The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, hormone receptor positive (HR+), human epidermal receptor 2 negative (HER2-), breast cancer.

Inclusion Criteria:

• Women (regardless of menopausal status) or men ≥18 years of age (or per local regulations).

• The participant has confirmed HR+, HER2-, early stage resected invasive breast cancer without evidence of distant metastases.

• The participant must have undergone definitive surgery of the primary breast tumor.

• The participant must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization.

• Pathologic lymph node involvement and at least one of the following indicating a higher risk of recurrence:

  • 4 or more positive axillary lymph nodes
  • Tumor size of at least 5 centimeters
  • Grade 3 defined as at least 8 points on the Bloom Richardson grading system
  • Ki-67 index by central analysis of ≥20% on untreated breast tissue

• The participant must be randomized within 16 months from the time of definitive breast cancer surgery.

• The participant may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation) whichever is last.

• Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and radiotherapy and from surgical side effects following definitive breast surgery.

• Women of reproductive potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods.

• The participant has a Eastern Cooperative Oncology Group (ECOG) performance status ≤1.

• The participant has adequate organ function.

• The participant is able to swallow oral medications.

Exclusion Criteria:

• Metastatic disease (including contralateral axillary lymph nodes) or node-negative disease.
• Participants with inflammatory breast cancer.
• Participants with a history of previous breast cancer, with the exception of ipsilateral ductal carcinoma in situ (DCIS) treated by locoregional therapy alone ≥5 years ago. Participants with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Participants with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years from the date of randomization are excluded.
• Females who are pregnant or lactating.
• The participant has previously received treatment with any CDK4 and CDK6 inhibitor.
• The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate).
• The participant has previously received endocrine therapy for breast cancer prevention (tamoxifen or aromatase inhibitors) or raloxifene.
• The participant has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
• The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin or sudden cardiac arrest. Any participant with a history of venous thromboembolism (VTE).
• The participant has active systemic infections or viral load.
• The participant has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.