Impact of Omitting Chemo Based on Patient's Selection for ER-Positive, HER2-Negative Breast Cancer With Ribociclib and Endocrine Therapy

Inclusion Criteria

• •1. Female or male age ≥ 18 years old and have the ability to understand and the willingness to sign a written informed consent document.
• •2. Participants may have ipsilateral or contralateral synchronous breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
• •3. Participants may have multicentric or multifocal breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
• •4. Participants underwent a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
• •5. For participants who undergo a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins.
• •a. Participants with margins positive for LCIS are eligible without additional resection.
• •6. For participants who undergo mastectomy, the margins must be free of residual gross tumor.
• •7. Participants must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
• •8. The following staging criteria must be met postoperatively according to AJCC 8th edition criteria: Men or premenopausal women with T1-3N1-2. Postmenopausal women with T3N1 or T1-3N2 diseases.
• •9. The tumor must be ER-positive (≥ 10%), HER2-negative, by current ASCO/CAP guidelines based on testing results. HER2-negative breast cancer is defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the participant's HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory).
• •10. Oncotype Dx Recurrence Score must be 0 - 25.
• •11. Participants with known menopausal status at the time of screen.
• •a. Postmenopausal status is defined as: i. Participant underwent bilateral oophorectomy, or ii. Age ≥ 60 years, or Age \< 60 years and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression) and Folliclestimulating hormone (FSH) and plasma estradiol are in the postmenopausal ranges per local normal ranges. Note: All women who do not meet the criteria for postmenopausal status are considered premenopausal for the purpose of this trial.
• •12. The interval between the last surgery for breast cancer (including re-excision of margins) and screening must be no more than 16 weeks.
• •13. HIV-infected participants with undetectable viral load within 6 months and in long term anti-retroviral therapy that would not have a significant drug-drug interaction with ribociclib are eligible for this trial.
• •14. Radiation therapy should be used according to standard guidelines.
• •15. Participants must have an ECOG performance status of 0 to 1 within 28 days prior to initiation of the study treatment.
• •16. Participant is able to swallow oral medications.
• •17. Participants must have adequate organ and marrow function as defined below. All laboratory values must be obtained within 14 days prior to screening.
• •1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
• •2. Platelets ≥ 100 × 109/L.
• •3. Hemoglobin ≥ 9.0 g/dL.
• •4. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) formula.
• •5. Alanine transaminase (ALT) \< 2.5 × Upper Limit Normal (ULN).
• •6. Aspartate transaminase (AST) \< 2.5 × ULN.
• •7. Total serum bilirubin \< ULN; or total bilirubin ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN in patients with well documented Gilbert's Syndrome.
• •8. International normalized ratio (INR) ≤ 1.5 (unless the patient is receiving anticoagulants, and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to enrollment).
• •9. Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements (the local laboratory value should be documented within normal limits after the correction) before enrollment:
• •* Potassium.
• •* Magnesium.
• •* Total Calcium (corrected for serum albumin).
• •18. Standard 12-lead ECG values assessed as: QTcF interval (using Fridericia's correction) at screening \< 450 msec. Resting heart rate 50-90 beats per minute (determined from the ECG).
• •19. Participant must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
• •20. Participants must adhere to the following reproductive and contraceptive requirements while on study treatment and for the specified duration after the last dose of the treatment drugs.
• •a. General requirements: i. Participants must not be pregnant or breastfeeding. ii. Participants must not donate or freeze eggs for future use related to assisted reproduction during the course of this study or within three months after receiving the last dose of the study treatment. b. For participants of childbearing potential: i. A participant of childbearing potential is defined as an individual who is premenopausal and capable of becoming pregnant. This includes individuals using contraception, those who are sexually inactive, and those with partners who have undergone a vasectomy. A participant is considered of childbearing potential if they have reached menarche, have not yet met the criteria for postmenopause (defined as more than 12 consecutive months of amenorrhea without any other medical cause), and have not undergone surgical sterilization (such as hysterectomy or oophorectomy).
• •ii. A negative highly sensitive serum pregnancy test (for β-hCG) must be obtained within two weeks of starting the treatment drug administration.
• •iii. Participants must practice at least one highly effective method of contraception.
• •c. Highly effective methods of contraception include, but are not limited to: i. Total abstinence (no sexual relations), when this is in line with the participant's preferred and usual lifestyle. Periodic abstinence like calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception.
• •ii. Total hysterectomy (surgical removal of the uterus and cervix) or tubal ligation (participant's "tubes tied") at least six weeks before taking study treatment. iii. Participant's male partner has already been sterilized with the appropriate documentation. The sterilized male partner should be the sole partner.
• •iv. Placement of an intrauterine device (IUD) v. The use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or intrauterine system (IUS) or any other form of hormonal contraception (e.g., hormone vaginal ring, hormonal-based IUD or transdermal hormone contraception) is not allowed in this study.
• •21. Participant has no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for five years or more.