Use of INnovative and Micro-INvasive TEchniques for the Early Identification of Breast Cancer Patients Benefitting From Neo-adjuvant Therapy

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is the identification of novel micro-invasive predictors of pathological complete response (pCR) during neo-adjuvant therapy

Detailed Description
-----------------
This is a single arm prospective, monocentric, open, experimental pilot study. The response to NAC in breast cancer is extremely heterogeneous. The study and the identification of factors that can predict the response to treatment is therefore a priority, constituting a relevant clinical unmet need.Modern molecular biology techniques as well as imaging diagnostics could be valuable tools for characterizing the response to NAC toward the definition of more personalized therapies.The prediction of therapy response after two cycle of chemotherapy rather than at the end of six cycles using non-invasive procedures will spare unwanted toxicity to the patients and resources to the Regional and National Health system. This study will also provide the patients, their familiar and all the stakeholders involved in the cure of Breast Cancer new important information regarding the management of breast cancer patients.This is a non-interventional study; therefore, the treatment will be as per physician choice according to the most appropriate therapeutic opportunities available for each patients' based on the type and stage of disease and the patients' performance status.Currently, the NAC regimens commonly used at CRO-Aviano for NAC are Epirubicine 90 mg/mq + Ciclophosphamide 600 mg/mq d1 q21 or q14 (EC)(dose dense) followed by weekly Paclitaxel 80 mg/mq for a total of 12 administrations. Occasionally, due to patients and tumor features only weekly Paclitaxel is used, and usually in this case up to 24 administrations may be given. Only in the case of HER2 positive BC trastuzumab 2 mg/kg is added to weekly Paclitaxel. Given the low response rate of hormone-based neoadjuvant therapy, only in rare cases (e.g. patients not amenable of surgery due to comorbidities), this approach is used.

Official Title
-----------------
Use of INnovative and Micro-INvasive TEchniques for the Early Identification of Breast Cancer Patients Benefitting From Neo-adjuvant Therapy

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Diagnostic Test: Liquid biopsy and imaging


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years Histological Diagnosis of Infiltrating Breast Cancer. The presence of measurable mammary lesions; The presence of metabolically active mammary lesions; Performance Status (Eastern Cooperative Oncology Group scale, ECOG) ≤ 1; Compliance with periodic blood withdrawal; Compliance with periodic PET/CT and RMN imaging; Adequate clinical and laboratory test results for undertaking neoadjuvant chemotherapy and surgery; Written informed consent. Exclusion Criteria: The presence of contraindications for the execution of RMN and PET-TC; Presence of metastatic disease; Pre-existing or concurrent tumors, except in situ carcinoma or basophilic carcinoma of the skin; Uncontrolled active infections; Insufficient patient compliance; Absence of signed informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Liquid biopsy and imaging|Liquid biopsy and imaging|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of novel micro-invasive predictors of pathological complete response (pCR) during neo-adjuvant therapy. | 1. Determine if a PET SUV decrease ≥ 50% after two cycles of therapy respect to the basal value will predict the pCR predict the pCR of breast cancer patients treated with neo-adjuvant therapy; | from start of therapy until first documented progression, assessed up to 12 months | 
| Identification of novel micro-invasive predictors of pathological complete response (pCR) during neo-adjuvant therapy. | 2. Determine if a cfDNA variation ≥ 25% of the basal value after two cycles of therapy will predict the pCR of breast cancer patients treated with neo-adjuvant therapy | from start of therapy until first documented progression, assessed up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine if the basal number of CTC and/or its variation after two cycle of therapy will predict the pCR of breast cancer patients treated with neo-adjuvant therapy; | Determine if the basal number of CTC and/or its variation after two cycle of therapy will predict the pCR of breast cancer patients treated with neo-adjuvant therapy; | from start of therapy until first documented progression, assessed up to 12 months | 
| Determine if the basal SERS spectra and/or its variation after two cycle of therapy will predict the pCR of breast cancer patients treated with neo-adjuvant therapy pCR of breast cancer patients treated with neo-adjuvant therapy; | Determine if the basal Metabolomics spectra and/or its variation after two cycle of therapy will predict the pCR of breast cancer patients treated with neo-adjuvant therapy; | from start of therapy until first documented progression, assessed up to 12 months | 
| Determine if the basal SERS spectra and/or its variation after two cycle of therapy will predict the pCR of breast cancer patients treated with neo-adjuvant therapy; | Determine if the basal SERS spectra and/or its variation after two cycle of therapy will predict the pCR of breast cancer patients treated with neo-adjuvant therapy; | from start of therapy until first documented progression, assessed up to 12 months | 
| Determine if the basal Cytokines serum levels and/or their variation after two cycle of therapy will predict the pCR of breast cancer patients treated with neo-adjuvant therapy; | Determine if the basal Cytokines serum levels and/or their variation after two cycle of therapy will predict the pCR of breast cancer patients treated with neo-adjuvant therapy; | from start of therapy until first documented progression, assessed up to 12 months | 
| Determine if a the basal Immune proficiency will predict the pCR of breast cancer patients treated with neo-adjuvant therapy; | Determine if a variation in T cell sub-populations will predict the pCR of breast cancer patients treated with neo-adjuvant therapy; | from start of therapy until first documented progression, assessed up to 12 months | 
| Evaluate over time Relapse Free Survival (RFS) and correlate with micro-invasive parameters from primary and/or secondary objectives. | Evaluate over time Relapse Free Survival (RFS) and correlate with micro-invasive parameters from primary and/or secondary objectives. | from start of therapy until first documented relapse, assessed up to 12 months |