'Genetic Profiling' To Revolutionize Breast Cancer Treatment

Physicians Will Tailor Therapies To Individual Women

The face of breast cancer treatment is poised to get a new look as physicians enhance a system known as "genetic profiling."

It is a new way to predict the course of the disease, and add to the knowledge about which women will require aggressive treatment for long-term survival. It could also revolutionize treatment of all cancers.

In a study published in the medical journal The Lancet, a team of Duke University researchers, working with experts from the Koo Foundation Sun Yat-Sen Cancer Center in Taipei, China, offer the strongest evidence yet the system works, showing a 90 percent accuracy rate.

"Our model is the clearest example to date of a step toward personalized medicine," study author Dr. Erich Huang says.

Profiling Technology Matures

Genetic profiling is a way of analyzing a breast cancer patient's basic cell information to develop "genetic signatures" that can ultimately be used to define risk levels of disease.

In this study, the Duke team used a new type of gene-chip technology to closely examine the genetic comings and goings of cells in the tumors of breast cancer patients.

Then, applying a sophisticated method of statistical analysis, the researchers were able to generate a DNA "genetic signature" for each patient. Using that information they could predict - with 90 percent accuracy - the aggressive status of a breast cancer tumor, and whether a cancer was likely to recur.

Currently, removing and testing the lymph nodes - cells that surround the breast - is the only method available to assess a woman's long-term cancer profile and her current treatment needs. The condition of the lymph nodes are believed to be critical in determining long-term survival rates, since cancers that spread to these cells are thought to be more aggressive.

However, experts say it is not uncommon to find women with few or no cancerous lymph nodes whose disease recurs in just a few years, or those with extremely aggressive lymph node profiles who are effectively cured in just one course of treatment.

The genetic profiling system, the researchers say, will give a far more accurate prognosis and help physicians know from the start which women are likely to benefit from treatments such as chemotherapy and radiation, and which women can safely skip these regimens without compromising their future health.

For Dr. Harry Ostrer, director of the Human Genetics Program at New York University Medical Center, the new study validates earlier findings with yet more evidence that genetic profiling has a strong role in the future of cancer treatment.

"This study was well-executed and it definitely represents the direction in which we are going - genetic profiling is something with a foreseeable clinical future," Dr. Ostrer says.

Physicians Will Add Profiling Soon

Because clinical trials are already under way using various methods of gene profiling, Dr. Ostrer predicts that within five years or less the system will become part of every cancer patient's diagnostic regimen.

"It's very close to clinical application, and I think it will play a major role in determining the course of an individual's choice of cancer treatments, not only in respect to breast cancer, but all cancers," says Dr. Ostrer.

The new study involved 89 breast cancer patients, each of whom underwent tumor removal and subsequent biopsies of the lymph nodes. Simultaneously, they had genetic profiling.

The scientists then compared their genetic findings, and predictions, with the actual medical records that documented, in detail, the course of each woman's disease and all post surgical follow-up diagnosis and care.

The final result: The predictions made by the genetic profiling at the time of surgery were 90 percent accurate in determining the course of each woman's disease. This included predicting recurrences that, in many instances, did not develop until years after initial treatment.

Although previous research has been conducted on genetic profiling, with similar results, the Duke study was unique in that it used large collections of gene patterns to determine findings, something the researchers believe leads to a higher level of accuracy.

Still, the Duke researchers say they will not be satisfied until accuracy is closer to 100 percent, something they hope to accomplish in the near future as their methods of analysis are refined.

If genetic profiling does become widely available as a test, experts estimate that, at least initially, the cost will be about $2,000 per patient. That cost will likely be compared to the cost of routine chemotherapy and radiation, which genetic profiling may help many cancer patients avoid.

Always consult your physician for more information.

What Is a Sentinel Lymph Node Biopsy?

A sentinel lymph node biopsy is a procedure that involves injecting a dye and/or radioactive substance near the tumor. This injection helps to locate the lymph node closest to the tumor (sentinel node); the one that is most likely to have cancer cells present if the cancer has spread.

The surgeon removes the lymph node that absorbs the dye and radioactive substance and sends it to the pathologist to examine it closely for the presence of cancer cells. Cancer cells may appear first in the sentinel node before spreading to other parts of the body.

Always consult your physician for more information.

Statistics on Breast Cancer

Breast cancer is the most common cancer among women, excluding non-melanoma skin cancer. Currently, approximately 3 million women in the US are living with the disease, including 2 million who have already been diagnosed, and another 1 million who do not yet know they have the disease.

American Cancer Society (ACS) estimates for 2003 include 211,300 new cases of invasive breast cancer being diagnosed in the US. In addition, ductal carcinoma in situ will be responsible for 55,700 new cases this year.

Year 2003 estimates include 40,200 deaths occurring from breast cancer in the US alone - this includes approximately 39,800 women and 400 men.

Breast cancer is the leading cause of cancer death among women between the ages of 20 and 59 in the US, and the leading cause of cancer death among women worldwide.

Online Resources  

American Cancer Society

Breast Cancer Prevention Trial

Gene Clinics and Gene Tests

National Cancer Institute (NCI)

National Human Genome Research Institute

National Institutes of Health (NIH)

National Women's Health Information Center

• 20 percent to 40 percent are due to mutations in the BRCA1 gene
• 10 percent to 30 percent are due to mutations in the BRCA2 gene
• <1 percent are due to mutations in the P53 gene
• <1 percent are due to mutations in the PTEN gene
• 30 percent to 70 percent are due to other genes

In 1990, DNA linkage studies on large families with the above characteristics identified the first gene associated with breast cancer. Scientists named this gene “breast cancer 1” or BRCA1 (pronounced brak-uh). BRCA1 is located on chromosome 17. Mutations in the gene are transmitted in an autosomal dominant pattern in a family.

Since it was clear that not all breast cancer families were linked to BRCA1, studies continued and in 1994, scientists discovered another gene (similar to BRCA1), and named it BRCA2. BRCA2 is located on chromosome 13. Mutations in this gene are also transmitted in an autosomal dominant pattern in a family.

Both BRCA1 and BRCA2 are tumor suppressor genes that usually have the job of controlling cell growth and cell death.

Everyone has two BRCA1 (one on each chromosome #17) and two BRCA2 genes (one on each chromosome #13). When a person has one altered or mutated copy of either the BRCA1 or BRCA2 gene, their risk for various types of cancer increases.

What Is Hereditary Breast Ovarian Cancer (HBOC) Syndrome?

Hereditary breast ovarian cancer (HBOC) syndrome is characterized by the following features in a family:

• an early age of onset of breast cancer (often before age 50)
• family history of both breast and ovarian cancer
• increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently) or an individual with both breast and ovarian cancer
• an autosomal dominant pattern of inheritance (vertical transmission through either the mother or father’s side of the family)
• an increased incidence of tumors of other specific organs, such as the prostate
  

Other factors that increase the chance that a family has the hereditary breast ovarian cancer syndrome include:

• family history of male breast cancer
• Ashkenazi Jewish ancestry

Both copies of a tumor suppressor gene must be altered or mutated before a person will develop cancer.

In HBOC, the first mutation is inherited from either the mother or father and is therefore present in all cells of the body. This is called a germline mutation. Whether a person who has a germline mutation will develop cancer and where the cancer(s) will develop depends upon where (which cell type) the second mutation occurs.

Some individuals who have inherited a germline BRCA1 or BRCA2 mutation never develop cancer because they never get the second mutation necessary to knock out the function of the gene and start the process of tumor formation.

This can make the cancer appear to skip generations in a family, when, in reality, the mutation is present. Persons with a mutation, regardless of whether they develop cancer, however, have a 50/50 chance to pass the mutation on to the next generation.

It is also important to remember that the BRCA1 and BRCA2 genes are not located on the sex chromosomes. Therefore, mutations can be inherited from the mother or the father’s side of the family.

Always consult your physician for more information.