Abstract
Background: We analyzed mRNA profiles of prostate cancer related genes in circulating tumor cells (CTCs) of primary, non-metastatic triple-negative breast cancer (TNBC) patients (pts) before and after neoadjuvant chemotherapy to elucidate the potential of prostate cancer targets in this BC subgroup.Method: Blood from 41 TNBC pts (n = 41 before / 26 after therapy) was analyzed for CTCs applying the AdnaTest EMT-2/Stem Cell Select. Multimarker RT-qPCR allowed the detection of the prostate specific antigen PSA, the prostate specific membrane antigen PSMA, full-length androgen receptor (AR-FL), and AR splice-variant seven (AR-V7).Results: Before therapy, at least one prostate cancer related gene was detected in 15/41 pts (37%). Notably, in 73% of AR-FL positive cases, AR-V7 was co-expressed. After therapy, CTCs of only one patient harbored prostate cancer related genes. AR-V7+ and PSMA+ CTCs significantly correlated with early relapse (p = 0.041; p = 0.00039) whereas PSMA+ CTCs also associated with a reduced OS (p = 0.0059). This correlation was confirmed for PSMA+ CTCs in univariate (PFS p = 0.002; OS p = 0.015), but not multivariate analysis.Conclusion: Although CTCs that expressed prostate cancer related genes were eliminated by the given therapy, PSMA+ CTCs significantly identified pts at high risk for relapse. Furthermore, AR inhibition, often discussed for this BC subgroup, might not be successful in the primary setting of the disease since we identified AR-FL+ CTCs together with AR-V7+ CTCs, associated with therapeutic failure.
Highlights
Triple-negative breast cancer (TNBC), accounting for 15–20% of all breast cancers (BC), has an destructive behavior which is associated with poor prognosis [1, 2]
Immunotherapy is under investigation in this patient subset and has already shown a significantly improved pathological complete response (pCR) adding the checkpoint inhibitor anti-PD-1, pembrolizumab, to Neoadjuvant chemotherapy (NACT) in early TNBC with a trend seen for a prolonged event free survival [9]
At least one prostate cancer related gene was detected in 15/41 pts (37%)
Summary
Triple-negative breast cancer (TNBC), accounting for 15–20% of all breast cancers (BC), has an destructive behavior which is associated with poor prognosis [1, 2]. Among the different subtypes defined [12], the luminal androgen receptor (LAR) subtype was found to be enriched in mRNA expression of androgen receptor (AR) and several downstream AR targets, resulting in enhanced sensitivity to the AR antagonist bicalutamide [13] which qualifies AR as a suitable target in LAR TNBC In this context, ongoing clinical trials are testing the effectiveness of other AR inhibitors in TNBC, including abiraterone and enzalutamide, commonly prescribed in PCA [14,15,16,17]. We analyzed mRNA profiles of prostate cancer related genes in circulating tumor cells (CTCs) of primary, non-metastatic triple-negative breast cancer (TNBC) patients (pts) before and after neoadjuvant chemotherapy to elucidate the potential of prostate cancer targets in this BC subgroup
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