Expression of survivin does not appear to influence breast cancer recurrence risk

Abstract

Background: Survivin is an inhibitor of apoptosis, and its expression associates with poor outcomes in multiple cancers. It may be a therapeutic target due to its unique expression in cancer cells. Methods: We estimated the association between nuclear and cytoplasmic survivin expression in primary tumors and breast cancer recurrence. In this case-control study, we included women age 35-69, diagnosed with stage I-III breast cancer between 1985 and 2001, and registered with the Danish Breast Cancer Group. We identified 541 patients with breast cancer recurrence with estrogen receptor-positive disease who were treated with tamoxifen for at least 1 year (ERþ/TAMþ) and 300 with estrogen receptor-negative carcinomas, not treated with tamoxifen, and who survived at least 1 year (ERÀ/TAMÀ). Controls were matched to cases on ER/TAM status, date of surgery, menopausal status, stage and county. Survivin expression was estimated by immunohistochemistry on tissue microarrays. We fit logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associating nuclear and cytoplasmic survivin expression with recurrence. Results: Associations between nuclear and cytoplasmic survivin expression and breast cancer recurrence were near-null in both ERþ/TAM þ and ERÀ/TAM À strata. For the cytoplasmic to nuclear ratio (CNR) of survivin expression, we found a null association in the ERþ/TAM þ group comparing CNR !5 with CNR <5, but an association (OR ¼2.48, 95% CI: 1.15, 5.31) in the ERÀ/TAM À group. Conclusions: Survivin expression was not associated with breast cancer recurrence in this study. The CNR ratio may warrant further investigation especially among ER À tumors.

Role of hypoxia-inducible factor-1α and survivin in breast cancer recurrence and prognosis

“…Additional studies confirm Survivin's association with high tumor grade cancers and recurrence [ 23 ]. The present study identified that HIF-1α and survivin were associated with tumor recurrence, which is consistent with ours Recently, Collin conducted two studies on breast cancer in Danish patients and identified that HIF-1α expression in ER-negative tumors was associated with early recurrence in female patients with breast cancer [ 24 ]; however, survivin expression was not associated with breast cancer recurrence, but the ratio of survivin in the cytoplasm to the nucleus may be associated with recurrence [ 25 ]. The results of the present study differ from those of the Danish study.…”

Prognostic Significance of BIRC5/Survivin in Breast Cancer: Results from Three Independent Cohorts

“…Previous studies employed IHC, which allowed visual assessment of BIRC5/survivin protein localization in the cells [ 24 ], but provided no quantitative measures for comparison between samples and the different patient cohorts. Several recent reports presented divergent results in an attempt to use the cellular localization of BIRC5/survivin for prediction of BC recurrence [ 25 , 58 , 59 ]. We demonstrated that BIRC5/survivin analysis on the mRNA or protein levels was sufficiently sensitive to predict clinical outcome, disregarding its cellular localization.…”

“…Recent meta-analysis revealed high BIRC5/survivin expression in BC to be predictive for disease-free and overall survival in hormone receptor negative BC [ 24 ]. However, a prospective Danish study was unable to establish a link between BIRC5/survivin expression ratio between the cytoplasm and nucleus, and the recurrence rate in a cohort of ER-positive BC patients [ 25 ]. Nevertheless, overexpression of cytoplasmic BIRC5/survivin was found to be associated with an increased risk of recurrence in ER-negative BC patients [ 24 ].…”

Prognostic value of XIAP and survivin expression in locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy

“…In cancer cells, cytosol survivin has been related to inhibition of apoptosis, while nuclear survivin is more likely to be involved in aberrant proliferation. Collin et al , in a recently published case-control study encompassing a large patient group ( n = 541), did not confirm the association between cytoplasmic or nuclear survivin expression and breast cancer recurrence [ 51 ]. However, some previously conducted meta-analyses have revealed that cytoplasmic survivin overexpression is an unfavourable prognostic factor, while high expression of nuclear survivin has no impact on breast cancer prognosis [ 25 , 26 ].…”