Research article

Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy

Kyung-Hun Lee¹ , Seock-Ah Im^1,5 , Do-Youn Oh^1,5 , Se-Hoon Lee^1,5 , Eui Kyu Chie² , Wonshik Han^3,5 , Dong-Wan Kim^1,5 , Tae-You Kim^1,5 , In Ae Park⁴ , Dong-Young Noh^3,5 , Dae Seog Heo^1,5 , Sung Whan Ha² and Yung-Jue Bang^1,5

¹  Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

²  Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea

³  Department of General Surgery, Seoul National University College of Medicine, Seoul, Korea

⁴  Department of Pathology, Seoul National University College of Medicine, Seoul, Korea

⁵  Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

author email corresponding author email

BMC Cancer 2007, 7:63doi:10.1186/1471-2407-7-63

Published:	12 April 2007

Abstract

Background

Bcl-2 is positively regulated by hormonal receptor pathways in breast cancer. A study was conducted to assess the prognostic significances of clinico-pathologic variables and of ER, PR, p53, c-erbB2, bcl-2, or Ki-67 as markers of relapse in breast cancer patients who had received the identical adjuvant therapy at a single institution.

Methods

A cohort of 151 curatively resected stage III breast cancer patients (M:F = 3:148, median age 46 years) who had 4 or more positive lymph nodes and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinico-pathologic characteristics including disease-free survival (DFS) and overall survival (OS). Patients with positive ER and/or PR expression received 5 years of tamoxifen following AC/T. The protein expressions of biomarkers were assessed immunohistochemically.

Results

The median follow-up duration was 36 months, and 37 patients (24.5%) experienced a recurrence. Univariate analyses indicated that the tumor size (P = 0.038) and the number of involved lymph nodes (P < 0.001) significantly affected the recurrences. However, the type of surgery, the histology, histologic grade, the presence of endolymphatic emboli, and a close resection margin did not. Moreover, ER positivity (P = 0.013), bcl-2 positivity (P = 0.002) and low p53 expression (P = 0.032) were found to be significantly associated with a prolonged DFS. Furthermore, multivariate analysis identified 10 or more involved lymph nodes (HR 7.366; P < 0.001), negative bcl-2 expression (HR 2.895; P = 0.030), and c-erbB2 over-expression (HR 3.535; P = 0.001) as independent indicators of poorer DFS. In addition, bcl-2 expression was found to be significantly correlated with the expressions of ER and PR, and inversely correlated with the expressions of p53, c-erbB2 and Ki-67. Patients with bcl-2 expression had a significantly longer DFS than those without, even in the ER (+) subgroup. Moreover, OS was significantly affected by ER, bcl-2 and c-erbB2.

Conclusion

Bcl-2 is an independent prognostic factor of DFS in curatively resected stage III breast cancer patients and appears to be a useful prognostic factor in combination with c-erbB2 and the number of involved lymph nodes.