Positive results from NanoString's second clinical study of PAM50-based breast cancer assay

NanoString Technologies, Inc., a privately held provider of life science tools for translational research and developer of molecular diagnostic products, today announced positive results from the second clinical validation study of its in vitro diagnostic breast cancer assay based on the PAM50 gene expression signature. The study, which evaluated samples from more than 1,400 patients enrolled in the Austrian Breast & Colorectal Cancer Study Group 8 (ABCSG8) trial, met its primary and secondary objectives and demonstrated the ability of the PAM50 test to indicate the risk of distant recurrence in postmenopausal women with hormone receptor-positive (HR+) early-stage breast cancer treated with endocrine therapy alone. Results were presented by the study's investigators during the 2012 CTRC-AACR San Antonio Breast Cancer Symposium.

NanoString's PAM50-based breast cancer assay can provide a subtype classification based on the fundamental biology of an individual's breast tumor (referred to as intrinsic subtyping), as well as a prognostic score (referred to as the risk of recurrence, or ROR, score). The ROR score indicates the probability of cancer recurrence over 10 years in post-menopausal women with HR+ early-stage breast cancer who have been treated with endocrine therapy alone. Together with studies from the literature, the ROR score and intrinsic subtype have been shown to convey clinically relevant information about a patient's prognosis.

The aim of this study was to assess the performance of the ROR score in indicating distant recurrence for postmenopausal patients with HR+ early-stage breast cancer treated with endocrine therapy alone when the PAM50-based test is performed in a hospital pathology lab. Investigators at the British Columbia Cancer Agency (BCCA) performed NanoString's PAM50-based breast cancer assay on tumor samples from 1,478 participants in the ABCSG8 study that had been stored in formalin-fixed paraffin-embedded (FFPE) format using the nCounter^® Analysis System installed in BCCA's Center for Translational and Applied Genomics.

"The nCounter Analysis System is highly automated and fits into the workflow of a hospital pathology laboratory where it can accurately measure RNA extracted from standard FFPE tissue samples with minimal hands-on time," said Torsten Nielson, MD, PhD, Professor of Pathology at the University of British Columbia and lead pathology investigator of this study. "On these clinical specimens, 97% of the breast cancer samples that passed the pre-specified tissue and RNA metrics yielded intrinsic subtype and ROR results."

The ROR score and intrinsic subtype of the tumor were related to the outcome for each patient (median follow-up of 11 years) in the study and analyzed according to a prospectively defined analysis plan. The PAM50 ROR score added prognostic information about distant recurrence beyond the standard pathological variables in the study population (p<0.0001). In addition, the risk categories defined by pre-specified ROR score cut-points (low risk, intermediate risk, and high risk) separated the patients into risk groups with statistically significant different outcomes at 10 years. Finally, the results demonstrated that Luminal A subtypes have better outcomes than Luminal B subtypes independent of nodal status in postmenopausal women with HR+ early-stage breast cancer treated with endocrine therapy alone.

"This study demonstrates the ability of PAM50 to indicate risk of recurrence in postmenopausal women with either node-negative or node-positive HR+ early-stage breast cancer who are treated with endocrine therapy alone," said Michael Gnant, MD, Professor at the Medical University of Vienna, President of ABCSG and lead clinical investigator of the ABCSG8 study. "These results confirm the key findings of the TransATAC study presented last year, and together these two studies provide strong evidence for the PAM50 test's clinical validity."

The results of the TransATAC study, which included more than 1,000 samples from postmenopausal women with HR+ early-stage breast cancer, were presented by the study's investigators at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. NanoString has an exclusive worldwide license for the PAM50 gene signature to develop in vitro diagnostic and research products for breast cancer on its nCounter^® Analysis System. The clinical development program for NanoString's PAM50-based assay is designed to support both regulatory requirements for market-specific clearance or approval and its incorporation into breast cancer treatment guidelines worldwide. In September 2012, NanoString obtained the CE Mark for its PAM50-based assay, clearing the company to sell it in the European Union and other countries recognizing the CE Mark. The PAM50 gene signature has not been cleared for marketing in the United States, and the nCounter Analysis System is currently labeled for "Research Use Only".