Radiation OmisSion in PAtients With CLinically Node Negative Breast Cancer Undergoing Lumpectomy

Study Overview
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Brief Summary
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To de-escalate radiation therapy in women with breast cancer.

Detailed Description
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The study is a prospective, multi-center, single arm cohort study of omission of adjuvant whole breast radiation therapy (WBRT) following breast conserving surgery (BCS) in patients with a pathological complete response (pCR) following neoadjuvant chemotherapy (NAC). Eligible and consenting female patients with newly diagnosed T1-3 node negative breast cancer with no clinical evidence of distant metastatic disease, who have been treated with NAC, BCS and axillary staging surgery with final pathology demonstrating a pCR (ypT0N0) will be enrolled to the study and followed. The first analysis is planned when follow-up is a median of 5 years. Study participants will not receive adjuvant WBRT, the current standard of care. The primary outcome is ipsilateral breast tumour recurrence (IBTR) at median 5-year follow-up. Study participants will be followed and assessed for local recurrence, regional recurrence, distant recurrence, DFS and OS. In addition, any additional breast cancer treatments received by the participant for the first recurrence event including repeat BCS, mastectomy, additional systemic therapy and radiation therapy (RT) will be documented. The planned sample size is 352 study participants.

Official Title
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Radiation OmisSion in PAtients With CLinically Node Negative Breast Cancer Undergoing Lumpectomy and With a PathologIc Complete REsponse After Neoadjuvant Chemotherapy

Conditions
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Breast Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patient with a new histological diagnosis of clinical T1-3 N0 breast cancer (any tumour sub-type). Negative lymph node involvement at initial presentation, documented by imaging (US or MRI), fine needle aspiration (FNA) or core needle biopsy. Treated with a minimum of 8 weeks NAC, with patients with Her2+ disease receiving targeted anti-Her2+ therapy. Marker clip placed in the tumour bed prior to or during neoadjuvant chemotherapy when the tumour can still be identified. Treated by BCS with complete excision of the tumour bed and axillary staging surgery (either sentinel lymph node biopsy or axillary lymph node dissection). Final pathology demonstrating a pCR [defined as absence of residual invasive and in-situ breast cancer within the breast or lymph nodes (ypT0N0)]. Exclusion Criteria: Age less than 50 years. Inflammatory breast cancer or breast cancer invading the skin or chest wall (T4 disease). Multicentric disease (i.e., breast cancer involving more than one quadrant in the same breast). Prior history of ipsilateral or contralateral in-situ or invasive breast cancer. Patients with a history of lobular carcinoma in-situ (LCIS) are ineligible. Synchronous contralateral in-situ or invasive breast cancer. BRCA (breast cancer gene) 1 or 2 genetic mutation carrier, or other genetic mutation present associated with increased risk of breast cancer. Other previous non-breast malignancies except adequately treated non-melanoma skin cancers, in situ cancers or other cancers curatively treated with no evidence of disease for ≥ 5 years. Inability to complete entire course of neoadjuvant therapy (minimum of 8 weeks of treatment). Patients with HR+ (hormone receptor) disease who are not planned to have endocrine therapy initiated. Patients with Her2+ disease who have not received or are not planned to receive Her2 targeted therapy. ECOG (Eastern Cooperative Oncology Group) performance status > 3. Inability to provide informed consent.

Ages Eligible for Study
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Minimum Age: 50 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Single Arm Cohort<br>The study population consists of women with newly diagnosed T1-3 node negative breast cancer with no clinical evidence of distant metastatic disease, that have been treated with NAC, BCS and axillary staging surgery with final pathology demonstrating a pCR (defined as absence of residual invasive and in situ breast cancer within the breast or lymph nodes). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ipsilateral breast tumour recurrence (IBTR) | defined as ipsilateral recurrence (invasive or insitu) in the ipsilateral breast or chest wall. Histological evidence of IBTR is required. All such events will be reviewed by a central adjudication committee. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mastectomy free interval | defined as time from registration to undergoing ipsilateral mastectomy. | 5 years | 
| Relapse free interval (RFI) | defined as time from registration to recurrence of invasive disease in the ipsilateral breast, regional nodes (axilla, supraclavicular, or internal mammary), distant areas beyond local or regional limits (distant recurrence), and death from breast cancer. | 5 years | 
| Disease free survival (DFS) | defined as time from registration to in breast invasive tumour recurrence, regional invasive recurrence, distant recurrence, contralateral breast cancer, second primary non-breast cancers, death from breast cancer, and death from non-breast cancer. | 5 years | 
| Overall survival (OS) | defined as time from registration to death from any cause. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinically node negative breast cancer, Ipsilateral breast tumour recurrence, Neoadjuvant chemotherapy