Febrile Neutropenia Clinical Trials

• The patient has signed and dated the informed consent form.

• Age \> 18 years at the time of signing informed consent.

• The patient is a female with known menopausal status at the time of signing informed consent or initiation of adjuvant endocrine therapy (whichever is earlier). Postmenopausal status is defined as: bilateral oophorectomy, age \> 60 years, or age \< 60 years with amenorrhea ≥ 12 months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression), and follicle-stimulating hormone and plasma estradiol levels within the local postmenopausal normal range.

• Histologically confirmed unilateral primary invasive breast cancer, with the date of initial cytological or histological diagnosis within 18 months before enrollment. Patients with multicentric and/or multifocal tumors are eligible if all pathologically examined lesions meet criteria 5 and 6 below.

• Estrogen receptor (ER) and/or progesterone receptor (PgR) positivity in the breast cancer, based on the most recent analyzed tissue sample from the local laboratory.

• HER2-negative breast cancer, defined as negative by in situ hybridization or immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization result is required to confirm HER2-negative status (based on the most recent analyzed tissue sample from the local laboratory).

• The patient has undergone surgical resection with complete tumor removal, negative microscopic margins on the final surgical specimen, and belongs to one of the following categories:

• Anatomic Stage II, with any of the following: T0-2N1, T3N0, T2N0 with Grade 2 and Ki-67 ≥ 20%, T2N0 with Grade 2 and high-risk genomic assay result, T2N0 with Grade 3.

• Anatomic Stage III. High-risk genomic assay is defined as Oncotype DX Recurrence Score ≥ 26, or high-risk group by Prosigna PAM50, MammaPrint, or EndoPredict.

• If clinically indicated, the patient has completed adjuvant and/or neoadjuvant chemotherapy according to guidelines before screening.

• If clinically indicated, the patient has completed adjuvant radiotherapy according to guidelines before screening.

⁃ The patient has no contraindications to the adjuvant endocrine therapy in the trial and plans to receive endocrine therapy for 5 years or longer starting from the randomization date.

⁃ The patient may have received any standard neoadjuvant endocrine therapy at the time of signing informed consent, but enrollment must occur within 12 months of the first endocrine therapy initiation. Note: Endocrine therapy for ovarian suppression or short-term fertility preservation is not considered neoadjuvant/adjuvant endocrine therapy. If the patient is using tamoxifen as adjuvant endocrine therapy, a washout period of 5 half-lives is required before enrollment, during which the patient may take an aromatase inhibitor.

⁃ Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

⁃ Adequate bone marrow and organ function defined by meeting the following local laboratory values:

⁃ Absolute neutrophil count ≥ 1.5 × 10⁹/L Platelet count ≥ 100 × 10⁹/L Hemoglobin ≥ 9.0 g/dL Estimated glomerular filtration rate (eGFR) by MDRD formula ≥ 30 mL/min/1.73m² Alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) Aspartate aminotransferase (AST) ≤ 2.5 × ULN Serum total bilirubin \< ULN; or for patients with documented Gilbert's syndrome: total bilirubin ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN International normalized ratio (INR) ≤ 1.5 (unless the patient is on anticoagulant therapy and the INR is within the expected therapeutic range for that anticoagulant within 7 days before enrollment)

⁃ The following laboratory parameters must be within normal limits or corrected to normal range with supplementation (corrected local laboratory values should be recorded as normal):

⁃ Sodium Potassium Magnesium Total calcium (corrected for serum albumin)

⁃ Standard 12-lead electrocardiogram assessed by the local institution meeting the following:

⁃ Screening QTcF interval \< 450 ms Resting heart rate 50-90 beats per minute (determined by ECG)

⁃ The patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.

⁃ Females of childbearing potential must have a negative serum pregnancy test (for β-hCG) within 14 days before enrollment. Females of childbearing potential must be willing to use highly effective contraception. A female is considered to be of childbearing potential unless she has had natural amenorrhea for 12 months with appropriate clinical features (i.e., age-appropriate history of vasomotor symptoms), or has undergone bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before randomization. In the case of oophorectomy alone, only after the female's reproductive status has been confirmed by subsequent hormone level assessment is she considered not of childbearing potential.

⁃ Contraception must be continued during the trial treatment and for 21 days after treatment discontinuation.