A Dose Escalation Study of Proton and Carbon Ion Irradiation for HER2 Positive and Triple Negative Breast Cancer

Study Overview
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Brief Summary
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Adjuvant radiotherapy is the standard treatment for early breast cancer after breast conserving surgery. Molecular subtypes was significantly associated with the risk of local recurrence of breast cancer. Nguyen et al found that the overall 5-year cumulative incidence of local recurrence was 0.8% for luminal A, 1.5% for luminal B, 8.4% for HER2 positive, and 7.1% for triple negative breast cancer after lumpectomy and radiotherapy. Her2 positive and triple negative breast cancers may be inherently radioresistant. Therefore, for HER2 positive and triple negative breast cancer with high local recurrence and radiation resistance, proton combined with carbon ion is proposed after breast conserving surgery.

Official Title
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A Dose Escalation Study of Proton and Carbon Ion Irradiation for HER2 Positive and Triple Negative Breast Cancer After Breast Conserving Surgery

Conditions
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Triple Negative Breast Cancer, HER2-positive Breast Cancer

Intervention / Treatment
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* Radiation: proton plus carbon ion radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed HER2 positive or Triple Negative invasive breast carcinoma.(HER2 positive: immunohistochemistry [IHC] 3+ and or fluorescence in situ hybridization [FISH] amplified; Triple Negative: estrogen receptor [ER] and progesterone receptor [PR] < 1%, HER2 negative [IHC 1+ or 2+ FISH non-amplified]) Age ≥ 18 years and ≤ 80 years. The primary tumor must be excised via breast conserving surgery. Stage p T1-2 N0 M0 ECOG performance status ≤2. Exclusion Criteria: Invasive breast cancer not confirmed by pathology. Distant metastasis Prior thoracic radiation. Pregnancy or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: proton plus carbon ion radiotherapy<br>CTV1: whole breast, proton therapy. CTVboost: Tumor bed, carbon ion dose escalation study with four dose levels. | Radiation: proton plus carbon ion radiotherapy<br>* CTV1: whole breast, 40.05Gy(RBE) in 15 fractions with proton ion therapy; CTVboost: Tumor bed, carbon ion dose escalation study with four dose levels [10.2Gy(RBE)/3Fx,10.8Gy(RBE) /3Fx,11.4Gy(RBE)/3Fx and 12Gy(RBE)/3Fx ].<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute toxicity | Treatment related acute toxicity assessed by CTCAE v4.03 | 3 months after the completion of CIRT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local regional recurrence | The Ipsilateral breast and regional lymph nodes recurrence | within 5 years after radiotherapy. | 
| Cosmetic outcome as measured by Breast Cancer Treatment Outcomes Scale | Cosmetic outcome will be evaluated by Breast Cancer Treatment Outcomes Scale filled out by patients. | within 5 years after radiotherapy. | 
| Cosmetic outcome as measured by BCCT.core software | Patients' photographs of the breasts will be taken. With the use of BCCT.core software from The Breast Research group (INESC TEC) cosmetic outcome will be assessed. | within 5 years after radiotherapy. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, HER2 Positive, Triple Negative, Proton and Carbon Ion, Dose Escalation