Prognostic Value of Estrogen Receptor and Ki-67 Index after Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Expressing High Levels of Proliferation at Diagnosis

Abstract

Purpose: Breast cancers expressing high levels of Ki-67, a nuclear marker of cell proliferation, are associated with worse outcome. Recent data from neoadjuvant studies indicate that a single measurement of the nuclear proliferation marker Ki-67 in breast carcinoma during neoadjuvant therapy is strongly predictive of long-term outcome. Secondly, recent literature data indicate that prognostic evaluation with Ki-67 may be better after pre-surgical therapy. A retrospective study from a prospectively maintained clinical database to compare the predictive and prognostic significance of biological markers, assessed before and after neoadjuvant chemotherapy, in locally advanced breast cancer, was performed. Patients and Methods: The following parameters were considered before and after chemotherapy for their relationship with treatment response and disease-free survival in 64 patients with locally advanced breast cancer: clinical stage, clinical and pathological lymph node involvement, Ki-67, estrogen receptor (ER), progesterone receptor (Pgr), Her2, tumor grade, clinical response, type of surgery performed, and number of chemotherapy cycles administered. The expression of Ki-67 was assessed using immunohistochemistry in pre-therapy tru-cut and post-therapy surgical excision specimens after neoadjuvant chemotherapy; only patients with breast tumors expressing high baseline Ki-67 (≧15%) were included in the analysis. In addition, the correlation between pre-chemotherapy biological markers and clinical and pathological response was reported. Results: Post-chemotherapy Ki-67 proliferation index decrease, pre-chemotherapy ER expression and post-chemotherapy ER expression were the only significant prognostic factors adversely influencing disease-free survival in univariate analysis. Her2 overexpression was the only factor to impact on the clinical response. Conclusions: Post-treatment Ki-67 and ER status were predictors of outcome for patients with locally advanced breast cancer and a high pre-chemotherapy proliferation index.