Study on the Safety and Tolerability of Postoperative Radiotherapy Concurrent With CDK4/6 Inhibitors in HR+/HER2- High-Risk Breast Cancer

Study on the Safety and Tolerability of Postoperative Radiotherapy Concurrent With CDK4/6 Inhibitors in HR+/HER2- High-Risk Breast Cancer

The investigators combined postoperative radiotherapy with CDK4/6 inhibitors ± endocrine adjuvant therapy to explore the tolerability and safety of this treatment regimen in HR+/HER2- postoperative high-risk breast cancer patients. During the study, investigators also utilized PRO scales (FACT-B, FACT-ES, FACT-F) to evaluate patients' multidimensional experiences, such as physical function, emotional state, and treatment-related symptoms, thereby obtaining more authentic and reliable data for symptom assessment and patient benefit.

1. The screening and evaluation of patients are conducted within 28 days prior to their enrollment, with the investigator screening subjects who meet the inclusion criteria. Prior to initiating any study-specific procedures or assessments, it is mandatory to obtain a signed informed consent form (ICF) from the subjects. Suitable candidates are selected through a series of consultations and examinations, which include inquiries about the patient's personal information, medical history, family history, marital and reproductive history, postoperative pathology, electrocardiogram (ECG), CT scans, complete blood count (CBC), blood biochemistry, and other relevant laboratory tests, to determine whether the subjects are eligible for enrollment in this study.
2. The patient is orally administered the CDK4/6 inhibitor determined by the dose escalation model one day before radiotherapy. During radiotherapy, patient visits are conducted weekly (±2 days) to record vital signs, adverse reactions, and related management measures, specifically at the following times: 7 days before the start of radiotherapy, the 10th day of radiotherapy, the 20th day of radiotherapy, and the 30th day of radiotherapy. If the patient's radiotherapy is delayed for any reason, the follow-up time should be postponed according to the actual situation. PRO scale questionnaires (FACT-B, FACT-ES, FACT-F) are assessed one day before radiotherapy, on the 14th day of radiotherapy, and on the 28th day of radiotherapy. Follow-up evaluations and PRO scale questionnaire assessments are conducted 2 weeks and 4 weeks after the completion of the combined treatment regimen. After completing the 4-week follow-up period of the combination therapy, the patient may resume the normal oral dosage of CDK4/6 inhibitor medication.
3. Evaluate efficacy and safety through statistical methods to form research conclusions. Conduct data cleaning and preprocessing, safety analysis (incidence and severity of AEs; analysis of the correlation between serious adverse events and treatment), and summarize and report the results.

Inclusion Criteria:

• Age is 18-75 years old, gender is female

• Postoperative pathological examination confirmed HR+, HER2- invasive breast cancer:

  1. ER positivity and/or PR positivity is defined as: all positively stained tumor cells The proportion of tumor cells is ≥10%;
  2. HER2 negativity is defined as: 0/1+ by standard immunohistochemistry (IHC) test; ISH test was negative.

• The time from radical surgery or breast-conserving surgery to randomization shall not exceed 6 months;

• Postoperative pathological examination after radical surgery revealed the presence of lymph nodes in the axilla on the ipsilateral side of the breast lesion.

Metastasis (lymph node micrometastases, ipsilateral internal mammary lymph nodes and supraclavicular lymph nodes are allowed) metastasis, but the number of metastases to the ipsilateral internal mammary lymph nodes and supraclavicular lymph nodes is not included in the positive calculation of sexual lymph nodes), the specific requirements are as follows:

1) The number of lymph node metastases is ≥ 4; 2) When the number of lymph node metastases is 1 to 3, at least one of the following high-risk factors must be met: i. Postoperative pathological examination shows that the diameter of the primary tumor is ≥5cm; ii. The histological grade of the primary tumor is grade III (excluding grade II-III); iii. There is residual invasive cancer in breast lesions after neoadjuvant treatment; iv. Ki-67≥30%.

• Eastern Cooperative Oncology Group (ECOG) physical status score is 0 -2 points.
• With my consent and having signed the informed consent form, I am willing and able to comply with the planned interview.

inspections, study treatment plans, laboratory tests, and other research procedures.

Exclusion Criteria:

• Pathological examination diagnosed as HER2-positive breast cancer (HER2-positive definition: standard immune Histochemistry (IHC) test is 3+ or ISH test is positive).
• Local or regional recurrence of breast malignant tumors.
• The clinical stage of the tumor is stage IV (metastatic) breast cancer.
• Bilateral breast cancer (including contralateral carcinoma in situ).
• History of serious lung diseases such as interstitial pneumonia.
• Have received CDK4/6 inhibitor treatment or other anti-tumor biological treatments in the past therapy, targeted therapy or tumor immunotherapy.
• Have undergone major surgical operations, any investigational drugs, or others within 4 weeks before randomization Anticancer treatment or use of immunomodulators (excluding surgery, chemotherapy, radiotherapy and endocrine therapy).
• The presence of other serious physical or mental illnesses or laboratory abnormalities that may increase participation The risks of the research, or interference with the research results, and the researcher's opinion that he is not suitable to participate in this research study patients.