МаммоПринт: Геномный тест для прогноза рецидива рака молочной железы.

MammaPrint is a prognostic and predictive diagnostic test for early stage breast cancer patients that assess the risk that a tumor will metastasize to other parts of the body. It gives a binary result, high risk or low risk classification, and helps physicians determine whether or not a patient will benefit from chemotherapy. Women with a low risk result can safely forego chemotherapy without decreasing likelihood of disease free survival. MammaPrint is part of the personalized medicine portfolio marketed by Agendia. MammaPrint is based on the Amsterdam 70 gene breast cancer gene signature and uses formalin fixed paraffin embedded (FFPE) or fresh tissue for microarray analysis. It is a laboratory developed test (LDT) which falls into the class of In Vitro Diagnostic Multivariate Index Assays (IVDMIA). MammaPrint was the first (2007) IVDMIA to be cleared by the Food and Drug Administration (FDA) in a De Novo Classification Process (Evaluation of Automatic Class III Designation) and is the only molecular diagnostic test with a randomized prospective clinical trial validating clinical utility. The test uses RNA isolated from tumor samples and run on custom glass microarray slides in order to determine the expression of a 70 gene signature. The expression profile is then used in a proprietary algorithm to categorically classify the patient as being at either high or low risk of breast cancer recurrence. MammaPrint has been prospectively, clinically validated for use in early stage (I and II) breast cancer patients regardless of estrogen receptor (ER) or Human Epidermal Growth Factor Receptor 2 (HER2) status, with a tumor size ≤ 5.0 cm, and 0 3 positive lymph nodes (LN0 1), with no special specifications for N1mi pathology. This differentiates MammaPrint from other multi gene assays in use today that have only shown predictive value in ER positive, HER2 negative, lymph node (LN) negative patients. MammaPrint is also indicated for patients with ER negative tumors (15% of tumors). There are no exclusion criteria based on histopathologic tumor type (i. e. ductal, lobular, mixed, etc.) or age. MammaPrint is predictive for pre and post menopausal women.

The Human Genome Project identified approximately 25,000 genes in the human genome and created the possibility for personalized medicine. The Netherlands Cancer Institute (NKI) in Amsterdam utilized this information and applied it specifically to breast cancer, creating the Amsterdam 70 gene signature (70 GS). MammaPrint is the commercialized assay that measures the 70 GS. The NKI hypothesized that breast cancer is a genetic, heterogeneous disease, where gene expression would be different in aggressive breast tumors that develop recurrences following surgery than from those that are less aggressive and do not recur or spread throughout the body. To identify a novel and independent predictor of breast cancer recurrence, DNA microarray technology was used to interrogate all 25,000 genes in untreated tumor samples from women where follow up categorized them as being disease free or having distant metastases within five years. Supervised classification identified significantly different expression patterns in 70 genes that were strongly predictive of a short interval to distant metastases.

The paradigm used to development the 70 GS makes it unique in molecular breast cancer diagnostics because it allowed the tumor biology itself to show the genes most predictive of known patient outcomes. Rather than pre selecting a few genes based on literature and known information at a given time, supervised learning from the entire expressed genome gives it farsighted utility as the knowledge of cancer biology evolves. Furthermore, development using untreated tumors allows physicians to know their patient's risk of recurrence, without any treatment bias or assumptions, before making a patient's treatment plan.

Molecular diagnostics are used in combination with traditional clinicopathologic factors to decide on a treatment plan. MammaPrint provides a binary result, either high risk or low risk. Patients with a low risk result are unlikely to develop distant metastases and are therefore unlikely to benefit from chemotherapy. Since many breast cancers are considered genomically low risk independent from clinicopathology, a significant number of patients can be saved from overtreatment with chemotherapy.

The cost of the assay in the U. S. is $4,200. In Europe, the test costs EUR 2675. Several studies show that the use of the MammaPrint is cost effective for patients in the United States, Europe, Canada and Japan by providing additional information to help doctors tailor treatment to the individual patient. MammaPrint provides definitive results and does not have an intermediate category, making it more cost effective than other breast cancer risk assays available.

MammaPrint is the only commercially available breast cancer molecular diagnostic assay to achieve level 1A evidence. Other extensive clinical trials and research collaborations have produced numerous retrospective and prospective validation studies over the past decade which have enabled the successful commercialization of genomic microarray assays, such as the FDA cleared 70 gene MammaPrint profile. Large, multi institutional clinical trials, such as MINDACT and ISPY 2, are assessing MammaPrint.