Clinical trial NCT02600442: Assessment of Breast Cancer Response to Neoadjuvant Anthracycline-based Chemotherapy by FDG-PET and Molecular Markers
Official title: Assessment of Breast Cancer Response to Neoadjuvant Anthracycline-based Chemotherapy by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and Molecular Markers
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Breast Neoplasms
Breast Cancer
Keywords: Neoadjuvant Therapy
Chemotherapy
Positron-Emission Tomography
PET-CT
FDG
Fluorodeoxyglucose
Diagnosis
Prognosis
Pathological complete response
molecular biology
proliferation genes
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-11-09
Enrollment: 168
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Stage II-III Breast cancer

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).


Eligibility criteria: 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

Primary outcomes:
measure: Pathological complete response to anthracycline-based neoadjuvant chemotherapy
timeFrame: Within the first 30 days after surgery
Secondary outcomes:
measure: Overall Survival
timeFrame: 5 years
measure: Overall Survival
timeFrame: 3 years
measure: Event Free survival
timeFrame: 5 years
measure: Event Free survival
timeFrame: 3 years
measure: Breast Cancer specific survival
timeFrame: 5 years
measure: Breast Cancer specific survival
timeFrame: 3 years
measure: Pathological partial response to anthracycline-based neoadjuvant chemotherapy
timeFrame: Within the first 30 days after surgery
measure: Delta SUV
timeFrame: Within the first 20 days after the second cycle of chemotherapy
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital siant-Louis
Study officials:
affiliation: DRCD
name: Ingrid Veron
role: STUDY_CHAIR
affiliation: APHP, IUH, University Paris Diderot, Paris 7, SPC
name: Patricia de Cremoux, MD-PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: APHP, IUH, University Paris Diderot, Paris 7, SPC
name: David Groheux, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: