Lugano-CH, Brussels-BE, 2 May 2013
A test that measures the expression levels of 58 genes in oestrogen receptor-positive breast cancers can effectively differentiate between patients who are at higher and lower risk for having their cancer recur elsewhere in the body more than five years after diagnosis, researchers report.
The new findings show that better individual risk prediction for women with these cancers is getting nearer, says study author Prof Michael Gnant from the Medical University of Vienna, Austria.
Prof Gnant reported the findings at the 5th IMPAKT Breast Cancer Conference in Brussels, Belgium. The IMPAKT meeting presents cutting edge, ‘translational’ breast cancer research that is beginning to have an impact for patients.
Metastasis after 5 years of follow-up is an important research issue, particularly in hormone-receptor positive breast cancer, Prof Gnant explains.
“Despite all great progress we have made in the treatment of this most frequent subtype of breast cancer, some patients develop metastasis many years after their initial diagnosis. Extending adjuvant endocrine therapy to prevent this is an option, but comes with substantial side-effects and cost for society, and should therefore be reserved for those patients who really need it. Thus, better defining individual risk for late metastasis is an important medical and scientific need,” Prof Gnant says.
The PAM50 Risk of Recurrence (ROR) score used by the researchers in this study directly measures the expression levels of 58 different genes (50 discriminator genes and 8 controls).
Prof Gnant and colleagues performed the PAM50 analysis on 1,478 patients who had taken part in the ABCSG-8 trial, which ran from 1996 to 2009. They found that the PAM50 ROR score provided significant prognostic information in addition to clinical factors with respect to late distant-relapse-free survival.
After 11 years of median follow-up, of patients who were classified by the test as having low risk, 98.7% had not had a late metastasis between 5 and 10 years of follow-up, compared to 91.5% of those with a high PAM50 ROR score. This was true both for node-positive and node-negative disease.
“It makes a huge difference whether a patient looks at an individual risk of 1.3% or 8.5% between years 5 and 10. This is more than six times as much risk. Such important information may well be implemented into individual treatment decisions,” Prof Gnant says.
The researchers conclude that the PAM50 ROR score can successfully be used to differentiate patients with respect to their risk for late metastasis, in addition to established clinical and pathological risk factors.
This ability to predict late metastasis may be used in the future to identify patients with endocrine-responsive breast cancer who need or alternatively who can be spared extended adjuvant therapy, they say.
“We have to admit that at this point we cannot prove definitely that we will improve the outcome in patients we have now identified as high risk by extending their adjuvant therapy, but it appears logical that this may be the case. At least as important, if we can define an individual patient reliably as low risk, we can spare her the burden of unnecessary treatment extension,” Prof Gnant says.
Commenting on the results, Dr W Fraser Symmans, Professor and Director of Research Operations, Department of Pathology at the University of Texas M.D. Anderson Cancer Center, USA, said they were important for prognostic testing of early breast cancers and for confidently limiting the duration of endocrine therapy to 5 years for women with low-risk disease.
“In the last 6 months it has become clear that three prognostic tests, including the PAM50 ROR score, have similar prognostic utility that holds for up to 15 years after initial diagnosis. It is particularly exciting for the diagnostic community that such newer tests could be offered by pathology laboratories, and might not require centralised testing. I look forward to seeing the results of studies that report the inter-laboratory consistency of these tests for determining the long-term prognosis for early breast cancer patients who received 5 years of adjuvant endocrine therapy,” Dr Symmans said.
Notes to Editors
Session info: Best Abstract Session
Friday, 3 May 2013, 10:45 AM – 12:15 PM (CEST). Place: Gold Hall
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About the Breast International Group (BIG)
The Breast International Group (BIG) is a non-profit organisation for academic breast cancer research groups from around the world, based in Brussels, Belgium.
Founded by leading European opinion leaders in 1996, BIG now constitutes a network of 50 groups based in Europe, Canada, Latin America, Asia and Australasia. These research entities are tied to several thousand specialised hospitals and research centres worldwide. More than 30 clinical trials are run or are under development under the BIG umbrella. BIG also works closely with the US National Cancer Institute (NCI) and the North American Breast Cancer Groups (NABCG), so that together they act as a strong integrating force in the breast cancer research arena.
To make significant scientific advances in breast cancer research, reduce unnecessary duplication of effort, and optimally serve those affected by the disease, large-scale cooperation is crucial. Therefore BIG facilitates breast cancer research at international level, by stimulating cooperation between its members and other academic networks, and collaborating with, but working independently from, the pharmaceutical industry. To find out more about BIG, please visit: www.breastinternationalgroup.org
About the European Society for Medical Oncology (ESMO)
The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology and promoting a multidisciplinary approach to cancer treatment and care.
ESMO’s mission is to advance cancer care and cure through fostering and disseminating good science that leads to better medicine and determines best practice.
As a trusted organization with 35 years of experience, ESMO serves its members and the oncology community through: a brand of excellence in post-graduate oncology education and training; leadership in transforming evidence-based research into standards of cancer care in Europe; dedicated efforts to foster a more favorable environment for scientific research; innovative international platforms to share expertise, best practices and disseminate the most up-to-date scientific research to as wide an audience as possible.
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Abstract 53 O_PR
PREDICTING RISK FOR LATE METASTASIS: THE PAM50 RISK OF RECURRENCE (ROR) SCORE AFTER 5 YEARS OF ENDOCRINE THERAPY IN POSTMENOPAUSAL WOMEN WITH HR+ EARLY BREAST CANCER: A STUDY ON 1,478 PATIENTS FROM THE ABCSG-8 TRIAL
M. Gnant1, M. Filipits2, P. Dubsky3, M. Rudas2, M. Balic4, R. Greil5, S. Ferree6, C. Schaper7, J.W. Cowens6, T. Nielsen8
1Department Of Surgery And Comprehensive Cancer Centre, Medical University of Vienna, Wien/AUSTRIA, 2Research, ABCSG, Vienna/AUSTRIA, 3Department Of Surgery, Medical University of Vienna, Vienna/AUSTRIA, 4Internal Medicine, University of Graz, Graz/AUSTRIA, 5Salzburg, PMU, Salzburg/AUSTRIA, 6Suite 2000, NanoString Technologies 530 Fairview Avenue N, Seattle/UNITED STATES OF AMERICA, 7Raqa, My, Redwood Shores/UNITED STATES OF AMERICA, 8Cancer Agency, British Columbia, Vancouver/CANADA
Introduction: Despite great improvements in overall outcomes of endocrine-responsive breast cancer, the main challenge in improving long-term cure of these patients remains their inherent risk for late relapse. Particularly in patients with initially favorable molecular characteristics (e.g. luminal A), the annual relapse risk persists well beyond 5 years follow-up. Extending adjuvant therapy may be an option to reduce risk of late metastasis. It would be of great value to differentiate patients at high vs. low risk of late relapse for clinical decision making and patient counseling. The goal of this work is to evaluate the ability of the PAM50 signature to predict late metastasis in a large cohort of endocrine responsive breast cancer.
Methods/Patients: NanoString has developed a PAM50-based breast cancer gene signature assay that is used to categorize a breast tumor specimen into intrinsic breast cancer subtypes and to provide a risk-of-recurrence (ROR) score. Using the nCounter DX Analysis System, this assay directly measures the mRNA expression levels of 58 different genes in a single hybridization. NanoString’s assay has been optimized to be performed with FFPE tissue samples in local hospital pathology laboratories. This ROR score has been clinically validated in several studies, and has been suggested to predict late recurrences in a transATAC study. Out of 3,714 patients of ABCSG-8, 1,671 patients could be re-consented to this study, with 1,620 FFPE blocks available. Out of those, 1,478 (91.2%) passed the PAM50 analysis.
Results: PAM50 ROR provided significant additional prognostic information to clinical factors with respect to late distant-relapse-free survival (DRFS) (Chi-Square 15.3, p<0.0001) and late RFS (Chi-Square 11.4, p=0.0007) in multivariate models, with probabilities for DRFS after year 5 of 98.7% for low ROR patients vs. 91.5% for high ROR patients. This was true both for node-positive and node negative disease.
Discussion: PAM50 ROR can successfully be used to differentiate patients with respect to their risk for late metastasis, in addition to established clinicopathological risk factors. This ability to predict late metastasis may be used in the future to identify patients with endocrine-responsive breast cancer who need or alternatively who can be spared extended adjuvant therapy.
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