• Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses

‣ If a patient declines to participate in any voluntary exploratory research and/or genetic component of the study, there will be no penalty or loss of benefit to the patient and he/she will not be excluded from other aspects of the study

• Women aged at least 18 years

• The patient has a biopsy-confirmed diagnosis of recurrent, unresectable, locally advanced, or metastatic HER2neu-negative breast cancer (including bone-only metastatic disease) o The patient must have had biopsy confirmation of a metastatic site (with appropriate ER/PR/HER2neu IHC staining)

• o The patient has measurable or evaluable disease as evidenced on pre-treatment baseline CT chest, abdomen, and pelvis with bone scan OR PET/CT

• The patient has AR+ breast cancer (defined as \> or equal to 1% staining on immunohistochemistry of metastatic breast cancer specimen)

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks

• If the patient has ER+ or PR+ (\>1% on IHC) metastatic breast cancer:

• o patient must have had 1 prior line of endocrine therapy in the metastatic setting

⁃ prior CDK4/6 inhibitor exposure allowed (abemaciclib. palbociclib, or ribociclib)

⁃ no more than 2 prior line of cytotoxic chemotherapy in the metastatic setting allowed

• If the patient has ER-,PR-, HER2- metastatic breast cancer (triple-negative):

• o The patient may have had up to 4 prior lines of chemotherapy in the metastatic setting and at least 1 prior line of chemotherapy in the metastatic setting

• 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 randomization. A washout period of at least 21 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy).

• Patients who received 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 randomization.

• Post-menopausal status or receiving ovarian ablation with a GnRH agonist such as goserelin or leuprolide. Postmenopausal status is defined by any one of the following criteria:

‣ Prior bilateral oophorectomy.

⁃ Age ≥ 60 years.

⁃ Age \< 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, or ovarian suppression) and FSH, LH, and estradiol in the postmenopausal range per local normal.

∙ If the patient does not meet criteria for postmenopausal status but is receiving ovarian ablation therapy with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin or leuprolide, the patient is eligible for the study, provided that the GnRH agonist is started at least 2 weeks prior to C1D1 of study therapy.

∙ \- Negative serum pregnancy test within 7 days prior to starting treatment

∙ • Women of child-bearing potential and men must agree to use a highly effective method of contraception prior to study entry, for the duration of study participation, and for 3 weeks following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately, as 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.

∙ Note: Recommended methods of birth control are: The consistent use of an intrauterine device (IUD), Double barrier methods (Diaphragm with spermicidal gel or condoms with contraceptive foam), Sexual abstinence (no sexual intercourse) or Sterilization.

∙ Men must agree to use a condom and not father a child or donate sperm for the duration of the study and for 90 days after completion of therapy.

∙ A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).