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Leading Provider Groups Set Guidelines for Hormone Receptor Testing

April 23, 2010

Written By Janine E. Guglielmino, MA, Senior Director, Programs and Partnerships & Yarissa Reyes

Two provider organizations issued a joint guideline on April 19 to help doctors assess the hormone receptor status of newly diagnosed breast cancers.

The guidelines, from the College of American Pathologists (CAP) and the American Society of Clinical Oncology (ASCO), aim to improve accuracy of the immunohistochemical (IHC) tests used to measure the estrogen and progesterone sensitivity of breast cancers.

The organizations moved to establish guidelines after finding that up to 20 percent of IHC tests give inaccurate results, either as false negatives (cancers that test negative for hormone receptors but are truly positive) or false positives (cancers that test positive for hormone receptors but are actually negative).

The guidelines address two separate and important issues, "one, of poor quality testing, and two, that biology is not always straightforward," said Eric P. Winer, MD, director of the breast oncology center at Dana-Farber Cancer Institute and a member of LBBC’s Medical Advisory Board.

These rules will help standardize the lab procedures and interpretations that if done poorly can lead to inconclusive or inaccurate results, Dr. Winer said.

Background of the Guidelines

Doctors began regularly using IHC tests in the early 1990s to determine the percentage of estrogen (ER) and progesterone (PR) receptors on cancer cells. Many versions of the IHC test are available, and no central lab exists to analyze results.

As cancer treatment becomes more personalized, the accuracy of IHC and other tests grows in importance. These tests play a central role in selecting the therapies most likely to extend life; they also help women avoid the side effects and financial costs of inappropriate treatments. IHC findings predict whether cancers are likely to respond to hormonal therapies like Tamoxifen and Aromatase Inhibitors.

CAP and ASCO previously wrote a guideline for HER2 testing . In 2008 the groups gathered again to establish guidelines for hormone-sensitive breast cancers, which make up about two-thirds of cases. An international panel of experts found that up to 1 in 5 IHC tests gave inaccurate results, mostly because of differences in how facilities collect and transport tissue samples and how they interpret findings.

What the Guidelines Say

The panel recommended that:

  • An IHC test for ER and PR status be performed on all newly diagnosed invasive breast cancers. When possible, recurrences should be tested to verify initial results and make sure the cancer’s hormone status did not change.
  • Labs that create their own IHC tests should validate (check) their results against tests that were proved reliable in previous studies. When compared against the proven test, ER/PR positive results should agree 90 percent of the time; ER/PR negative ones, 95 percent of the time.
  • IHC test results should report the percentage of the cancer that tested hormone positive, the quality of the test itself, the handling of tissue samples and the interpretation of findings.
  • Facilities should regularly compare findings from IHC tests on cancerous tissue to those performed on healthy breast tissue (a control).
  • Any IHC test that shows 1 percent or more ER or PR positive cells should be considered hormone sensitive. Clinical trials have shown that people whose cancers are "weakly positive"—between 1 percent and 10 percent hormone positive—still benefit from hormonal therapy.

These guidelines apply to invasive breast cancers, but IHC tests are also performed in ductal carcinoma in situ (DCIS), a noninvasive, stage 0 breast cancer. The panel made no formal recommendations for DCIS but suggested women should speak with their doctors.

What These Guidelines Mean for You

A federal law requires facilities to follow the new guidelines. CAP and ASCO will train providers on the rules, and CAP will make them part of its lab accreditation program. These efforts will help ensure your IHC results give an accurate account of the cancer’s ER/PR status.

"Patients must look for appropriate facilities to [get] testing, ones which see a reasonable volume of patients," Dr. Winer said. "If the test comes back questionable, or if there’s any worry over the quality of the testing, get another test."

Your IHC test results should be reported on the pathology report as "positive" or "negative." Results should spell out the percentage of hormone sensitivity, a rating or some other number that explains how strongly or weakly the cancer cells respond to hormones. Your doctor can help you understand what these numbers mean, answer questions about how the test was conducted and explore the treatment implications.

"It’s up to the doctor and the patient to determine [the] best course of action," Dr. Winer said. "If [they are] unsure of test results, they must weigh the benefits of a drug versus possible side effects and adverse reactions. Taking in consideration the risk of recurrence, consulting with other doctors and the patient, the treating physician should recommend the best course of action for [the] patient."

M.E.H. Hammond, et al. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer. Published online ahead of print in Arch Pathol Lab Med and JCO, April 19, 2010.

Read the full guideline on estrogen- and progesterone-receptor testing in breast cancer.