Assessment of Breast Cancer Response to Neoadjuvant Anthracycline-based Chemotherapy by FDG-PET and Molecular Markers

Study Overview
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Brief Summary
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A correlation between early changes in the tumor maximum standardized uptake value (SUVmax) on FDG-PET after one or two cycles of neoadjuvant chemotherapy (NAC) and the pathological response after 6 to 8 cycles has been demonstrated in several independent small series of patients. Breast tumor proliferation status has previously been demonstrated to be a good predictive factor of response to chemotherapy. The best method for assessing proliferation status is unclear. Proportion of cells staining for nuclear Ki67 antigen is the most widely used assay for comparing the proliferation status between tumors. However major variations in analytical procedure and interpretation limited its clinical value. Taking into account the prognosis and predictive value of proliferation gene as a common signature in breast cancer transcriptome analysis, quantitative assessment of mRNA expression of genes involved in proliferation has been developed by the investigators team and others. The evaluation of these parameters is quantitative and reliable and can be standardized for a clinical use. The main objective of the investigators study is to early predict pathological response to anthracycline-based neoadjuvant chemotherapy (NAC) using a combination of parameters based on FDG-PET imaging performed at baseline and after 2 cycles, and molecular markers of proliferation measured on pre-treatment biopsy (Ki67 protein level by immunohistochemistry and Ki67 mRNA level and the mRNA (messenger RNA) expression of the most pertinent genes of the Genomic Grade Index (GGI) component by RT (reverse transcriptase) - qPCR).

Official Title
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Assessment of Breast Cancer Response to Neoadjuvant Anthracycline-based Chemotherapy by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and Molecular Markers

Conditions
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Breast Neoplasms, Breast Cancer

Intervention / Treatment
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* Other: non interventional study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged ≥ 18 years Newly diagnosed invasive breast cancer Stage-II or stage-III Neoadjuvant anthracycline-based chemotherapy Primary breast biopsy must be available Non metastatic, M0 No prior systemic therapy for the presFrance: Direction Generale de la Sante ent tumor Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures Exclusion Criteria: Metastatic breast cancer Uncontrolled diabetes Limited breast cancer immediately accessible to conservative surgery and not candidate for neoadjuvant chemotherapy Previous homolateral breast cancer and/or contralateral breast cancer except if treated by surgery +/- radiation therapy alone without any systemic treatment Any surgery (not including minor procedures such as lymph node biopsy, primary tumor core biopsy, fine needle aspiration) within 12 weeks of start of study treatment; or not fully recovered from any side effects of previous procedures. Diagnosis of any previous malignancy within the last 5 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma, or in situ cervical carcinoma
Sexes Eligible for Study
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All

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 |
| --- | --- |
| main and unique cohort<br> | Other: non interventional study<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response to anthracycline-based neoadjuvant chemotherapy | To analyze separately clinical, pathological and molecular biomarkers currently used to identify molecular breast cancer subgroups of the primary tumor that, coupled with the metabolic response, could improve early pathological prediction. To analyze separately the biological, molecular, and genetic biomarkers from the study that, coupled with the metabolic response, could improve early pathological prediction. To analyze separately high throughput analysis of molecular biomarkers of the primary tumor that, coupled with the metabolic response, could improve early pathological prediction. | Within the first 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 5 years | 
| Overall Survival |  | 3 years | 
| Event Free survival | To determine the 5 years Event free survival (EFS) rates in breast cancer patients according to PET response, biological markers and biomarkers identified with molecular high throughput analysis. | 5 years | 
| Event Free survival | To determine the 3 years Event free survival (EFS) rates in breast cancer patients according to PET response, biological markers and biomarkers identified with molecular high throughput analysis. | 3 years | 
| Breast Cancer specific survival | To determine the 5 years Breast Cancer Specific survival rates in breast cancer patients according to PET response, biological markers and biomarkers identified with molecular high throughput analysis. | 5 years | 
| Breast Cancer specific survival | To determine the 3 years Breast Cancer Specific survival rates in breast cancer patients according to PET response, biological markers and biomarkers identified with molecular high throughput analysis. | 3 years | 
| Pathological partial response to anthracycline-based neoadjuvant chemotherapy | To analyze separately clinical, pathological and molecular biomarkers currently used to identify molecular breast cancer subgroups of the primary tumor that, coupled with the metabolic response, could improve early pathological prediction. To analyze separately the biological, molecular, and genetic biomarkers from the study that, coupled with the metabolic response, could improve early pathological prediction. To analyze separately high throughput analysis of molecular biomarkers of the primary tumor that, coupled with the metabolic response, could improve early pathological prediction. | Within the first 30 days after surgery | 
| Delta SUV | To evaluate the correlation between baseline molecular status of proliferation and FDG uptake measured at baseline, after 2 cycles of NAC and the change (delta SUV). | Within the first 20 days after the second cycle of chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant Therapy, Chemotherapy, Positron-Emission Tomography, PET-CT, FDG, Fluorodeoxyglucose, Diagnosis, Prognosis, Pathological complete response, molecular biology, proliferation genes