Trial With Autologous Dendritic Cell Vaccination in Patients With Stage II-III HER2 Negative Breast Cancer

• Number of participants with adverse events [ Time Frame: During the 6-24 months of administration of the vaccine ] [ Designated as safety issue: Yes ]
• Impact of the vaccine on patients DFS and OS [ Time Frame: three to five years after the diagnosis of breast cancer ] [ Designated as safety issue: Yes ]
  We will compare our cohort of patients vaccinated and treated with chemotherapy, surgery and radiation therapy with an historic cohort in our center treated with the same schedule of chemotherapy , surgery and radiation therapy without the vaccine
• EORTC quality of life [ Time Frame: From 9 months and up to two years ] [ Designated as safety issue: Yes ]
• Correlation among the specific immune response induced in patients and the pathologic response of the tumor [ Time Frame: 6-24 months ] [ Designated as safety issue: No ]
  Specific immune response will be evaluated as delayed hipesrsensitivity (DTH), humoral response by cuantification antibodies against tumoral cells (ELISA)and cellullar response (proliferation assay and citokines production)

Molecular expression in breast cancer (BC) defines special fenotypes with different prognostic and predictive features.Since the addition of trastuzumab and lapatinib to chemotherapy, HER2 overexpressing tumors have become the best responders to systemic therapies, reaching pathologic complete response rates (pCR) around 50%. But HER2 negative tumors (luminal A and triple negative) are characterized by low chemosensitivity (luminal A) or early distant relapse after diagnosis (triple negative BC) . In this open, prospective, non-randomized and multicentric phase II study the investigators include stage II and III HER2 negative BC patients that are going to receive neoadjuvant sequential chemotherapy Epirubicin+Ciclofosfamide x 4 and then Docetaxel x 4)with an individualized vaccination with autologous dendritic cells pulsed with their own tumor. The hypothesis is that the reinforcement of the immune system with the autologous dendritic cell vaccination against HER2 negative BC could increase pathologic complete responses (pCR) and disease free survival(DFS), when added to chemo, surgery and radiation therapy and in a maintenance schedule.

Chemotherapy schedule:

• dose dense epirubucin 100 mgr/m2 plus ciclofosfamide 600 mgr/m2 every two weeks for four cycles with with GM-CSF support on day +1 (pegylated filgastrim) or on days +5 to +9 (filgastrim) subcutaneously
• docetaxel 80-100 mgr/m2 every three weeks for four cycles. Addition of GM-CSF if docetaxel doses are > 85 mgr/m2

• Stage II Breast Cancer
• Stage III Breast Cancer

Inclusion Criteria:

• HER2 negative and stage II and III Breast cancer patients who benefit with neoadjuvant chemotherapy
• age 18-75
• to get enough tumoral sample to elaborate the vaccine

Exclusion Criteria:

• pregnancy
• severe diseases
• hepatitis or HIV
• need to be on immunosuppressant drugs

• CAIBER (Spanish Clinical Research Network)
• Ministerio de Sanidad de España (Spanish Institute of Health)