Single Cell Immune and Non-immune Correlates of Response to Neoadjuvant Abemaciclib

Inclusion Criteria

• •Clinical stage operable stage I, II, or III invasive mammary carcinoma, which is estrogen receptor or progesterone receptor positive by immunohistochemistry and HER2 negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing.
• •Have post-menopausal status, as defined by any of the following: Subjects at least 55 years of age OR Subjects under 55 years of age and amenorrheic for at least 12 months OR follicule stimulating hormone (FSH) values ≥ 40 IU/L and estradiol levels ≤ 40 pg/mL (140 pmol/L) or in postmenopausal ranges per local or institutional reference ranges.
• •Breast tumor ≥1cm in diameter by either physical exam or ultrasound and suitable for pre and post-treatment tissue sampling.
• •Meet either of 2 following criteria, for which neoadjuvant endocrine therapy for 2 weeks is deemed suitable: 1) disease that is planned for surgery as initial therapy, in which 2 weeks of neoadjuvant endocrine therapy is deemed suitable, 2) Disease for which neoadjuvant systemic therapy (either chemotherapy or endocrine therapy) may be planned, in which 2 weeks of neoadjuvant endocrine therapy prior to start of systemic therapy is deemed suitable.
• •At least 18 years of age
• •Performance status ECOG ≤ 2
• •Have adequate organ function (ANC ≥1,500/mcL, Platelets ≥100,000/mcL, Hemoglobin ≥8 g/dL, Total bilirubin ≤1.5 × upper limit of normal, ALT and AST ≤3 × upper limit of normal, Creatinine clearance \>30 mL/minute
• •The patient is able to swallow oral medications
• •Women may have been taking tamoxifen or raloxifene as a preventive agent prior to study entry but must have discontinued the drug for at least 28 days prior to study enrollment.
• •Subjects have ended hormone replacement therapy at least 7 days prior to receiving the first dose of randomized therapy.
• •Ability to understand and the willingness to sign a written informed consent.
• •Note: Contraceptive methods may include an intrauterine device \[IUD\] or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection. Cases of pregnancy that occur during maternal exposures to abemaciclib should be reported. If a patient or spouse/partner is determined to be pregnant following abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome and breast-feeding are to be collected for regulatory reporting and drug safety evaluation.