Mammaprint is a test that identifies a profile of a tumor sample that is then used to assess risk. In February 2005, the BlueCross BlueShield Association Technology Evaluation Center (TEC) conducted a technology assessment on gene expression profiling for managing breast cancer treatment. The TEC Assessment summarized the evidence for four different gene expression profiling assays, in various stages of development, that are intended for eventual use in identifying those patients at low risk of recurrence for whom adjuvant chemotherapy can be avoided. The four assays were the 21-gene Oncotype DX (Genomic Health), the 70-gene MammaPrint® (Agendia; also referred to as the “Amsterdam signature”), the 76-gene “Rotterdam signature” (Veridex), and a 41-gene signature reported by Ahr and colleagues. Because current selection methods by traditional clinical and histopathological criteria exclude only a small proportion from adjuvant chemotherapy, and only a small proportion derive significant benefit, it is likely that a significant number of women could avoid the side effects of chemotherapy if more accurate selection methods were available. However, the TEC Assessment concluded that because published evidence supporting clinical utility is not available, the evidence for all of the gene expression panels is insufficient to permit conclusions concerning the effect of gene expression profiling on selecting patients who do not need chemotherapy for the purpose of avoiding adverse outcomes, while maintaining or improving disease-free or overall survival outcomes.by Paik and colleagues discussed above.
Since then, NCCN has recommended Oncotype but not Mammaprint. There is evidence that Mammaprint as compared to NCCN guidelines identifies only 66% of patients as being in a good prognostic group, which may or may not be detrimental. The two tests are not identical and Oncotype recommendation by NCCN does not translate into an approval for Mammaprint, as per CTAF, California Tech Assessment Forum(http://www.gopathdx.com/?action-model-name-research-itemid-13) and Medicare(http://palmettogba.com/palmetto/providers.nsf/DocsCat/Providers~Jurisdiction%201%20Part%20B~Articles~General~7WLQ5C4784?open&navmenu=Articles%7C%7C%7C%7C). CTAF reaffirmed its recommendation in June, 2010: “It is recommended that the use of the 70-gene prognostic signature (MammaPrint) does not meet Technology Assessment Criterion 3 through 5 for safety, effectiveness and improvement in health outcomes.
On the other hand, MammaPrint was added to the St. Gallen’s International Oncology Guidelines for Primary Therapy of Early Breast Cancer(Goldhirsch 2009) and in 2008 MammaPrint was included in The Dutch Institute for Healthcare Improvement CBO Guidelines. The CBO guidelines, drafted in collaboration with the Dutch Association of Comprehensive Cancer Centers (ACCC) and the Dutch National Breast Cancer Consultation Group (NABON). MammaPrint will be offered as standard of care for all eligible early stage breast cancer patients at the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL). In an important change from the previous St Gallen conference and after a long debate, the Panel supported the use of a validated multigene-profiling assay, if readily available, as an adjunct to high-quality phenotyping of breast cancer in cases in which the indication for adjuvant chemotherapy remained uncertain.
Most recently, Hayes Annual Review of MammaPrint® for Prognosis of Breast Cancer Recurrence on June 10, 2013concluded that: “There are some new published studies on this technology. However, our review of the abstracts indicates that the results of these studies will not change the conclusions or ratings in the existing Hayes report (which did not recommend it).
In 2016, Cardoso published supportive data for Mammaprint. He concluded that Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. Nevertheless, these results were not widely adopted in the USA and Mammaprint is not considered med necessary in the USA.
Goldhirsch et al, Thresholds for therapies: highlights of the St Gallen International …… Annals of Oncology 20:1319-29, 2009.
F. A. de Snoo, M. Knauer, R. A. Bender, L. Stork-Sloots, E. J. Rutgers, A. M. Glas, S. C. Linn, L. J. Van ‘t VeerJ Outcome prediction by the 70-gene profile in the context of the National Comprehensive Cancer Network (NCCN) guidelines. J Clin Oncol 27:15s, 2009 (suppl; abstr 535)
2007 TEC Assessment: Gene expression profiling for managing breast cancer treatment. www.bcbs.com/tec/vol20/20_03.html
National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Breast Cancer. http://nccn.org/professionals/physician_gls/PDF/breast.pdf, 2018
Fatima Cardoso, M.D., Laura J. van’t Veer, Ph.D., Jan Bogaerts, Ph.D., Leen Slaets, Ph.D., Giuseppe Viale, M.D., Suzette Delaloge, M.D., Jean-Yves Pierga, M.D., Ph.D., Etienne Brain, M.D., Ph.D., Sylvain Causeret, M.D., Mauro DeLorenzi, Ph.D., Annuska M. Glas, Ph.D., Vassilis Golfinopoulos, M.D., Ph.D., Theodora Goulioti, M.D., Susan Knox, M.A., Erika Matos, M.D., Bart Meulemans, M.Sc., Peter A. Neijenhuis, M.D., Ulrike Nitz, M.D., Ph.D., Rodolfo Passalacqua, M.D., Peter Ravdin, M.D., Isabel T. Rubio, M.D., Mahasti Saghatchian, M.D., Tineke J. Smilde, M.D., Ph.D., Christos Sotiriou, M.D., Ph.D., Lisette Stork, M.Sc., Carolyn Straehle, Ph.D., Geraldine Thomas, Ph.D., Alastair M. Thompson, M.D., Jacobus M. van der Hoeven, M.D., Ph.D., Peter Vuylsteke, M.D., René Bernards, Ph.D., Konstantinos Tryfonidis, M.D., Emiel Rutgers, M.D., Ph.D., and Martine Piccart, M.D., Ph.D., for the MINDACT Investigators,70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer
N Engl J Med 2016; 375:717-729