Sperm associated antigen 5 (SPAG5) predicts resistance to endocrine therapy and sensitivity to chemotherapy in oestrogen receptor positive (ER+) breast cancer (BC): A tool for BC precision medicine
Session type: Poster / e-Poster / Silent Theatre session
SPAG5 amplification and over-expression is common in luminal B breast cancer.
SPAG5 mRNA and protein expression and their association with over-all survival (OS) were determined in 4998 cases of ER+ BC. The association between the pathological complete response (pCR) to neoadjuvant anthracycline based chemotherapy (Neo-Adj-ACT) and SPAG5 expression (mRNA, protein) was evaluated in 1073 and 332 patients with ER+ BC respectively. The association between the dynamic response to the neoadjuvant endocrine therapy (Neo-Adj-ET) and SPAG5 mRNA expression was evaluated in 101 cases of ER+ BC. The association between distant relapse risk (DRR) and SPAG5 were tested in patients who received Neo-Adj-ACT or adjuvant chemotherapy in addition to 5-year adjuvant tamoxifen (mRNA: n=2819; protein: n=2501).
SPAG5-overexpression (SPAG5+; mRNA, protein) were associated with shorter OS (HR: 1.31, and 1.90, ps<0.001); respectively). Multi-variable analyses confirmed that SPAG5+ mRNA and protein expression were associated with higher pCR to Neo-Adj-ACT (OR: 1.90; p=0.041 and 23.03; p<0.0001; respectively). Down-regulation of SPAG5 has been observed after 2-weeks on Neo-Adj-ET and this predicted the dynamic clinical response .SPAG5 mRNA was highly expressed in non-responders vs., non-responders tumors (p=0.014). In patients received 5-year Tamoxifen with either lymph node positive (LN+) or LN negative (LN-), SPAG5+ BC (mRNA, protein) exhibited a two-fold increase in DRR (ps<0·0001). In contrast, in patients received Adj-ACT in addition to 5-year of Tamoxifen with either LN+ or LN-, SPAG5+ (mRNA, protein) exhibited a similar DRR to that with low SPAG5. ER+ patients with SPAG5+ mRNA, Adj-ACT in addition to 5-year of Tamoxifen has reduced 5-year-DRR by 28% for those with LN- (89% vs., 67%; p<0·001) and 22% for those with LN+ (76% vs., 54%; p<0·001), as compared to receiving 5-year Tamoxifen alone.
SPAG5 expression could be used as a prognostic and predictive tool for selecting and monitoring response to systemic therapies in ER+ BC.