Abstract P4-17-09: Clinicopathological and prognostic significance of preoperative PGC-1alpha plasma levels in male breast cancer patients

Abstract

Abstract Background: Unlike female breast cancer (fBC), male breast cancer (mBC) holds clinicopathological, radiological, and genetic differences including histologic grade that is often not correlated with clinical outcomes and most being ER/PR positive and Her2 negative. Recently, PGC-1α (hypoxia-related protein, expressed preferentially in cancer cells to enhance oxidative phosphorylation, mitochondrial biogenesis and functional motility/metastasogenesis) has been identified as a prognostic marker for fBC, but its value and impact in mBC have not been studied. Our objective was to assess the utility of PGC-1α as a prognostic marker and an indicator for disease-free survival (DFS) in mBC. Materials & Methods: 7000 female and 23 male patients de novo diagnosed with breast cancer, at the Breast Center, Yangpu Hospital, Tongji University School of Medicine, as well as 30 males with lesions that were non-tumorous (non-mBC, controls) were included prospectively between September 2012 and August 2018. Propensity Score Matching was used to balance confounding factors. Results: Mean PGC-1α plasma levels were significantly higher in fBC compared to mBC cohorts (248.9 ng/dl (95% CI 242.9-254.8) vs 224.9 ng/dl (95% CI 202.9-246.9, P =0.040), though after propensity matching, no differences were noted (225.7 ng/dl (95% CI 202.5-248.7) vs 204.5 ng/dl (95% CI 194.3-214.8, P=0.07). In a total, 681 (658 females and 23 males) out of 723 patients for a median of 43 months (range of 3 to 82 months). By the end of follow-up period, 16.6% (109/658) female patients and 21.7% (5/23, p-NS) male patients had local recurrence and/ or metastasis, 5.6% (38) died, 48.5% (33) due to breast cancer (4.7% (31) females and 8.7% (2) males. In unmatched samples, there were no differences in DFS between fBC and mBC (P = 0.439, log-rank test). After dichotomous division of unmatched patient samples into two groups by median of PGC-1α plasma levels 246.8 ng/dl, all patients with high PGC- 1α plasma levels (>246.813 ng/dl) had a higher risk of recurrence than those with low PGC-1α plasma levels (P= 0.008). When calculated only for unmatched female patients, the results were similar: patients with high PGC- 1α plasma levels (>246.813 ng/dl) had a higher risk of recurrence than those with low PGC-1α plasma levels (P= 0.016). However, in matched samples, 6.4% (5/78) of females and 22.7% (5/22) males had recurrences and the male DFS was significantly poorer than in women (P < 0.033) despite similar baseline clinicopathologic characteristics. After the dichotomous division of matched patient samples into two groups by median of PGC-1α plasma levels of 211.5 ng/dl, 47.4% (37/78) female and 59.1% (13/22) male patients showed high PGC-1α plasma levels (P = 0.334). Despite comparable clinicopathological features, patients with lower PGC- 1α plasma levels (<211.5 ng/dl) had a better DFS compared to those with high PGC-1α plasma levels (P = 0.05). Conclusion: PGC-1α appears to be an independent marker of poor prognosis and more aggressive cancer characteristics in mBC, with a stronger prognostic value than in fBC. It may represent a non-invasive, innovative option to identify high-risk mBC individuals, predict the outcome, monitor treatment and screen for disease recurrence. Therefore, the marker can assist to determine, tailor and alternate therapy course for the highly fatal disease of mBC, where guidelines are still missing and most therapeutic options are transferred from fBC. Furthermore, inhibition of PGC-1α pathways might be a promising antitumor management option. Citation Format: Ewelina Maria Biskup, Fengfeng Cai, Steven Lindheim. Clinicopathological and prognostic significance of preoperative PGC-1alpha plasma levels in male breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-17-09.