MammaPrint is a diagnostic

Diagnosis

Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...

 test used by physicians to assess the risk that a breast tumor

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

 will metastasize

Metastasis

Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 to other parts of the body. This helps physicians determine whether or not each patient will benefit from chemotherapy

Chemotherapy

Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

. MammaPrint is part of the Symphony Suite of breast cancer decision support tests marketed by Agendia.

MammaPrint is based on the Amsterdam 70-gene breast cancer gene signature. It uses fresh tissue for the microarray

Microarray

A microarray is a multiplex lab-on-a-chip. It is a 2D array on a solid substrate that assays large amounts of biological material using high-throughput screening methods.Types of microarrays include:...

 analysis.

In February 2007, the U.S. Food and Drug Administration (FDA) cleared the MammaPrint test for use in the U.S. for lymph node negative breast cancer patients of all ages, ER negative or positive, with tumors of less than 5 cm.

The cost of the assay in the U.S. is $4,200. In Europe, the test costs EUR 2675.

Sampling technique

A tumor sample must be taken with a company-provided punch from an unfixed tumor specimen within an hour of surgery. The sample is then placed in a company-provided perservative, which is then shipped to Agendia.

Clinical trials

Agendia’s 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.

MINDACT Trial

The MINDACT (Microarray In Node negative and 1-3 positive lymph node Disease may Avoid ChemoTherapy) trial is a multi-center, prospective, phase III randomized study comparing the MammaPrint 70-gene expression signature with a common clinical-pathological prognostic tool (Adjuvant! Online) in selecting patients with negative or 1-3 positive nodes for adjuvant chemotherapy in breast cancer.

To date, over 5,942 breast cancer patients have been registered and over 3,142 patients enrolled from 93 participating institutions in 9 European Countries. The goal is to complete enrollment of 6,000 breast cancer patients by late 2011.

In the MINDACT trial, women with breast cancer who are assessed as “High Risk” by both MammaPrint and clinical-pathologic guidelines are advised to have chemotherapy whereas for women with “Low Risk” concordance, hormonal therapy alone is recommended. However, discordant cases are randomized to receive either chemotherapy or hormonal therapy based on clinical-pathological risk assessment or MammaPrint and the patients are followed. It is anticipated that the results of MINDACT will validate MammaPrint as an important prognostic and predictive tool in cancer treatment.

Primary objectives of the MINDACT trial are:

• To confirm that breast cancer patients with a “low risk” molecular prognosis by MammaPrint and “high risk” clinical prognosis can be safely spared chemotherapy without affecting Distant Metastases Free Survival (DMFS).
• To compare anthracycline-based chemotherapy regimens to a docetaxel-capecitabine regimen which may be associated with increased efficacy and reduced long-term toxicities for women with breast cancer.
• To compare the efficacy and safety of 7 years of single agent Letrozole to the sequential strategy of 2 years of Tamoxifen followed by 5 years of Letrozole (Randomization Endocrine therapy).

I-SPY I and I-SPY II

(CALGB 150007/150012 & ACRIN 6657)

Agendia’s MammaPrint signature and its microarray technology are integral components of biomarker analysis and molecular prediction in the landmark National Cancer Institute supported I-SPY I and I-SPY II breast cancer clinical trials which focus on the prediction of therapeutic response in the neoadjuvant setting. The utilization of MammaPrint and Agendia’s whole-genome, microarray platform are anticipated to assist in rapid, focused development of oncologic therapies paired with biomarkers.

Key Objectives of I-SPY breast cancer trials for which the MammaPrint whole-genome microarray is utilized:

• I-SPY I evaluated biomarkers and imaging for predicting response to standard neoadjuvant chemotherapy
• I-SPY II will evaluate Phase 2 drugs in combination with standard chemotherapy in a neoadjuvant setting
• I-SPY II will use biomarkers to stratify patients based on their predicted likelihood of response to treatment