Wwox expression may predict benefit from adjuvant tamoxifen in randomized breast cancer patients

Abstract

Reduced or absent Wwox expression has recently been associated with tamoxifen resistance in breast cancer and has also been proposed as a candidate predictive marker for treatment. We aimed to investigate the correlation of Wwox expression with the outcome of tamoxifen treatment by examining tissues from 912 randomized breast cancer patients. Paraffin-embedded tissues from patient tumors were arranged on tissue microarray, and Wwox protein was stained using immunohistochemistry. After microscopic examination, the results were analyzed with Cox regression, Kaplan-Meier survival curves and the log-rank test. In the group of cases having a tumor absent for Wwox expression, there was no difference in recurrence-free survival between treated and untreated patients (P=0.81). For treated cases with a tumor expressing moderate or strong Wwox protein, recurrence-free survival was improved (P=0.001 and P=0.003, respectively). The test for interaction between Wwox and treatment response demonstrated a decreased risk of recurrence for treated patients with a moderate or strong Wwox expression (HR=0.31, 95% CI 0.10-0.98 and HR=0.28, 95% CI 0.08-0.97, respectively). Our results indicate that patients with high expression of Wwox may gain more benefit from treatment with tamoxifen.

Reduced expression of the WW domain-containing oxidoreductase in human hematopoietic malignancies

“…Supporting evidence from another study similarly showed that WWOX protein expression was significantly elevated in the 5-Aza-CdR-treated ovarian cancer group (28). Recently published data indicated that in the treated breast cancer cases with a tumor expressing moderate or strong WWOX protein, recurrence-free survival was improved (29). Additionally, a previous study conducted by Guler et al (30) revealed that reduced or absent WWOX expression was associated with tamoxifen resistance in breast cancer, hinting of the potential of WWOX in predicting tamoxifen response.…”

“…WWOX is a tumor suppressor gene that maps to the common fragile site FRA16D and is involved in carcinogenesis and cancer progression in a number of carcinoma types (1,19,20). The bulk of the data documented have shown that the expression of WWOX/WWOX was lost or reduced in various types of solid cancers (2)(3)(4)(5)(6)(7)(8)(9)(10). Similarly, the aberration or absence of WWOX/WWOX expression in primary hematopoietic malignancies has also been reported (11)(12)(13)(14)(15)(16).…”

“…Since its discovery, WWOX/WWOX has been shown to exhibit reduced or no expression in a range of neoplastic diseases of varying locations, such as the lungs, breasts, bladder, ovaries, esophagus and pancreas (2)(3)(4)(5)(6)(7). Moreover, abnormal WWOX/WWOX expression profiles had been reported to be associated with a poor prognosis in carcinomas (8)(9)(10). Therefore, WWOX is expected to be a potential target for the gene-targeted therapy of human carcinomas.…”

The Evaluation of WBP2NL-Related Genes Expression in Breast Cancer

“…It has been reported that WWOX acts as a tumor suppressor, and plays a role in apoptosis, and it has been lost in cervical cancer [38]. It has been indicated that breast cancer patients with high expression of WWOX have good prognosis to treatment [39]. The SGSM family members mediate the small G protein RAB-mediated signal transduction and vesicular transport pathway [40].…”

Roles of the WWOX in pathogenesis and endocrine therapy of breast cancer

“…The results indicated that high expression of WWOX was associated with better outcome of tamoxifen treatment. 45 In breast cancer cell lines, loss of WWOX expression induces the release of Ap2g from the cytoplasma to the nucleus and the up-regulation of human epidermal growth factor receptor 2 (Her2). Increased Her2 promotes the growth of cancer cells against endocrine therapy for breast cancer and leads to tamoxifen resistance.…”