HR+/HER2- Breast Cancer
Conditions
Keywords
Breast Cancer, Radiotherapy, Immunotherapy
Brief summary
This study is a prospective, randomized controlled clinical trial designed to evaluate the efficacy and safety of combining radiotherapy, chemotherapy, and immunotherapy in the neoadjuvant treatment of high-risk HR+/HER2- breast cancer patients. The study plans to enroll treatment-naïve HR+/HER2- breast cancer patients aged 18-75 with high-risk features (e.g., tumor size ≥3 cm or lymph node positivity, Ki-67 ≥20%). Eligible subjects will be randomized in a 1:1 ratio into two groups: the control group will receive neoadjuvant chemotherapy (nab-paclitaxel followed by epirubicin + cyclophosphamide) in combination with sintilimab immunotherapy; the experimental group will receive the same chemotherapy and immunotherapy regimen with the addition of stereotactic body radiotherapy (SBRT) administered early during treatment, at a prescribed dose of 8 Gy per fraction for 3 fractions, with one fraction per day. The study has dual primary endpoints: pathological complete response (pCR,) and objective response rate (ORR ). Secondary endpoints include 3-year event-free survival (EFS), incidence of adverse events (CTCAE v5.0), and postoperative cosmetic outcomes of the breast. The study design incorporates hierarchical testing to control for multiplicity, and long-term follow-up is planned to evaluate survival benefits. The study has been approved by the ethics committee, and all participants are required to provide written informed consent. The results are expected to offer a novel neoadjuvant treatment strategy for high-risk HR+/HER2- breast cancer patients and improve their therapeutic outcomes.
Interventions
RADIATIONNeoadjuvant radiotherapy
Neoadjuvant Radiotherapy Regimen: 1. Radiotherapy Technique: Stereotactic Body Radiation Therapy (SBRT) Radiation Dose and Fractionation: 8 Gy per fraction, for a total of 3 fractions, amounting to a total dose of 24 Gy 2. Radiotherapy Schedule: Irradiation begins on the second day of the first chemotherapy cycle and is administered every other day 3. Target Volume Definition: The radiotherapy target volume is defined based on baseline imaging (e.g., CT, MRI, or PET-CT) 4. Radiotherapy Equipment and Planning: Treatment is delivered using a linear accelerator equipped with Image-Guided Radiotherapy (IGRT) technology to ensure precise irradiation and dose optimization
Neoadjuvant Chemotherapy Regimen: A sequential chemotherapy strategy is adopted, with the specific regimen as follows: Taxane-based Chemotherapy Phase (T Phase): Nab-paclitaxel (125 mg/m²), administered by intravenous infusion on Day 1 and Day 8 of each 21-day cycle (Q3W), for a total of 4 cycles. Anthracycline-based Combination Chemotherapy Phase (EC Phase): Epirubicin (75-100 mg/m²) in combination with cyclophosphamide (600 mg/m²), administered by intravenous infusion every 21 days (Q3W), for a total of 4 cycles. The EC phase commences upon completion of the T phase.
Immunotherapy Regimen: Sintilimab (200 mg), administered by intravenous infusion every three weeks (Q3W). Dosing begins on Day 2 of the chemotherapy cycles, for a total of 8 treatment cycles.
Sponsors
First Affiliated Hospital of Wenzhou Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Newly diagnosed, untreated breast cancer; 2. Age: 18 years ≤ age ≤ 75 years; 3. Histologically confirmed hormone receptor-positive (HR+) tumor specimen (estrogen receptor \[ER\] ≥ 10%); 4. Human epidermal growth factor receptor-2 immunohistochemistry (HER2-IHC) result of 0/1+ or 2+ with negative fluorescence in situ hybridization (FISH) test; 5. Histologically confirmed cell proliferation index (Ki67) ≥ 20%; 6. Programmed death-ligand 1 combined positive score (PD-L1 CPS) evaluable (i.e., availability of fresh/archived specimens); 7. Good pulmonary function; 8. Adequate hepatic and renal function; 9. Histological grade ≥ 2; 10. cN0, cT ≥ 3 cm or cN1-3, cT ≥ 2 cm (cT: clinically assessed maximum diameter of primary tumor; cN: clinically assessed regional lymph node status); 11. Eastern Cooperative Oncology Group Performance Status (ECOG score) 0-1.
Exclusion criteria
1.Pregnancy; 2.Tumor \> 8 cm with skin ulceration; 3.History of thoracic radiotherapy or contraindications to radiotherapy; 4.Active autoimmune disease; 5.Prior use of PD-L1 antibody therapy; 6.De novo breast cancer; 7.There are factors that may significantly increase the risk of lung or cardiac toxicity related to radiotherapy, such as (1) maximum lung depth(MLD) \>3.2cm； (2) maximum heart distance(MHD) \<2.4cm。
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response rate（pCR） | Pathological diagnosis results were obtained tithin one month after the operation | Postoperative pathological assessment (tumor Miller-Payne system grading and axillary lymph node pathological assessment) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate(ORR) | At the end of Cycle 8 (each cycle is 28 days) | The proportion of patients achieving complete response (CR) and partial response (PR) after tumor treatment was used as the second endpoint of the primary endpoint for hierarchical testing. |
| Event-free survival rate | Long-term follow-up monitoring was conducted until 3 years after enrollment | The time from randomization to the event (recurrence, metastasis or death) |
| Incidence of adverse reactions | 1 year | Continuous monitoring, assessment and patient feedback. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The breast-conserving rate of breast malignant tumor surgery | Perioperative/Periprocedural | The breast-conserving rate of breast malignant tumor surgery |
Countries
China
Outcome results
None listed