[180] BTG2 Loss Is Associated with Poor Prognosis in HER2+ Breast Cancer

Marco M Hefti, Nicholas Knoblauch, Andrew H Beck. Beth Israel Deaconess Medical Center, Boston, MA

Background: B-cell translocation gene 2 (BTG2) is a key regulator of cell proliferation and a tumor suppressor in breast cancer1,2. BTG2 inhibition enhances growth and migration of breast cancer cells via stabilization of the HER ligands NRG1b and epiregulin.3 We thus examined the effect of BTG2 on survival in breast cancer, particularly in HER2-type cancers.
Design: We used a previously described collection of publicly available gene expression profiling data sets4. Gene expression was scaled across the entire data set for the overall survival analysis and within each subtype for the molecular subtype analysis.
Results: A total of 1173 patients had available survival data. BTG2 was significantly predictive of overall survival (p<10-3) on univariate Cox regression but not in a model that included HER2, ER, age, grade, nodal status, and size (p=.144). We then examined each molecular subtype individually. BTG2 was associated with survival in HER2+ molecular subtype (p=.002) but not for Luminal A, Luminal B, or Basal (p=.901, .325, and .579 respectively; Table 2). The interaction term BTG2*HER2 was significantly associated with survival (p=.031) when included in a multivariate model as above, but BTG2*ER was not (p=.480).
Conclusions: Our data show that BTG2 is associated with prognosis only in HER2+ breast cancer. These data suggest that BTG2 may play a key functional role in regulation of breast cancer growth and metastasis by HER2. BTG2 warrants further investigation as a possible therapeutic target and mechanism for HER2-antagonist resistance.

Cox Regression of BTG2 on Survival by Breast Cancer Subtype
Subtypenp-valueOR95% CI
HER21610.0020.6650.551 - 0.864
Luminal A2940.9011.0160.786 - 1.314
Luminal B4080.3250.9100.753 - 1.099
Basal2800.5791.0550.874 - 1.273

1. Kawakubo H, Brachtel E, Hayashida T, et al. Loss of B-cell translocation gene-2 in estrogen receptor-positive breast carcinoma is associated with tumor grade and overexpression of cyclin d1 protein. Cancer research 2006;66:7075-82.
2. Mollerstrom E, Kovacs A, Lovgren K, et al. Up-regulation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray. BMC cancer 2010;10:296.
3. Takahashi F, Chiba N, Tajima K, et al. Breast tumor progression induced by loss of BTG2 expression is inhibited by targeted therapy with the ErbB/HER inhibitor lapatinib. Oncogene 2011;30:3084-95.
4. Haibe-Kains B, Desmedt C, Loi S, et al. A three-gene model to robustly identify breast cancer molecular subtypes. Journal of the National Cancer Institute 2012;104:311-25.
Category: Breast

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 51, Tuesday Afternoon


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