Abstract P4-01-23: Clinical significance of serum PSA in breast cancer patients
Authors: T Hanamura, K Ohno, S Houkibara, H Murasawa, T Nakamura, H Watanabe, M Kaizuka, S Sawano, H Koyama, K-i Ito
Journal: Cancer Research (2019)

Abstract Background: Recent preclinical data suggest that estrogen receptor (ER) positive breast cancer (BC), may switch from dependence on ER to androgen receptor (AR) as possible mechanism of resistance to ER-targeted endocrine therapy. AR dependency has also been suggested in a subset of ER-, AR+ BC. Based on these findings, clinical trials testing AR-targeting therapies in BC have been conducted. However, predictive markers for response to this type of therapies remain to be elucidated. PSA is the product of an androgen-responsive gene produced also in BC, and serum PSA (sPSA) could be detected in BC patients by a highly sensitive assay. Hypothesis:If sPSA reflects AR dependency of BC, it might be useful as a predictive marker for response to AR-targeting therapy. Methods:In this study, we investigated whether tumor-derived sPSA could be detected in BC patient, and if it might reflect tumor biology. In metastatic breast cancer (MBC) patients continuously observed, sPSA was evaluated monthly by CLEIA method (detection sensitivity ≥ 3 ng/L). Similarly, sPSA was evaluated at arbitrary points in non-BC control and point analysis BC group enrolled regardless of clinicopathological factor or treatment history. In the observational group, the relationship between change in disease condition and sPSA was analyzed. Next, correlations between sPSA and various clinicopathological factors were analyzed using combined data of point analysis group and initial sPSA value of observation group. In this study, 146 BC (26 observation group and 120 point analysis group) and 99 control were enrolled. Results: In the observational analysis, 5 cases showed sPSA change well reflected the disease condition, but not in other 5 cases. In remaining 16 cases, sPSA was undetectable or the observation period was insufficient (&amp;lt;4m). In the point analysis, sPSA was detected in 28.3% and 28.1% in control and BC respectively. Although in pre-menopausal state, there was no significant difference in sPSA between control and BC (4.4 ± 6.98 ng/L vs 3.7 ± 5.5 ng/L), in post-menopausal state, sPSA was significantly higher in BC compared with control (0.7 ± 2.5 ng/L vs 64.6 ± 357.4 ng/L; P&amp;lt;0.05). In analysis limited to post-menopausal BC, sPSA was higher in MBC (de-novo stage 4 and recurrence) compared with non-MBC (Stage0-3) (106.0 ± 457.2 ng/L vs 2.1 ± 8.5 ng/L; P&amp;lt;0.05). Similarly, sPSA was higher in low ki-67 (&amp;lt;20%) cases compared with high ki-67 (≥20%) (105.7 ± 510.8 ng/L vs 30.5 ± 173.7 ng/L; p&amp;lt;0.05). There was no significant difference in sPSA due to histological type, ER or HER2 status and nuclear grade. In correlation analysis of quantitative data limited to post-menopausal MBC, sPSA was negatively correlated with Ki-67 (rS=-0.35, p&amp;lt;0.05) and positively correlated with treatment line of previous endocrine therapy (rS=0.27, p&amp;lt;0.05). It did not correlate with age, disease free interval, number of metastatic organs or treatment line of previous chemotherapy. Conclusion:Our data suggest that sPSA may be tumor-derived at least in post-menopausal MBC and may reflect some kind of tumor biological properties. These all findings justify further studies of the efficacy of sPSA as a predictive marker in AR-targeted therapy. Citation Format: Hanamura T, Ohno K, Houkibara S, Murasawa H, Nakamura T, Watanabe H, Kaizuka M, Sawano S, Koyama H, Ito K-i. Clinical significance of serum PSA in breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-23.