Diagnostic Assay Improves Outcomes Prediction in Early Breast Cancer, Nixing Need for Chemo

Diagnostic Assay Improves Outcomes Prediction in Early Breast Cancer, Nixing Need for Chemo
Diagnostic Assay Improves Outcomes Prediction in Early Breast Cancer, Nixing Need for Chemo

CHICAGO, IL—Outcome prediction for postmenopausal patients with node-positive hormone receptor-positive (HR+) early breast cancer can be improved using the Prosigna® PAM50 in vitro diagnostic assay, potentially negating the need for adjuvant chemotherapy, a study presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting has found.

“To our knowledge, this is the first genomic study of breast cancer on a comprehensive nationwide population,” stated Bent Ejlertsen, MD, PhD, of the Danish Breast Cancer Cooperative Group (DBCG).

The combined analysis of 2 randomized trials, TransATAC and ABCSG8, was designed to validate the PAM50 risk of recurrence (ROR) score to predict 10-year distant recurrence for subgroups of a comprehensive DBCG cohort with one, two, or three positive nodes. The goal was to identify those with one positive node (N1) who “may be spared overtreatment with chemotherapy,” Dr. Ejlertsen said.

Patients with HR+ early breast cancer and N1 are routinely treated with both endocrine therapy and chemotherapy. However, “identification of N1 patients with good outcome who may be spared chemotherapy remains an elusive goal,” he reported.

The study collected primary formalin-fixed, paraffin-embedded (FFPE) tumor blocks and follow-up data from 1,480 Danish women in the population-based DBCG database diagnosed from 2000 to 2003 with HR+, postmenopausal, N1 early breast cancer who were treated with endocrine therapy alone.

The Prosigna® Breast Cancer Prognostic Gene Signature Assay PAM50 is a decentralized test indicated for use with FFPE tissue. Using a proprietary algorithm that compares the gene expression profile of a patient's tumor with one of four PAM50 prototypical molecular profiles, an individualized score is generated on a scale of zero to 100 that correlates with the probability of distant recurrence with 10 years.

Based on prespecified cutoffs varied by number of patient nodes, the PAM50, run on the NanoString nCounter Analysis System, categorized patients as low (<10%), intermediate (10% to 20%), or high risk (>20%). Multivariate analyses were performed to assess the ability of PAM50 to predict distant recurrence in patients with one, two, or three positive nodes in each risk group.

A total of 1,466 women (99%) passed PAM50 quality control; 809 had 1 positive node; 426 had 2 positive nodes; and 231 had 3 positive nodes. Median follow-up was 9.25 years.

The investigators found that the PAM50 ROR score identified low-risk N1 patients with outcome equivalent to N0 disease, identifying at least 37% of patients with 1 positive node and 15% with 2 positive nodes who had an excellent prognosis.

The 10-year distant recurrence for women at low risk was 3.6% for one node and 4.6% for two positive nodes and not available for three positive nodes; for those at intermediate risk, it was 14.9% for one positive node, 8.7% for two positive nodes, and 0% for three positive nodes; and for high risk, 21.0% for one positive node, 20.7% for two positive nodes, and 26.1% for three positive nodes.

Dr. Ejlertsen noted that a sequential primary analysis showed both the continuous ROR score and the ROR risk categories added statistically significant prognostic information, improving outcome prediction for patients with one (P<0.0001), two (P<0.0001), or three positive nodes (P<0.008).

Sean Ferree, PhD, of NanoString, told Cancer Therapy Advisor that one of the next steps is to determine whether PAM50 ROR scores can predict which patients can stop adjuvant hormonal therapy after 5 years, versus the 10 years currently recommended by ASCO guidelines.


1. Ejlertsen B, Jensen M-B, Eriksen JO, et al. Validation of prediction of distant recurrence (DR) by Prosigna (PAM50) in subgroups of a Danish Breast Cancer Cooperative Group (DBCG) cohort of node-positive (N1), hormone receptor positive (HR+), postmenopausal early breast cancer (EBC) patients allocated 5yr of endocrine therapy (ET). J Clin Oncol. 2015:33;(suppl; abstr 513)

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