Trial Evaluating Role of Post Mastectomy Radiotherapy in Women With Node Negative Early Breast Cancer

Study Overview
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Brief Summary
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Postmastectomy radiotherapy (PMRT) is unequivocally beneficial in reducing the recurrences as well as improving survival in node positive breast cancer patients. PMRT for women with T1-T2 tumors and negative axillary nodes is not generally warranted because of the presumed low risk of recurrence in this population as a whole. However, in the setting of multiple adverse prognostic factors, the recurrence risk approaches and in some cases surpasses the risk of recurrence documented for patients with one to three positive lymph nodes. Numerous retrospective series have reported the outcome and patterns of failure for post-mastectomy patients treated without radiation. Many of these series have analyzed several high risk factors which were predictive of loco-regional recurrence wherein the role of adjuvant post-mastectomy radiation can be considered. Some authors have used combinations of prognostic factors, such as age, tumour size, grade, receptor status, Her2neu status and lympho-vascular space invasion to define subgroups with more specific risks of loco-regional recurrence than single factors alone. The current trial hypothesizes that Post-mastectomy radiation in high risk, node negative early breast cancer patients decreases rates of loco-regional recurrence and improves disease free survival and propose to address the question in randomized setting.

Official Title
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Post-Mastectomy Radiation Therapy in High Risk, Node Negative Women With Early Breast Cancer (PMRT-NNBC)

Conditions
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Breastcancer

Intervention / Treatment
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* Radiation: Post Mastectomy Radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with unilateral pT1,2N0M0 breast cancer or multifocal breast cancer if largest discrete tumour at least 2cm or if the tumour area comprises multiple small adjacent foci of invasive carcinoma then overall maximum dimension taken. This must be greater than 2cm. Upfront total mastectomy (with minimum 1 mm margin clear of invasive cancer or DCIS) and axillary staging procedure (clearance, sampling or SNB) T2 tumors with one risk factor or T1 tumors with any of the following two high risk factors such as presence of high grade, lymphovascular invasion, ER/PR negative, HER2 positivity, age < 35 years. Fit to receive adjuvant radiation +/- chemotherapy (if indicated) +/- hormonal therapy (if indicated) Written, informed consent Exclusion Criteria: Any pTis/3/4, M1 patients Patients who have any pathologically involved axillary nodes (micro-metastasis may be allowed) Patients who have undergone neoadjuvant systemic therapy. Previous or concurrent malignancy other than non melanomatous skin cancer and carcinoma in situ of the cervix Pregnancy Bilateral breast cancer Not fit for surgery, radiotherapy or adjuvant systemic therapy Unable or unwilling to give informed consent

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Arm Experimental Post Mastectomy Radiotherapy Arm No Intervention: No Post Mastectomy Radiotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Post Mastectomy Radiation Therapy (PMRT)<br>Post mastectomy radiotherapy will be given | Radiation: Post Mastectomy Radiation therapy<br>* Post mastectomy radiotherapy to the chest wall and ipsilateral supra-clavicular fossa to a dose of 40 Gy in 15 fractions over 3 weeks<br>* Other names: PMRT;|
| No Intervention: Observation (No PMRT)<br>No adjuvant radiotherapy will be given. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | This will be measured using Kaplan Meier time to event analysis | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chest wall recurrence | This is the incidence of local recurrence in the chest wall | 5 years | 
| Regional recurrence | This is the incidence of recurrence in the regional lymphatics | 5 years | 
| Metastasis-free survival | This will be measured using Kaplan Meier time to event analysis | 5 years | 
| Overall survival | This will be measured using Kaplan Meier time to event analysis | 5 years | 
| Acute Morbidity of radiotherapy | RTOG Acute radiation morbidity scoring | 4 weeks from the start of radiotherapy | 
| Late Morbidity of radiotherapy | RTOG Late radiation morbidity scoring | 6 months from end of radiotherapy to 5 years | 
| Quality of life scores under different domains of the QLQ C-30 and BR-23 questionnaires | Quality of life will be assesses by EORTC QLQ C-30 core questionnaire and the breast cancer specific module BR-23 questionnaire | 5 years post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-Mastectomy Radiation, Node Negative, Early breast Cancer