Times reporter looks at issues affecting accuracy of different breast cancer tests

Pathologists should consider a recent story about breast cancer testing in the New York Times to be a warning flag, similar to the warning flags that the Coast Guard flies along the coast to warn of an approaching hurricane. The subject of the story was “unclear tests” used to identify whether a breast cancer patient is a candidate for certain therapeutic drugs.

The New York Times story was in response to the public release of new guidelines for processing specimens used in estrogen receptor and progesterone receptor (ER/PR) testing for breast cancer. The guidelines were announced by the College of American Pathologists and American Society of Clinical Oncology (ASCO) on April 19, 2010. One goal of the new guidelines is to improve “the accuracy of immunohistochemistry (IHC) testing for the expression status of estrogen (ER) and progesterone receptors (PgR) in breast cancer” as performed by the hundreds of anatomic pathology laboratories in the United States which perform ER and PR testing.

In the New York Times story, Dr. Linda Griffith was profiled as an individual who “has faced cancer as a doctor and as a patient.” Multiple molecular tests of her breast cancer made it “unclear whether she should receive ‘targeted therapy’.” (Photo by Erik Jacobs for the New York Times.)

In the New York Times story, Dr. Linda Griffith was profiled as an individual who “has faced cancer as a doctor and as a patient.” Multiple molecular tests of her breast cancer made it “unclear whether she should receive ‘targeted therapy’.” (Photo by Erik Jacobs for the New York Times.)

It was the issue of variability in the accuracy of these types of cancer tests that become the centerpiece of the story written by Times reporter Gina Kolata. Under the headline “Cancer Fight: Unclear Tests for New Drug,” Kolata quoted a number of physicians and patients who recognized the problem of inconsistency in the test results produced pathology labs performing HER2/neu LINK, ER, and PR assays. She also interviewed pathologists who acknowledged that the profession was aware of these issues.

Kolata used the issues involved in Herceptin and HER2/neu to illustrate the concerns of physicians, the frustrations of patients, and the challenges for pathologists. Herceptin,  by Genentech,  is one of the so-called targeted therapies. It blocks HER2/neu (Human Epidermal growth factor Receptor 2), a protein associated with an aggressive form of breast cancer, and prevents tumor growth. Furthermore, Herceptin decreases the chance for recurrence by 50%, and it reduces a woman’s chance of dying from breast cancer by 40%.

Herceptin costs $42,000 per year, causes flu-like symptoms and may cause severe heart damage that can be fatal. Therefore, unless a tumor tests for high levels of HER2, it is “a toxic and expensive placebo,” warns Antonio Wolff, M.D., an oncologist at Johns Hopkins specializing in breast cancer, in the same New York Times article.

The problem is that test results for targeted proteins, like HER2/neu, do not achieve the level of accuracy that is assumed and expected by most patients. For example, HER2 tests can give false-positives up to 20% in women who do not need the drug, and false negatives 5% to 10% of the time in women who could benefit from the drug.

Pathologists who do HER2, ER, and PR testing are aware of variable accuracy in results reported by different anatomic pathology labs, Dr. Wolff told Dark Daily, that the status quo may be changing. “Pathologists are taking this issue more seriously than before, and the involvement by their largest organization, CAP, speaks to that.”

It was for these reasons that the American Society of Clinical Oncology and CAP jointly issued new guidelines for testing breast cancer for HER2  and ER/PR last April. CAP has incorporated the new guidelines into its accreditation process.

“I think step one has been done: raise public awareness,” stated Dr. Wolff. “This will hopefully generate momentum so that all players, including health systems and hospitals, realize that resources are needed to allow all healthcare professionals who take care of breast cancer patients to pause, reflect, review their current SOPs (standard operating procedures), and initiate processes to improve standardization of various tests and assays.”

But with Genentech seeking FDA approval for using Herceptin to treat gastric cancer and other targeted therapies in the pipeline, Dr. Wolff observes, “This is an issue that transcends breast cancer. A poorly-developed test is potentially as dangerous as a poorly-developed drug. There are no easy answers and as usual ‘we know the enemy and the enemy is us.’”

Pathologists may find it informative to read the entire story published by the New York Times on April 19, 2010. This news story—and its detailed discussion about the unreliability of certain widely-ordered cancer tests—demonstrates that the integrity, accuracy, and reliability of such tests will undergo increasing public scrutiny. Just as consumer expectations for quality and service have tightened for many products and services in our economy, the same phenomenon will soon occur in anatomic pathology testing.

When one of the nation’s most-read newspapers writes that “…targeted [cancer] therapies are only as good as tests to find their protein targets. And while most patients do not yet know it, those tests can be surprisingly unreliable…” that is a public sign of change. It means that the media is prepared to pay more attention to the accuracy of clinical laboratory and pathology tests that play an important role in determining how patients are to be treated for various types of cancers and other diseases.—P. Kirk

Related Information:

Cancer Fight: Unclear Tests for New Drug

Letter from Elizabeth H. Hammond,M.D.; Daniel F. Hayes, M.D.; and Antonio C. Wolff, M.D., to the New York Times on Breast Cancer Testing

CAP and ASCO Issue Joint Guideline to Improve Hormone Receptor Testing for Patients With Breast Cancer

Dark Daily articles regarding HER2