NYT Examines Challenges To Improving 'Personalized Medicine' For Breast Cancer, Other Diseases

Main Category: Breast Cancer
Also Included In: Genetics;  Pharma Industry / Biotech Industry;  Regulatory Affairs / Drug Approvals
Article Date: 06 Jan 2009 - 3:00 PDT

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The New York Times on Tuesday examined how improvements in genetic testing could affect "personalized medicine" for the treatment of breast cancer and other diseases in the future. Personalized medicine uses genetic screening and other tests to provide physicians with more information to tailor patients' treatments, the Times reports. Experts believe that most drugs currently on the market work for only about half of patients who take them, meaning that "much of the nation's approximately $300 billion annual drug spending [is] wasted," and "countless patients are being exposed unnecessarily to side effects," according to the Times. The Times reports that personalized medicine would "go beyond" the "one-size-fits-all" approach of conventional research studies -- in which the "winning treatment [is] recommended for everybody" -- by determining the best treatments for individual patients, rather than treating all patients the same "in hopes of benefiting the fortunate few." However, there is no universally recognized method for evaluating genetic tests, and many can be marketed without FDA approval.

The Times reports that the breast cancer treatment tamoxifen -- a generic drug used to prevent the recurrence of tumors -- "illustrates the promise and current limitations of genetic testing." A 2003 study led by the Indiana University School of Medicine's David Flockhart demonstrated that tamoxifen is converted through the CYP2D6 enzyme -- also known as 2D6 -- into another substance called endoxifen, which is what actually exerts the cancer-fighting effect. However, the enzyme has different levels of activity in different people because of variations in individuals' 2D6 genes, according to Flockhart. He said that up to 7% of people have an inactive enzyme, depending on their ethnicity, and an additional 20% to 40% have a modestly active enzyme. For these individuals, tamoxifen would offer little or no protection against tumors because the patients' bodies could not convert the drug into endoxifen. Currently, most US patients are treated with aromatase inhibitors -- a more expensive, newer class of drugs that cost about $18,000 over five years, compared with $500 for tamoxifen. Aromatase inhibitors performed better than tamoxifen in clinical trials conducted "before the role of 2D6 was generally understood," the Times reports. However, those trials might have found that tamoxifen worked as well or better than the newer drugs if only women with active 2D6 were included, according to researchers at the Dana-Faber Cancer Institute.

The Times reports that "proving these suppositions and having them incorporated into medical practice have not been easy." Tests are available to detect the 2D6 genes of individual patients for about $300, but many experts are hesitant to use the tests because of conflicting study results examining the relationship between tamoxifen and the genes. In addition, there are dozens of variants of the 2D6 gene, and laboratories can differ in how they interpret test results. There also are no clear guidelines for how doctors should act upon the information provided by the test. Drug maker Genentech has petitioned FDA to regulate the tests, and the agency in a meeting last month said that clinical trials would be the best way to validate the tests. However, developers of the tests say that new trials would be too expensive and time-consuming, "so many tests are validated by reanalyzing patient data from old trials," the Times reports. For example, a 2005 study by Matthew Goetz and colleagues at the Mayo Clinic analyzed stored tumor samples from an old trial of breast cancer patients to test the 2D6 genes of each patient. The study found that 32% of women with inactive 2D6 enzymes had relapsed or died within two years, compared with only 2% of women with active enzymes.

Experts also point to other "formidable obstacles on the path to the promised land of personalized medicine," according to the Times. The ability of test developers to prove that their tests are accurate and useful is one major obstacle. Other obstacles include the reluctance of drugmakers to encourage or develop tests that could limit the use of their drugs and the possibility that insurers might not pay for the tests. However, drugmakers are "starting to realize that their medicines might not be approved for paid or without better evidence that they work," according to the Times (Pollack, New York Times, 12/30/08).

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