Circulating Tumor Cells Expressing the Prostate Specific Membrane Antigen (PSMA) Indicate Worse Outcome in Primary, Non-Metastatic Triple-Negative Breast Cancer

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.

Protein analysis of extracellular vesicles to monitor and predict therapeutic response in metastatic breast cancer

“…7b–i ). The correlation between PSMA overexpression and early relapse of BC was also observed in CTCs 48 . To validate the performance of the EV P signature in the prognostic prediction of PFS, we further collected 16 plasma samples from MBC patients prior to treatment.…”

Expression of Prostate Specific Membrane Antigen (PSMA) in Breast Cancer

“…Patients with PSMA-positive CTCs before undergoing chemotherapy were less likely to achieve pathological complete remission after chemotherapy. Recurrence occurred earlier if PSMA expression was detected (p = 0.0039) and overall survival rates were lower (p = 0.0059) 42 . Evaluation of the PSMA status of CTCs could help to predict the response to PSMA-targeted therapy in triple-negative breast cancer.…”

“…Die Patientinnen, die vor dem Erhalt einer Chemotherapie PSMA-positive CTCs hatten, erreichten nach jener Therapie weniger häufig pathologische Komplettremissionen. Bei einer Expression des PSMAs kam es früher zu einem Rezidiv (p = 00 039) und zu einem geringeren Gesamtüberleben (p = 0,0059) 42 . Gegebenenfalls könnte eine Evaluation des PSMA-Status auf CTCs das Ansprechen einer PSMA-gerichteten Therapie beim triple-negativen Mammakarzinom vorhersagen.…”

Cyclin-dependent Kinase 4/6 Inhibitor Palbociclib in Combination with Ralaniten Analogs for the Treatment of Androgen Receptor–positive Prostate and Breast Cancers

“…However, clinical samples of breast cancer can express both fulllength AR and AR-V7 (13)(14)(15)(16). Recently it was shown that expression of AR-V7 measured in circulating tumor cells of patients with metastatic breast cancer was associated with bone metastases and also failure of TNBC to therapies (13,52). Thus, application of AR-NTD inhibitors such as EPI-7170 that inhibit the transcriptional activities of both AR-V7 and full-length AR (23,25,26) may be beneficial for the treatment of TNBC as well as CRPC.…”