Tumor Suppressor Status as a Predictor of Chemotherapy Response in Triple Negative Breast Cancer

Study Overview
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Brief Summary
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This is a prospective observational study aimed to validate biomarkers that predict response.

Detailed Description
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This is a prospective observational cohort study, with no control group and no direct experimental intervention, where the patient's pathological material will be used to examine the expression of molecular biomarkers believed to predict chemotherapy response. Patients with locally advanced triple negative breast cancer, who are candidates for neoadjuvant chemotherapy, will be enrolled in this clinical study. Patients will receive standard of care, FDA-approved and clinically validated chemotherapy regimens. The biopsy specimens taken during the diagnostic phase (pre-treatment specimen) will be used for specific biomarker evaluation. Data obtained from this pre-treatment phase will be compared with the surgical specimens (post-treatment phase) obtained after receiving neoadjuvant chemotherapy. The primary endpoint is to assess the ability of specific biomarkers to predict treatment response, and thus identify those patients who will achieve benefit from such treatment.

Official Title
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Tumor Suppressor Status as a Predictor of Chemotherapy Response in Triple Negative Breast Cancer.

Conditions
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Breast Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years old Histologically-confirmed triple negative invasive breast carcinoma Any type of ductal or lobular invasive carcinoma Patients with or without BRCA-1 and BRCA-2 mutations are eligible to participate Life expectancy > 6 months Pre-, Peri- or Postmenopausal Clinical Stage T2-4, N0-3, M0 (Stage II-III) Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial Adequate hematologic, renal, and liver function and functional status that permit chemotherapy administration. However, these parameters will be evaluated by the treating physician, and decisions regarding eligibility for chemotherapy or surgery will be made on a case by case scenario. Exclusion Criteria: Prior history of and/or active therapy for invasive breast cancer (includes chemotherapy, radiation, hormonal therapy including AIs, tamoxifen, raloxifene, fulvestrant or any other antiestrogen/SERM) Patients with a currently active second malignancy other than non-melanoma skin cancers are not to be registered. Patients are not considered to have a currently active malignancy if they have completed therapy and are now considered to be at less than 30% risk for relapse (by their physician). Only ductal/lobular carcinoma in situ but not invasive component Any sort of confirmed metastatic disease (AJCC Stage IV at diagnosis) Any sort of active local radiation therapy (to the breast or the axilla), before the neoadjuvant chemotherapy Pregnant or lactating, in case this precludes the subject to receive chemotherapy. Impossibility to receive neoadjuvant chemotherapy due to significant medical comorbidities, allergies or performance status. This will be exclusively decided by the treating oncologists.

Ages Eligible for Study
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Minimum Age: 18 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological status of retinoblastoma tumour suppressor (RB) | The primary endpoint is to assess the impact of histological RB-status on pathological complete response (pCR). pCR is a well validated surrogate of chemotherapy sensitivity and allows the identification of a group of patients with excellent prognosis. | Nine weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of RB and other biomarkers | Correlation between RB and PTEN tumor suppressor status and other biomarkers with pCR Correlation between RB-status, RB and PTEN status and other biomarkers with recurrence free survival (RFS) and overall survival (OS) | Nine weeks | 
| Determine the utility of an RB molecular test | Gene expression profiling of biopsy specimens to determine utility of an RB molecular test. | Assessed within 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RB, Triple negative Breast Cancer, PTEN, Chemotherapy, Neoadjuvant