Neo-Adjuvant Abemaciclib With Fulvestrant in Patients With ER/PR +HER Negative Breast Cancer

Inclusion Criteria

• •Patients must have a diagnosis of HR+ breast cancer. To fulfill the requirement of HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least one of the hormone receptors (ER, progesterone receptor \[PgR\]) as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines (Hammond et al. 2010):
• •1\. For ER and PgR assays to be considered positive, ≥1% of tumor cell nuclei must be immunoreactive by immunohistochemistry (IHC) (Hammond et al. 2010).
• •Patients must have Loco regional breast cancer (Stage I, Stage II and stage III per AJCC 8th edition criteria for staging of breast cancer)
• •Patients must have localized recurrence while on adjuvant endocrine therapy
• •Patients must have any known molecular evidence of endocrine resistance by next generation sequencing
• •Age ≥ 18 years.
• •ECOG performance status 0-1
• •Have post-menopausal status as defined by following:
• •1. Prior bilateral oophorectomy
• •2. Age ≥ 60 years
• •3. Age \< 60 and amenorrheic (non-treatment-induced amenorrhea secondary to tamoxifen, toremifene, ovarian suppression, or chemotherapy) for at least 12 months. Follicle-stimulating hormone (FSH) and estradiol must be in the postmenopausal range.
• •Have at least one measurable disease as defined per RECIST 1.1
• •Adequate organ and marrow function as defined below:
• •1. Hemoglobin\* \> 8 g/dL
• •2. Absolute neutrophil count ≥ 1,500/mcL
• •3. Total bilirubin ≤ 1.5 X institutional ULN, Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted
• •4. AST (SGOT)/ALT (SPGT) ≤ 2.5 X institutional ULN
• •5. Creatinine ≤ 1.5 X institutional ULN
• •1. \*Patients may receive transfusion of packed red blood cells (PRBC) to achieve this hemoglobin level at the discretion of the investigator; however, initial study drug treatment must not begin earlier than the day after the PRBC transfusion.
• •Able to swallow oral medications
• •Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and screening for the study.
• •Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A washout period of at least 21 days is required between last chemotherapy dose and enrollment (provided the patient did not receive radiotherapy).
• •Any known markers of response or resistance to CDK 4/6 inhibitors to be present in the biopsy specimen
• •If patients have been treated with prior Neo-Adjuvant chemotherapy at the time of primary diagnosis and not at the time of recurrence, they will be included in the study.
• •Must be able to sign a written informed consent, are reliable, willing to be available for the duration of the study and are willing to follow study procedures