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MAMMAPRINT TEST

What is it?

MammaPrint is a 70-gene microarray test which is used to assess the risk of metastases at an early stage of breast cancer with greater accuracy than is possible using conventional methods. MammaPrint reveals the activity (expression) of 70 specific genes in the tumor sample to indicate a ‘Low Risk’ or ‘High Risk’ profile (no intermediate). The risk of tumor recurrence is determined according to the degree of similarity between the tumor’s gene expression profile and reference profiles.

The test is performed on a tumor biopsy obtained from formalin fixed paraffin embedded (FFPE) tissue by the local pathologist following the test request on this website. The sample is then shipped overnight to Agendia’s  ISO certified laboratory in The Netherlands where the test is performed under an export permit obtained from the South African Department of Health.  In general, results will be available within 10 working days after receiving a tumor biopsy.

When do I recommend it?

To be eligible for a MammaPrint test, a breast cancer patient should fulfill the following international criteria:

  • Tumor size < 5.0 cm
  • Up to 3 positive lymph nodes
  • Stage 1 and Stage 2 invasive breast cancer
  • Estrogen receptor (ER) + or -
  • Tamoxifen independent

The test selection criteria for reimbursement by certain medical schemes in South Africa has been further redefined  following a Health Technology Assessment (HTA) performed in 2009. A prescreen algorithm has been developed and was incorporated into the Gknowmix Database for easy identification of breast cancer patients eligible for testing. An application form with the selection criteria stipulated is provided by some medical schemes. This represents a unique development in the application of pathology supported genetic testing aimed at the exclusion of inappropriate genetic testing.

The 80-gene BluePrint test is generally used together with the 70-gene MammaPrint test for tumour subtyping into four treatment groups: Luminal A, Luminal B, HER2-enriched and basal-like.

Local experience of the MammaPrint service  in routine clinical practice led to the following quotes from opinion leaders in breast cancer:


“Genomics is now an established and frequently used tool in medical research, and particularly in the oncology field.  In breast cancer, genomics has led to a better understanding of the biology and to a molecular reclassification of the disease.” – Dr Rika Pienaar, GVI Oncology, Panorama Hospital, Cape Town, South Africa.


”With the help of MammaPrint many early-stage breast cancer patients can safely forego chemotherapy. This is a major relief to patients with good prognosis as chemotherapy is the most dreaded part of breast cancer therapy.” – Prof  J Apffelstaedt, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa.

 

What are its benefits?

MammaPrint adds a new quality of data to existing prognostic tools as it gives better insight into the biology of the patient’s breast cancer tumor. As the test allows a better distinction to be drawn between high and low-risk patients, it is possible to reduce the number of breast cancer patients who are treated with chemotherapy. This means an improvement in the quality of life of breast cancer patients and substantial cost saving. It helps clinicians to make the best-informed decisions based on a clear risk assessment for the recurrence of distant metastases in breast cancer patients.

European research has revealed that approximately fifty percent of chemotherapy treatments among breast cancer patients are later discovered to have been unnecessary. MammaPrint is available for all lymph node-negative (and 1-3 nodes) breast cancer patients and there is no treatment restriction. If there is a low risk of the patient’s cancer recurring, adjuvant therapy and the toxicity and other side-effects often associated with such treatment may be avoided.

FDA clearance in February 2007 has acted as a positive catalyst for reimbursement by many medical schemes as part of oncology benefits.

Scientific rationale

The high incidence of breast cancer, which kills about 400 000 women worldwide each year, is of special concern in South Africa where more than 4000 women are diagnosed with breast cancer every year. Breast cancer is currently curable in about 70% of patients, but only if it is diagnosed at an early stage and treated adequately.

MammaPrint uses advanced molecular technology (microarray analysis) to predict whether a patient’s breast cancer will metastasize (spread to other parts of a patient's body).

The clinical usefullness of MammaPrint has been validated in more than three independent studies and is a much more accurate prognostic tool than traditional indicators such as NIH, St. Gallen and Adjuvant! Online, which show considerable discordance. Currently approximately 85% of breast cancer patients, identified with traditional prognostic algorithms as being high risk, receive chemotherapy.  MammaPrint  identifies nearly 50% of clinically high-risk patients as low-risk with a good prognosis (and not needing chemotherapy). (Van de Vijver et al. 2002). Prognostication with Mammaprint would therefore, by more accurately defining those who need adjuvant chemotherapy, save approximately 30% of patients with early breast cancer unnecessary chemotherapy.  With the use of the MammaPrint Prescreen Algorithm (MPA) approximately 50% of patients who previously were considered for chemotherapy can now safely avoid this treatment. This was proven with 5-year prospective data in the RASTER trial.

Age when first detected, type of cancer (ER-positive tumors are the most common), nodal status, hormonal treatment with tamoxifen alone or in combination with polychemotherapy and whether or not the ovaries are removed, are all factors which may play a significant role in cancer recurrence and survival. A MammaPrint validation study performed by the TransBIG group showed that each classical feature such as estrogen receptor (ER) status and tumor size loose their significance when compared with the gene profile. There is 30% discordance in ER reading between laboratories worldwide, hence resulting in contradicting outcomes with similar protocols and wrong conclusions. Analytical laboratory test validation for MammaPrint demonstrated greater than 99.9% agreement.

In February 2007 the U.S. Food and Drug Administration approved MammaPrint for clinical use to determine the likelihood of breast cancer recurring within 10 years after a woman's initial diagnosis.  "Clearance of the MammaPrint test marks a step forward in the initiative to bring molecular-based medicine into current practice," said Andrew C. von Eschenbach, M.D., Commissioner of Food and Drugs. "MammaPrint results will provide patients and physicians with more information about the prospects for the outcome of the disease. This information will support treatment decisions.

The costs of unnecessary therapy and dealing with frequent side effects are serious economic considerations. For example, it has been estimated that approximately 60-80% of patients with node-negative breast cancer will be alive 10 years after initial treatment without adjuvant therapy. Even so, up to 58% of patients with node-negative breast cancer may develop recurrent disease and reduction of cancer recurrence in patients has been documented as a result of adjuvant chemotherapy or tamoxifen. In this situation, it becomes crucial to identify patients with node-negative breast cancer at highest risk for recurrence so that they may receive appropriate adjuvant therapy, while patients at lower risk can be spared the toxic effects and unnecessary expenditure can be avoided.

Research and collaboration with Agendia: Gknowmix is the exclusive distributor of MammaPrint® in Southern Africa and signed a collaborative agreement with the University of Stellenbosch, South Africa, to promote genome research innovation. A research protocol has been ethically approved to study the clinical utility of transcriptional profiling in the South African population in comparison with the use of conventional prognostic markers.

Agendia B.V., headquartered in Amsterdam in The Netherlands, provides innovative diagnostic testing for the treatment of cancer patients which is based on gene expression analysis. Agendia was established by researchers from the Netherlands Cancer Institute. MammaPrint® forms a new category of molecular diagnostic test (the In Vitro Diagnostic Multivariate Index Assays (IVDMIA)), and was the first to be approved by the US Food and Drug Administration (FDA) for use in the diagnosis and prognosis of breast cancer. Time Magazine proclaimed MammaPrint® to be one of the best discoveries of 2007 in the area of healthcare.


References

Buyse M, Loi S, van’t Veer L, et al. Validation and Clinical Utility of a 70-Gene Prognostic Signature for Women With Node-Negative Breast Cancer. Journal of the National Cancer Institute, 17, 1183-1192, 2006.

Cleator S and Ashworth A, Molecular profiling of breast cancer: clinical implications. Br J Cancer 90:1120-1124, 2004.

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687–1717.

Kotze MJ, Malan J, Pienaar R, Apffelstaedt J. The role of molecular genetic testing in modern breast health management. SA Fam Pract 2005; 47 (9): 38-40.

Van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999-2009, 2002.

Cardoso F, van't Veer LJ, Bogaerts J, et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl Med 2016; 375(8):717-29. 

Grant KA, Apffelstaedt JP, Wright C, Myburgh E, Pienaar R, de Klerk M, Kotze MJ. MammaPrint Prescreen Algorithm (MPA) reduces chemotherapy in patients with early stage breast cancer. S Afr Med J 2013; 103(8):522-526.






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