A new study, published online in the January 21, 2014 edition of Breast Cancer Research and Treatment, affirms that that the prognostic value of the 70-gene prognosis signature (MammaPrint?; Agendia) breast cancer test can accurately stratify a woman?s breast cancer risk for up to 25 years after she is first diagnosed with the disease.[1]
In the article, a team of American and Dutch researchers report on the longest-term follow-up study of its kind that confirms the durable accuracy of a unique genomic test for early-stage breast cancer. They concluded the 70-gene prognostic test has the statistically significant ability to predict, for up to a quarter-century, whether a newly diagnosed breast cancer patient is at low risk or high risk of a breast cancer recurrence. These findings expand on data about the test that were first published in the New England Journal of Medicine (NEJM) in 2002. [2] The original NEJM article showed how a more accurate method of prognostication – using gene-expression profile – is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria. This ultimately improves the selection of patients for adjuvant systemic therapy. [2]
… data show [the 70-gene prognosis signature test] retains its accuracy to classify the intrinsic long-term biology of a patient?s cancer…
Key measures
The study authors looked at two key measures – distant metastasis-free survival (DMFS)* and overall survival (OS) – in the set of 295 patients who were the subject of the earlier NEJM study. The accuracy of the 70-gene prognosis signature test results held true for both DMFS and OS, regardless of whether patients had node-negative or node-positive cancer. The data was generated from a group of consecutively treated women who were originally diagnosed between 1984 and 1995 and were less than 53 years of age at diagnosis. Median follow-up on these patients was 18.5 years ? far longer than has previously been reported for a test of this kind ? with a range of 15 to 25 years.
Address a significant concern
?These findings address a significant concern for physicians who treat patients according to the results of gene signatures like the 70-gene test, as to the long-term consequences of their treatment,? noted Stefan Gl?ck, M.D., Ph.D. ?This study provides the first conclusive evidence that a genomic test can accurately stratify patients? recurrence risk for many years after their breast cancer is first discovered.? Dr. Gl?ck is a medical oncologist with a specific focus on breast cancer and the Sylvester Professor in the Department of Medicine, Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center at the University of Miami, Leonard M. Miller School of Medicine Miami, FL.
Long-term study
?This remarkable long-term study demonstrates the ability of the 70-gene signature to accurately differentiate higher-risk from lower-risk women with regard to risk of recurrence and overall survival, at a time in their lives when breast cancer can have its most devastating impact on fertility, productivity, and capacity to fulfill childrearing responsibilities,? said Neil Barth, MD, an oncologist and Chief Medical Officer of Agendia. ?The data show MammaPrint retains its accuracy to classify the intrinsic long-term biology of a patient?s cancer. This accuracy persists regardless of changes that have occurred over time such as earlier patient diagnosis, expanded treatment options and improved efficacy of therapy. The study provides oncologists and their patients with an extra measure of confidence that the results of the test will remain accurate for many years forward.?
Clinical utility
A recent retrospectivestudy by Massimo Cristofanilli, M.D., FACP, (Photo) Director of the Jefferson Breast Care Centerand others shows that molecular subtypingprovides a more precise prognosis and gives physicians valuable guidance about the best treatment and more personalized management of early-stage breast cancer. This approach is based on an 
improved understanding of the molecular phenotypes of breast cancer. The study showed that molecular subtyping using the70-gene prognosis signature test leads to clinically significant prognostic and molecular stratification. [3]
The 70-gene prognostic ManaPrint provides definitive High Risk or Low Risk information about breast cancer recurrence, without ambiguous “intermediate” results. The test is performed as part of the Symphony? test panel, which also includes the BluePrint? assay, the most widely available test providing molecular subtyping of individual breast cancers. Furthermore, the BluePrint test, building on the foundational prognostic precision of 70-geneprognostic MammaPrint, classifies breast cancer into one of four molecular subtypes: Luminal A, Luminal B, HER2-type, and Basal-type. BluePrint also provides information about neoadjuvant chemosensitivity – the responsiveness to chemotherapy – more accurately than does an IHC/FISH assessment.
At the upcoming 31st Annual Miami Breast Cancer Conference, being held at the The Fontainebleau Miami Beach Hotel, Miami Beach, Florida, March 6 – 9, 2014, Steven C. Shivers, PhD., Charles E. Cox, MD., et al. reports emerging data about molecular subtyping of early-stage breast cancer and patients’ risk of disease recurrence. These new findings expand upon a scientific poster presented at the 2013 San Antonio Breast Cancer Symposium (SABCS). [4] The presented data focuses attention on genomic testing and molecular subtyping to refine breast cancer treatment.
Cox, a breast surgeon and CEO at the University of South Florida’s Breast Health Clinical and Research Integrated Strategic Program, will also chair a lunchtime symposium titled Molecular Subtypes: Clinical Implications for Breast Cancer Patients in Your Practice.
For more information:
[1] Long-term impact of the 70-gene signature on breast cancer outcome.Drukker CA, Van Tinteren H, Schmidt MK, Rutgers EJTh, Bernards R, Van de Vijver MJ, Van?t Veer LJ. Breast Cancer Research and TreatmentDOI 10.1007/s10549-013-2831-4 [Article][PubMed]
[2] Van de Vijver MJ, He YD, Van’t Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002 Dec 19;347(25):1999-2009.[Article][PubMed]
[3] Cristofanilli M, Turk M, Kaul K, Weaver J, Wesseling J, Stork-Sloots L, De Snoo F, Yao K. Molecular subtyping improves stratification of patients into diagnostically more meaningful risk groups. Cancer Research December 15, 2012; 72 (24), Supplement 3 doi: 10.1158/0008-5472.SABCS12-P3-05-01 [Abstract]
[4]Yao K, Goldschmidt R, Turk M, Kaul K, Wesseling J, Stork-Sloots L, De Snoo F, Cristofanilli M. MammaPrint and BluePrint in early breast cancer: Clinical implications of prognostic stratification and molecular subtyping. Poster presentation: SABCS14 #P2-11-23 [Program]
* A distant metastasis-free survival is a temporal measure from a defined start point such as a diagnosis, or treatment of the period to appearance of a distant metastasis. A distant metastasis refers to cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes.
Photo:Massimo Cristofanilli, M.D., FACP, an internationally renowned breast cancer researcher and clinician, Director of the Jefferson Breast Care Center at the Kimmel Cancer Center and Thomas Jefferson University and Hospitals. Photo Courtesy: Jefferson Breast Care Center.
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