RANDOMIZED OPEN-LABEL, MULTICENTRIC, PHASE II CLINICAL TRIAL TO EVALUATE THE EFFICACY OF A NEOADJUVANT CHEMOTHERAPY SCHEME CUSTOMIZED BY LEVELS OF BRCA1 AND ERCC1 IN WOMEN WITH PRIMARY HER2 NEGATIVE BREAST CANCER

INTERVENTION: Product Name: Cyclophosphamide Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: CYCLOPHOSPHAMIDE CAS Number: 50‐18‐0 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 600‐ Product Name: Docetaxel Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: DOCETAXEL CAS Number: 114977‐28‐5 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 75‐ Product Name: Fluorouracil Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: FLUOROURACIL CAS Number: 51‐21‐8 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 200‐ Product Name: Cisplatin Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: CISPLATIN CAS Number: 15663‐27‐1 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 60‐ Product Name: Epirubicin Pharmaceutical Form: Concentrate for solution for injection/infusion INN or Proposed INN: EPIRUBICIN CAS Number: 56420‐45‐2 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 60‐ Product Name: Palitaxel Pharmaceutical Form: Concentrate for solution for injection/infusion INN or Proposed INN: PACLITAXEL CAS Number: 33069‐62‐4 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 100‐ Product Name: Cyclophosphamide Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: CYCLOPHOSPHAMIDE CAS Number: 50‐18‐0 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 600‐ Product Name: Epirubicin Pharmaceutical Form: Concentrate for solution for injection/infusion INN or Proposed INN: EPIRUBICIN CAS Number: 56420‐45‐2 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 90‐ Product Name CONDITION: Primary breast cancer, ER or PgR positive, or triple negative and HER‐2 negative, larger than 2 cm in diameter. ; MedDRA version: 14.1 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 14.1 Level: LLT Classification code 10069196 Term: Cytostatic chemotherapy System Organ Class: 100000004865 Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] ‐ Therapeutic techniques [E02] PRIMARY OUTCOME: Main Objective: To evaluate and compare the rate of complete response or pCR (according NSABP guidelines) at the time of surgery in patients with luminal A o B and triple negative (non‐Her2/Erb 2 overexpressing and/or amplified) operable breast cancer randomized to standard neoadyuvant chemotherapy (NAC) based in antracyclines versus customized NAC according levels of BRCA1 and ERCC1 mRNA (measured by quantitative RT‐PCR). Primary end point(s): Pathological Complete Response (pCR) is the primary endpoint. ; Surgical breast and axillary node resection specimens will be evaluated for pathologic tumour response according to NSABP guidelines. Patients will be considered in pCR if there is no invasive cancer in the breast or only non‐invasive in situ cancer in the breast specimen. Secondary Objective: To compare the objective response rate (partial plus complete) among the two arms at definitive surgery.; To compare the percent of patients with node‐negative disease at surgery among the two treatments arms.; To compare the rate of conversion to breast conserving surgery among the two treatments arms.; To compare the rate of conversion to breast surgery of patients with non‐operable breast cancer among the two arms. ; To compare disease free survival (DFS) and overall survival (OS).; To identify the molecular characteristics of responding tumors by inmunohistochemical, FISH genomic and proteomic analysis. Timepoint(s) of evaluation of this end point: Tumour pCR will be assessed at baseline and after definitive surgery. SECONDARY OUTCOME: Secondary end point(s): Feasibility and type of surgery as indicated by surgeon prior to study treatment. It will be recorded for each patient enrolled at baseline as well as after neoadjuvant treatment period. ; Percentage of patients with negative axillary nodes at the time of definitive surgery, in both treatment arms.; Complete and partial tumor response at the time of surgery. Tumoral response will be assessed by clinical examination and by breast tumor imaging with mammography, ultrasound or MRI, according to the facilities at each site.Overall response (OR) will be assessed using the WHO criteria. ; Disease free survival (DFS), defined as the time from definitive surgery until disease recurrence. ; Overall survival (OS), defined as the time from completion of surgery to death from any cause.; Identification of molecular characteristics of tumors that are sensitive to therapy, using immunohistochemical analysis of tumor samples (biopsies and resection), as well as in‐situ fluorescent hybridization techniques (FISH) in genomics and proteomics. Timepoint(s) of evaluation of this end point: Each secondary endpoint will be evaluated according to the timepoints set out in the protocol. INCLUSION CRITERIA: Female gender Age ? 18 years Performance Status‐ ECOG: 0‐1 Histologically confirmed invasive breast cancer Primary tumor greater than 2 cm diameter Any N (0‐3) No evidence of metastasis (M0), HER‐2/ERBb2 negative. Known hormone receptors status. Haematopoietic status: Absolute neutrophil count ? 1.5 x 109/L; Platelet count ? 100 x 109/L; Hemoglobin at least 9 g/dl) Hepatic status: Serum total bilirubin ? 1.5 x upper limit of normal (ULN), in the case of known Gilbert?s syndrome, a higher serum total bilirubin (< 2 x ULN) is allowed;AST and ALT ? 2.5 times ULN; Alkaline phosphatase ? 2.5 times ULN) Renal status: Creatinine ? 1.5 mg