Genetic Detection of a Predisposition for Breast Cancer- US Patent No. 6,033,857

By: Charles Dresser

A Cruel Reality in Breast Cancer Statistics

One in eight American women will get breast cancer in their lifetime according to the American Cancer Society. Treatment of late-stage breast cancer, as with many other cancers, is often performed with a low-likelihood for success and when successful is often disfiguring. Early diagnosis of breast cancer is, therefore, very important for its treatment. An advance in genetic science, described in US Pat. No. 6,033,857 allows women to learn of their genetic susceptibility before they ever get cancer.

It has long been known that susceptibility to breast cancer is hereditary. A team at Myriad Genetics found that mutations occurring within a specific gene, BRCA2, indicate an increased susceptibility to breast cancer. Interestingly, the Myriad Genetics team did this in part with the help of large Utah families.

The Genetic Culprit

Earlier work had suggested that a genetic locus of 1 – 1.5 million base pairs of DNA located on human chromosome number 13 is related to an increased susceptibility to breast cancer. By using genetic information from many family members in large Utah families, the Myriad team was able to achieve a greater statistical power in their experiments. Genetic information from many brothers and sisters (i.e., sibships) was correlated with their known breast cancer histories. As a result, the genetic sequence that correlated with an increased probability of developing breast cancer (and likely contained the BRCA2 gene) was made smaller. Mapping continued in an iterative process, as more genetic information from more families was analyzed, until the BRCA2 gene itself was specifically localized. Out of the 1 – 1.5 million base pairs originally investigated, the BRCA2 gene was found to comprise just 1,185 base pairs. Once the BRCA2 gene was mapped its effects on breast cancer were better understood.

Presence of a mutated form (i.e., mutant allele) of the BRCA2 gene was found to correlate to an increased risk of breast cancer. Also, a mutated BRCA2 protein (the result of expression of a mutated BRCA2 gene) was found present in cancerous breast tumors believed to be originating from BRCA2 dysfunction. Additionally, when only a normal form (i.e., wild-type allele) of the BRCA2 gene was present, no cancer originating from the BRCA2 protein was observed. It is therefore believed that the BRCA2 gene is a tumor suppressive gene, and that breast cancer results when mutations of the BRCA2 gene cause significant dysfunction during the gene’s expression.

A Brighter Outlook Through Innovation

With this information, the Myriad team was able to develop test methods and products that compare an individual’s BRCA2 gene with the wild-type allele of the BRCA2 gene. These products are similar to those used for genetic testing in other areas but are tailored for BRCA2.

Using these products, doctors can now test an individual to determine if she carries a mutated form of the BRCA2 gene. Since the time of this invention more has been learned about the BRCA2 gene. The National Breast Cancer Foundation now recognizes that women with a BRCA2 gene mutation are up to 65% more likely than women without the mutation to be diagnosed with breast cancer before the age of 70. Testing for BRCA2 gene mutations now allows women (and men) with a family history of breast cancer to know, while still healthy, if they are at an elevated-risk of developing breast cancer. Those who test positive for the BRCA2 mutations may choose to undergo preventative surgery or commence early detection plans (that include more regular breast cancer screenings beginning at an earlier age). Additionally, knowledge that a developed breast cancer has resulted from a BRCA2 mutation allows the use of targeted therapeutics. As a result of the Myriad team’s efforts and the large families they studied, doctors and patients today are better prepared to prevent and when necessary, treat BRCA2 mutation-mediated breast cancer.