Symphony (Agendia)

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Symphony is a suite of assays that analyze hundreds of genes in an individual breast cancer. The test is marketed by Agendia. The results aid physicians in deciding appropriate treatment for each patient.

An assay is an investigative (analytic) procedure in laboratory medicine, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a target entity. The analyte can be a drug, a biochemical substance, or a cell in an organism or organic sample. The measured entity is generally called the analyte, the measurand or the target of the assay. The assay usually aims to measure an intensive property of the analyte and express it in the relevant measurement unit.

Breast cancer cancer that originates in the mammary gland

Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin.

There are four breast cancer tests within the Symphony suite:

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.

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Trastuzumab pharmaceutical drug

Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer. Specifically it is used for breast cancer that is HER2 receptor positive. It may be used by itself or together with other chemotherapy medication. Trastuzumab is given by slow injection into a vein and injection just under the skin.

Gefitinib chemical compound

Gefitinib (ZD1839) is a drug used for certain breast, lung and other cancers. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor (EGFR) in target cells. Therefore, it is only effective in cancers with mutated and overactive EGFR. It is marketed by AstraZeneca and Teva.

Desmoplastic small-round-cell tumor

Desmoplastic small-round-cell tumor is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones.

Targeted therapy

Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.

Adjuvant therapy, also known as adjunct therapy, add-on therapy, and adjuvant care, is therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments. An example of such adjuvant therapy is the additional treatment usually given after surgery where all detectable disease has been removed, but where there remains a statistical risk of relapse due to the presence of undetected disease. If known disease is left behind following surgery, then further treatment is not technically adjuvant.

A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combination chemotherapy. The majority of drugs used in cancer chemotherapy are cytostatic, many via cytotoxicity.

Sunitinib chemical compound

Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.

Lapatinib chemical compound

Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is used in combination therapy for HER2-positive breast cancer. It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).

Hormonal therapy in oncology is hormone therapy for cancer and is one of the major modalities of medical oncology, others being cytotoxic chemotherapy and targeted therapy (biotherapeutics). It involves the manipulation of the endocrine system through exogenous or external administration of specific hormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones. Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergo cell death. Surgical removal of endocrine organs, such as orchiectomy and oophorectomy can also be employed as a form of hormonal therapy.

Triple-negative breast cancer refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) and HER2/neu. This makes it more difficult to treat since most hormone therapies target one of the three receptors, so triple-negative cancers often require combination therapies. Triple negative is sometimes used as a surrogate term for basal-like; however, more detailed classification may provide better guidance for treatment and better estimates for prognosis.

Breast cancer management takes different approaches depending on physical and biological characteristics of the disease, as well as the age, over-all health and personal preferences of the patient. Treatment types can be classified into local therapy and systemic treatment. Local therapy is most efficacious in early stage breast cancer, while systemic therapy is generally justified in advanced and metastatic disease, or in diseases with specific phenotypes.

Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is present, as demonstrated by laboratory testing, radiologic testing, or clinically. Similarly, "disease-free survival" is when patients have had operations and are left with no detectable disease.

Breast cancer classification divides breast cancer into categories according to different schemes criteria and serving a different purpose. The major categories are the histopathological type, the grade of the tumor, the stage of the tumor, and the expression of proteins and genes. As knowledge of cancer cell biology develops these classifications are updated.

Metastatic breast cancer

Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumours, secondaries or stage 4 breast cancer, is a stage of breast cancer where the disease has spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer. There is no stage after IV.

Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy and synthetic lethality. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient. A number of experimental cancer treatments are also under development. Under current estimates, two in five people will have cancer at some point in their lifetime.

A CDK inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells. The US FDA approved the first drug of this type, palbociclib (Ibrance), a CDK4/6 inhibitor, in February 2015, for use in postmenopausal women with breast cancer that is estrogen receptor positive and HER2 negative. Several compounds are in clinical trials.

DirectHit is a pharmacodiagnostic test used to determine the tumor sensitivity or resistance to drug regimens recommended for the treatment of breast cancer by the National Comprehensive Cancer Network. It is a noninvasive test performed on small amounts of tissue removed during the original surgery lumpectomy, mastectomy, or core biopsy. DirectHit was developed by CCC Diagnostics Inc., a biotechnology company established by former researchers from Johns Hopkins University. DirectHit was launched on 14 January 2010. Currently, it is the only available test for predicting treatment outcomes for anticancer chemotherapy drugs for breast cancer.

Nintedanib chemical compound

Nintedanib, marketed under the brand names Ofev and Vargatef, is an oral medication used for the treatment of idiopathic pulmonary fibrosis and along with other medications for some types of non-small-cell lung cancer.

An adaptive clinical trial is a clinical trial that evaluates a medical device or treatment by observing participant outcomes on a prescribed schedule, and modifying parameters of the trial protocol in accord with those observations. The adaptation process generally continues throughout the trial, as prescribed in the trial protocol. Modifications may include dosage, sample size, drug undergoing trial, patient selection criteria and "cocktail" mix. In some cases, trials have become an ongoing process that regularly adds and drops therapies and patient groups as more information is gained. Importantly, the trial protocol is set before the trial begins; the protocol pre-specifies the adaptation schedule and processes.

References

  1. Roepman P, Horlings HM, (2009) “Microarray-Based Determination of Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Status in Breast Cancer” Clin Cancer Res. 15(22):7003–11
  2. Introducing BluePrint™: A Molecular Subtyping Profile for Breast Cancer