Office of Technology Development

Novel Method for Assessing Risk of Breast Cancer Metastasis

SK1557

Summary of Invention

A genome-wide analysis to characterize the methylomes of breast cancers identified a link between breast cancer methylomes and metastatic potential. Further, MSKCC investigators determined the methylome signatures in specific subsets of breast cancers and developed a clinical test that can predict the aggressiveness of a tumor and the risk of metastasis in a breast cancer patient. This set of genes can be assayed using either PCR or mass spectrometry. The test utilizes tumor DNA (either paraffin-embedded or frozen) from the patient and involves relatively simple, clinically practicable methods. Assessing the methylome of a tumor can help direct physicians towards more aggressive therapy for patients likely to develop metastasis while sparing patients at low risk for metastasis from unnecessary measures. The marker sets are particularly applicable to methods and kits for use in connection with human breast cancer, colon cancer, and glioma.

Background

Instructions encoded by DNA and carried out by the cell are dictated both by DNA sequence information and by epigenetic (non-base pair) changes to the DNA. These epigenetic changes to DNA include methylation of specific bases. Cancer-specific alterations in DNA methylation are hallmarks of human malignancies. However, the nature of the breast cancer epigenome and its effects on metastatic behavior remained obscure. Dr. Timothy A. Chan and his colleagues have now shown that the methylome of breast cancer establishes a foundation for assessing the risk of metastasis.

Advantages

This method:

utilizes patient DNA rather than RNA, as is the case with the current leading biomarker panel;
serves as an accurate predictor of survival in conjunction with known biomarkers; and
can be used in patients with early-stage breast cancer.

Market Need

An estimated 207,000 breast cancer cases were diagnosed during 2010 alone. In roughly 60% of breast cancer diagnoses, cancer is confined to the primary site, and, in about 33%, cancer has spread no further than the regional lymph nodes. Therefore there is a clear need for a relatively simple prognostic test that assesses metastatic potential in the approximately 192,500 breast cancer patients diagnosed annually with locoregional disease. Current mRNA-based expression analysis methods have significant limitations, and there is a need in the market for more accurate prognostic tools.

Areas of Application

Breast cancer prognosis

Lead Inventor

Timothy A. Chan, MD, PhD

Patent Information

U.S. PCT application pending

Stage of Development

Retrospective Clinical Studies complete

Contact Information

Yashodhara Dash, MBBS, PhD, MBA
Licensing Manager
Tel: 212-639-6181; Fax: 212-717-3439
E-mail: dashy@mskcc.org

Categories

Diagnostics

aggressive (uh-GREH-siv)

In medicine, describes a tumor or disease that forms, grows, or spreads quickly. It may also describe treatment that is more severe or intense than usual.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

analysis (uh-NA-lih-sis)

A process in which anything complex is separated into simple or less complex parts.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

biomarker (BY-oh-MAR-ker)

A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Also called molecular marker and signature molecule.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

breast (brest)

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

breast cancer (brest KAN-ser)

Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

cell (sel)

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

clinical (KLIH-nih-kul)

Having to do with the examination and treatment of patients.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

colon (KOH-lun)

The longest part of the large intestine, which is a tube-like organ connected to the small intestine at one end and the anus at the other. The colon removes water and some nutrients and electrolytes from partially digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

DNA

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

early-stage breast cancer (ER-lee-stayj brest KAN-ser)

Breast cancer that has not spread beyond the breast or the axillary lymph nodes. This includes ductal carcinoma in situ and stage I, stage IIA, stage IIB, and stage IIIA breast cancers.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

glioma (glee-OH-muh)

A cancer of the brain that begins in glial cells (cells that surround and support nerve cells).

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

lymph (limf)

The clear fluid that travels through the lymphatic system and carries cells that help fight infections and other diseases. Also called lymphatic fluid.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

marker (MAR-ker)

A diagnostic indication that disease may develop.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

mass (mas)

In medicine, a lump in the body. It may be caused by the abnormal growth of cells, a cyst, hormonal changes, or an immune reaction. A mass may be benign (not cancer) or malignant (cancer).

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

metastasis (meh-TAS-tuh-sis)

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

metastatic (meh-tuh-STA-tik)

Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

methylation (MEH-thuh-LAY-shun)

A chemical reaction in which a small molecule called a methyl group is added to other molecules. Methylation of proteins or nucleic acids may affect how they act in the body.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

PCR

A laboratory method used to make many copies of a specific DNA sequence. Also called polymerase chain reaction.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

regional (REE-juh-nul)

In oncology, describes the body area right around a tumor.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

retrospective (REH-troh-SPEK-tiv)

Looking back at events that have already taken place.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

RNA

One of two types of nucleic acid made by cells. RNA contains information that has been copied from DNA (the other type of nucleic acid). Cells make several different forms of RNA, and each form has a specific job in the cell. Many forms of RNA have functions related to making proteins. RNA is also the genetic material of some viruses instead of DNA. RNA can be made in the laboratory and used in research studies. Also called ribonucleic acid.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

significant (sig-NIH-fih-kunt)

In statistics, describes a mathematical measure of difference between groups. The difference is said to be significant if it is greater than what might be expected to happen by chance alone. Also called statistically significant.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

therapy (THAYR-uh-pee)

Treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

tumor (TOO-mer)

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)