Breast cancer is a heterogeneous disease with different clinical behavior. The molecular classification of breast cancer differentiates, at least, three subgroups of tumors: the luminal subtype with cells expressing estrogen receptors and ER-related genes; the human epidermal growth factor receptor 2 (HER2)-overexpressing subtype; and the basal-like subtype associated with the expression of basal cell markers. Targeted therapies for TNBC are not completely validated and the main treatment for this group of tumors is the use of chemotherapy, including platinum as single agent or in combination with other chemotherapy agents.
From June 2010 to November 2011, 149 locally advanced triple negative breast cancer patients in the oncology department, Tanta University, were assigned to receive four cycles of PCb with dose of paclitaxel 80 mg/m2 and carboplatin AUC 2, given day 1, 8 and 15 of every 4 weeks. Immunohistochemistry of the following molecular markers: the estrogen receptor, progesterone receptor, HER2, p53, and Ki67. For ERCC1, grading was (0: no expression, 1: weak expression, 2: moderate expression, 3: strong expression). Operable disease should be subjected to surgery within 4 weeks from the last chemotherapy cycle. An additional two cycles of weekly PCb were delivered after surgery in patients who achieved pCR. Four cycles PCb could be administrated after surgery in patients showing response at pathologic assessment.
Ninety patients (60.4%) showed negative ERCC1 expression. Negative ERCC1 expression was associated with higher pathological CR (71.1%) than positive ERCC1 (15.3%) to PCB (P = 0.001). Five year OS was better in negative ERCC1 versus positive ERCC1 (92.1 % versus 51.4% respectively, p value 0.001). Five year DFS was better in negative ERCC1 versus positive ERCC1 (69,6 % versus 64.2% respectively, p value 0.001). In multivariate analysis ERCC1 maintained statistical siginficance as regard OS & DFS.
In conclusion, the expression of this ERCC1 protein is lower in TNBC and associated with high pathologic complete response to carboplatin-taxol with better overall survival and DFS. ERCC1 and other pathological markers may be used to define better treatment lines for locally advanced triple negative breast cancer.
Clinical trial identification
Legal entity responsible for the study
Tanta University Hospital, Oncology Department
The authors of the study
All authors have declared no conflicts of interest.