Breast Cancer, Breast Neoplasms
Conditions
Keywords
Neoadjuvant Therapy, Chemotherapy, Positron-Emission Tomography, PET-CT, FDG, Fluorodeoxyglucose, Diagnosis, Prognosis, Pathological complete response, molecular biology, proliferation genes
Brief summary
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).
Interventions
OTHERnon interventional study
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response to anthracycline-based neoadjuvant chemotherapy | Within the first 30 days after surgery | * 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 5 years | — |
| Event Free survival | 5 years | 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. |
| Breast Cancer specific survival | 5 years | 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. |
| Pathological partial response to anthracycline-based neoadjuvant chemotherapy | Within the first 30 days after surgery | * 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. |
| Delta SUV | Within the first 20 days after the second cycle of chemotherapy | 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). |
Countries
France
Contacts
Primary ContactPatricia de Cremoux, MD-PhD
Backup ContactDavid Groheux, MD-PhD
Outcome results
None listed