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Gene-expression-based Biomarker Predicts Long-term Risk of Breast Cancer Recurrence

A comparison of three methods of predicting the risk of recurrence in women treated for estrogen-receptor (ER)-positive breast cancer finds that only the breast cancer index (BCI) – a biomarker based on the expression levels of seven tumor-specific genes – accurately identifies patients who continue to be at risk after five years of treatment with either tamoxifen or the aromatase inhibitor anastrozole. The study comparing the BCI with two other prognostic tests has been published online in Lancet Oncology.

bioTheranostics’ Breast Cancer IndexSM Molecular Test Identifies Risk for Early and Late Breast Cancer Recurrence, Lancet Oncology Study Finds

A study published online in The Lancet Oncology found that in a comparison of three methods of predicting the risk of recurrence of estrogen-receptor (ER)-positive breast cancer, only the Breast Cancer IndexSM (BCI) from bioTheranostics predicts risk for both early (0-5 years) and late (5-10 years) recurrence. The study provides important new information to guide patient treatment decisions at diagnosis and after several years of therapy.

NanoString Technologies Receives FDA 510(k) Clearance for Prosigna Breast Cancer Prognostic Gene Signature Assay

NanoString Technologies, Inc., (NASDAQ: NSTG) a provider of life science tools for translational research and molecular diagnostic products, recently announced that it has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) for its Prosigna™ Breast Cancer Prognostic Gene Signature Assay. Based on the PAM50 gene signature, Prosigna is the company’s first FDA-cleared in vitro diagnostic assay and uses the gene expression profile of cells found in breast cancer tissue to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay is performed using the nCounter® Dx Analysis System, which can be placed in qualified laboratories throughout the United States, empowering oncologists and pathologists to quickly and easily meet the testing needs of their breast cancer patients.

“Receipt of FDA 510(k) clearance for Prosigna marks a key milestone for NanoString and is an important step forward in the treatment of breast cancer. This achievement is a testament to the ongoing dedication and professionalism of our team, and the commitment of our collaborators,” said Brad Gray, President and Chief Executive Officer of NanoString Technologies. “Prosigna illustrates our approach of using nCounter technology to translate genomic discoveries into powerful in vitro diagnostic products, and it represents a significant growth opportunity beyond our robust life sciences research business.”

The Prosigna Assay is intended for use as a prognostic indicator for distant recurrence-free survival at 10 years, and is indicated for postmenopausal women with Stage I/II lymph node-negative or Stage II lymph node-positive (one to three positive nodes) hormone receptor-positive breast cancer who have undergone surgery in conjunction with locoregional treatment consistent with standard of care. For each patient, the Prosigna Assay reports the Prosigna Score (referred to as Risk of Recurrence Score, or ROR Score, in the scientific literature, including the TransATAC study recently published in the Journal of Clinical Oncology ) and a risk category based on both the Prosigna Score and nodal status. Node-negative patients are classified as low, intermediate or high risk, while node-positive patients are classified as low or high risk.

Other key features of the Prosigna Breast Cancer Prognostic Gene Signature Assay include:

  • All-in-one assay consumables, including RNA extraction kits, allowing laboratories to test as little as a single section of formalin-fixed paraffin embedded (FFPE) tumor tissue
  • High-throughput workflow allowing each nCounter Dx Analysis System to process up to 30 patient samples per eight hour work day
  • Automated generation of personalized full-color patient reports that can be quickly and easily shared electronically with ordering oncologists

Bruce Seeley, Senior Vice President & General Manager of Diagnostics of NanoString Technologies commented: “We believe that the compelling clinical data, clear patient reporting, and unique delivery model position Prosigna for success in the U.S. market. By integrating the Prosigna Assay into existing laboratory workflows, we are offering physicians and patients seamless and timely access to clinical insights and a powerful tool that can aid in making more informed treatment decisions.”

Prosigna-enabled nCounter Dx Analysis Systems are expected to be available for placement in high-complexity Clinical Laboratory Improvement Amendments (CLIA) certified laboratories late in the fourth quarter of 2013. Prosigna testing services are expected to be available through qualified U.S. clinical laboratories beginning in the first quarter of 2014.

Source: NanoString Technologies

Researchers Identify Splice Variant of Breast Cancer Gene that Can Mask Risk of Recurrence

Agendia, a leader in molecular cancer diagnostics, recently announced that researchers have identified a subset of breast cancer patients whose standard biomarker tests may incorrectly classify patients as low risk and benefitting from endocrine therapy. A study published last month in Breast Cancer Research and Treatment concluded that this subset of breast cancer patients may actually be at “high risk” of disease progression and benefit more from chemotherapy than endocrine therapy.

The researchers found that 2 percent of breast cancer patients tested, who were identified as estrogen receptor positive (ER+) and therefore potential candidates to benefit from endocrine therapy, actually had a variant of the estrogen receptor called “delta Exon 7 deletion”. This variant is missed by standard receptor testing and reported as receptor positive, when in fact the variant protein inhibits the normal estrogen signal in the cell that may prevent the patient from benefitting from routine endocrine therapy. Moreover these patients have a genomic profile of their tumor that suggests that 95% of these are “at high recurrence risk and would likely benefit from adjuvant chemotherapy,” the researchers concluded.

The researchers identified the importance of the delta Exon 7 deletion through a test called BluePrint®, which was developed by Agendia. BluePrint is one part of a suite of related breast cancer tests called Symphony, which provides a complete view of a patient’s prognosis and help guide their individual treatment decisions through genomic profiling.

“The researchers identified the presence of the Exon 7 variant of the estrogen receptor while trying to determine why some breast cancer patients who tested ER+ in the classical test for receptor status turned out to be of the ‘basal-like’ subtype by the BluePrint assay, which indicates a lack of a functional estrogen pathway, noted Stephanie R. Akbari, M.D., Medical Director of the Reinsch Pierce Family Center for Breast Health at Virginia Hospital Center, a member of the research team. Medical experts have long established that ER+ tumors typically benefit from hormonal therapies, but we also know that not all patients with ER+ tumors benefit from this therapy. “This finding may help identify those patients that are unlikely to benefit from hormonal therapy.”

Dr. Akbari said. “Our findings show that, as we discover the importance of splicing variants such as Exon7, additional molecular subtyping of a patient’s tumor is necessary to reach a more accurate understanding of the disease.”

Agendia CEO David Macdonald said, “Agendia’s Symphony is the only commercially available test suite that provides molecular subtyping and can identify the growing body of important genetic variants such as Exon 7. This research underscores Agendia’s commitment to ongoing discovery and collaboration between industry and physician-directed research in bringing scientific advances into clinical practice.”

Study: Estrogen receptor splice variants as a potential source of false-positive estrogen receptor status in breast cancer diagnostics [Breast Cancer Research and Treatment]

Source: Agendia

Studies Show bioTheranostics’ Breast Cancer Index Identifies Breast Cancer Patients at Risk for Early and Late Recurrence, and Predicts Benefit from Extended Endocrine Therapy

bioTheranostics, developer of innovative molecular diagnostics, reported results from two new studies evaluating the performance of its Breast Cancer Index (BCI) biomarker assay in estrogen-receptor positive (ER+), early stage breast cancer. Study results showed that BCI predicts which women with early stage ER+ breast cancer are at risk for early and late distant recurrence, and which are most likely to benefit from continuing treatment with endocrine therapy after completing five years of tamoxifen.

BCI is a combinatorial biomarker with a novel mechanism of action composed of Molecular Grade Index (MGI) and the two-gene expression ratio HOXB13/IL17BR (H/I).

In a study published online in the Journal of the National Cancer Institute, tumor samples from 83 patients with breast cancer recurrence were matched to 166 patients without disease recurrence from the MA.17 trial, a landmark randomized clinical study that demonstrated improved disease-free survival with extended letrozole therapy in postmenopausal patients with ER+ breast cancer who were recurrence-free following an initial five years of tamoxifen therapy. In patients receiving extended endocrine therapy, a high H/I gene expression ratio, as measured by the BCI assay, remained significantly associated with benefit from extended endocrine therapy (p=0.0061), representing a 16.5 percent reduction in the risk of recurrence with extended letrozole treatment compared with placebo. Patients with low H/I did not benefit from extended letrozole treatment. The study authors concluded that the BCI assay identifies a subgroup of breast cancer patients disease-free after five years of tamoxifen therapy who are at risk for late recurrence, and that high H/I predicts benefit from extended endocrine therapy. The study was conducted by researchers from leading institutions, including Massachusetts General Hospital.

A second study, published online in the journal Clinical Cancer Research, examined the ability of the BCI test to predict early (0-5 years) and late (>5 years) distant recurrence in ER+, lymph node-negative breast cancer patients. The study was a retrospective analysis of tumor samples from tamoxifen-treated patients from the randomized, prospective Stockholm trial (n=317) and a multi-institutional cohort from two academic medical centers (n=358). Within the Stockholm trial cohort, BCI stratified the majority (~65 percent) of patients as low risk, with <3 percent distant recurrence rate for 0-5 years and 5-10 years. In the multi-institutional cohort, which had larger tumors, 55 percent of patients were classified by BCI as low risk, with a <5 percent distant recurrence rate for 0-5 and 5-10 years. For both groups, the BCI assay was the most significant prognostic factor beyond standard clinicopathological factors for 0-5 and >5 years. The authors concluded that the ability of the BCI test to assess risk of both early and late distant recurrence has clinical utility for decisions of chemotherapy at diagnosis and for decisions about extended endocrine therapy beyond five years.

Richard Ding, president and CEO of bioTheranostics, said there is a growing need for novel biomarkers in ER+ early stage breast cancer that guide disease management beyond the initial 5-year window. “Breast Cancer Index is the only biomarker test that has been shown in prospective trials to predict the benefit of extended endocrine therapy,” Ding said. “The results of these key studies illustrate the importance of the BCI test in identifying which patients are at risk for early and late breast cancer recurrence, and who among them will benefit from extended endocrine therapy, which is of significant clinical value. This critical information should allow many women to avoid unnecessary treatment and for the clinical focus to be on those in most need of therapy.”

Study: Prediction of Late Disease Recurrence and Extended Adjuvant Letrozole Benefit by the HOXB13/IL17BR Biomarker

Study: Breast Cancer Index Identifies Early-Stage Estrogen Receptor–Positive Breast Cancer Patients at Risk for Early- and Late-Distant Recurrence

Source: Business Wire