Background: Breast cancers may recur following a long latency period, implying a dormant or quiescent phase, however little is known about the biology of cellular quiescence and few markers exist for this clinically important state. The purpose of this study was to investigate whether progesterone receptor membrane component family 1 (PGRMC1), which is expressed in both proliferating and quiescent tumor cells, is a prognostic biomarker in human breast cancer and to define its expression in breast cancer subtypes.

Methods: Seventeen publicly available data sets were combined to analyze PGRMC1 expression in 4,463 invasive breast cancers as a function of established molecular and phenotypic markers, estimates of cellular proliferation, and recurrence-free survival data. A gene expression signature-based assay was utilized to estimate cellular proliferation. Association between gene expression and relapse-free survival was assessed using Cox proportional hazards regression while controlling for the effect of proliferation.

Results: PGRMC1 expression was analyzed stratified by immunohistochemical and molecular subtype, tumor grade and size and compared with a known triple negative breast cancer biomarker, BCL11a. PGRMC1 and BCL11a each exhibited a robust positive correlation of comparable magnitude with proliferation across all breast cancer subtypes (r=0.27, p=6.5x10-17 and r=0.29, 1.7x10-41, respectively), and PGRMC1 was strongly associated with proliferation within the basal subtype (r=0.42, p=2.4x10-37 PGRMC1 versus 0.31, p=1.1x10-8 BCL11a). PGRMC1 expression was associated with a higher risk of early breast cancer recurrence (HR=1.25, 95% CI [1.12,1.39], p=6.4x10-5) and this association was dependent upon its association with proliferation.

Conclusions: PGRMC1 is a breast cancer proliferation biomarker. Further study of the function of this protein is warranted.

Citation Format: Elizabeth S. McDonald, Dhruv K. Pant, Tien-chi Pan, David A. Mankoff, Robert H. Mach, Lewis A. Chodosh. PGRMC1 is a biomarker for breast cancer cell proliferation and early relapse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5710. doi:10.1158/1538-7445.AM2017-5710