Survivin, Ki-67 and tumor grade as predictors of response to docetaxel-based neoadjuvant chemotherapy in locally advanced breast cancer

Abstract

The response rates to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) may vary and the risks may outweigh the benefits in poorly selected patients. This study investigated whether survivin expression, high-level Ki-67 expression, estrogen-receptor (ER) tumor status and high tumor grade are able to predict response to docetaxel-based NAC in LABC patients, in order to perform breast-conserving surgery. In this study, 68 patients (IIb-IIIb) completed 4–6 cycles of TAC (75 mg/m2 docetaxel, 60 mg/m2 pirarubicin and 500 mg/m2 cyclophosphamide, administered every 3 weeks). Tumor samples were obtained prior to chemotherapy. The response to chemotherapy was quantified clinically and pathologically and the histological and molecular tumor characteristics were determined. Association with response was assessed for all the parameters and the patients underwent breast-conserving surgery or radical mastectomy accordingly. A clinical complete response was observed in 21 (31%) and a partial response in 37 (54%) of the 68 patients. Thus, the overall clinical response rate (ORR) was 85%. A pathological complete response (pCR) was observed in 14 (20%) of the 68 patients and 37 patients (54%) underwent breast-conserving surgery. In the univariate analysis, survivin expression, high-level Ki-67 expression and high tumor grade (grade III) were significantly associated with ORR (P=0.007, 0.024 and 0.047, respectively). Survivin expression and high-level Ki-67 expression were significantly associated with pCR (P=0.029 and 0.048, respectively). In the multivariate analysis, survivin expression (P=0.030) and tumor grade (P=0.036), but not high-level Ki-67 and ER expression, were significantly associated with ORR and none of these factors was significantly associated with pCR. In conclusion, expression of survivin and high tumor grade were of predictive value for ORR to docetaxel-based NAC in LABC patients, leading to more patients successfully undergoing breast conserving-surgery. Immunohistochemistry of survivin and the Elston and Ellis criteria of tumor grade may provide a widely applicable, cost-effective method of patient selection for NAC.

Polymorphisms in Survivin (BIRC5 Gene) Are Associated with Age of Onset in Breast Cancer Patients

“…The similar situation is with the association between high survivin expression and Ki67 expression. While some studies [38] showed the same results as here, others showed there was no significant association between survivin and Ki67 [31, 39].…”

Nodal Response to Neoadjuvant Chemotherapy is a Better Predictive Factor of Survival Than Miller-Payne Scoring in Breast Cancer

“…Supporting this hypothesis, findings have suggested that tumors with high histologic grade may predict the pCR in anthracyclinecontaining neoadjuvant therapy. [10][11][12] In the current study, hormone receptor negativity, HER-2neu positivity, and higher grade scores are statistically significant factors that affect pathological complete response development, corroborating previous findings.…”

“…In contrast, several studies could not detect any association between negative ER expression and anthracycline-based chemotherapy response. 11,12 The HER2-neu gene expression was reported to be positive in approximately 30% of breast cancers. 9 Increased expression of HER-2neu is associated with resistance to docetaxel treatment in vitro, also trastuzumab treatment is thought to sensitize breast cancer cells to docetaxel.…”

Fascin expression predicts an aggressive clinical course in patients with advanced breast cancer

“…A number of studies have established molecular markers, which are associated with distinct histopathological features, the response to adjuvant therapy and/or the clinical outcome of breast cancer (2)(3)(4)(5)(6)(7). Furthermore, the following clinicopathological factors are considered to be useful markers for predicting prognosis and identifying therapeutic targets in patients with advanced breast cancer: American Joint Committee on Cancer (AJCC) stage, histological grade, oestrogen receptor (ER) and progesterone receptor (PR) expression, human epithelial growth factor receptor 2 (HER2) amplification, p53 expression and Ki-67 labelling index (2)(3)(4)(5)(6). Based on data obtained from molecular or immunohistochemical (IHC) analyses, breast cancer is classified into four major subtypes: Luminal A, luminal B, basal-like and HER2-positive (7).…”