IIIC or stage IV * Active infection requiring systemic therapy * Untreated HIV/AIDS * Documented DYPD deficiency * Pregnant or nursing * Require anticoagulation with warfarin. Anticoagulation with low molecular weight heparins, heparin, or direct oral anticoagulants (DOACs) is permitted. * Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this investigational regimen, as determined by the treating medical oncologist. * Any mental or medical condition that prevents the patient from giving informed consent or participating in the trial. * Other major comorbidity (e.g. advanced cardiopulmonary disease, uncontrolled diabetes mellitus) that may affect the safety or efficacy assessment of this investigational regimen, as determined by study PI * Inability to swallow pills * Any medical condition interfering with absorption of oral medications * Any contraindication for any chemotherapy drug used in the CMC regimen * Active and ongoing use of medicines known to alter metabolism or tolerability of component drugs in CMC. * Prisoners * Unable or unwilling to take a large number of oral pills