The LEANORA study

This is a research study to test the combination therapy with the study drug ribociclib (Kisqali) and approved breast cancer drug letrozole or fulvestrant, in the treatment of subjects with hormone receptor positive metastatic breast cancer from different racial groups.

The study aims to determine the pharmacological and biochemical association between ribociclib exposure and CYP3A variants in African American/Blacks and Non-Hispanic White patients.

The findings should allow clinicians to tailor treatments to maintain therapeutic doses while limiting toxicities.

Inclusion Criteria

1. Female ≥18 years old at the time of informed consent.
2. Those who self-identify as African American or Black are eligible for that respective cohort

   Those who self-identify as non-Hispanic White are eligible for that respective cohort

3. Postmenopausal or premenopausal. Patient has a known menopausal status at the time of the informed consent form signature.

The patient is considered postmenopausal if:

1. she has had prior bilateral oophorectomy;
2. is age ≥ 60 years;
3. is age <60 years and has had amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range per local normal ranges.

All other patients who do not meet the criteria for postmenopausal status are considered premenopausal and will receive goserelin for ovarian suppression

Exclusion Criteria

1. Patients with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator’s judgment.
2. Patient currently/actively taking a CDK4/6 inhibitor (e.g., ribociclib, abemaciclib, or palbociclib).
3. Any other prior neo-/adjuvant anti-cancer therapy must be stopped at least 5 half-lives or 7 days, whichever is longer, before the date of ribociclib initiation.

Study Requirements

We expect that participants will be in this research study for one month (during the first cycle of treatment with ribociclib).

Participants will give blood samples during three hospital visits, have electrocardiograms dose during those visits, and provide a cheek cells using a cotton swab.

Participants will also be asked to fill out questionnaires asking about how they feel and if they have forgotten any doses of the medications.

The first and third visit will take as long as usual clinical visits. The second visit is an 8-hour long visit.