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CAP/ASCO Issues New Guidelines to Improve IHC-based ER/PgR Analysis in Breast Cancer

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Originally published April 20.

The College of American Pathologists and the American Society of Clinical Oncology issued joint guidelines this week for immunohistochemistry testing for the expression status of estrogen and progesterone receptors in breast cancer.

The recommendations were developed following a systematic review of medical literature in collaboration with Cancer Care Ontario. The guidelines were published in the April 19 issues of ASCO's Journal of Clinical Oncology and CAP's Archives of Pathology & Laboratory Medicine.

IHC is commonly used to measure the amount of ER and PgR proteins in breast cancer cells, which can help guide treatment with endocrine therapies, such as tamoxifen, that have shown to improve survival.

However, between 10 percent and 20 percent of IHC test results throughout the world may be inaccurate, yielding false-positive or false-negative results, according to a CAP/ASCO joint statement announcing the published guidelines.

“The main goal of the ASCO/CAP ER/PgR guideline is to improve the accuracy of test results and ensure that patients receive appropriate care like endocrine therapy, as it has the potential to improve survival and save lives. Widespread access to accurate ER/PgR testing is also critical because breast cancer is the most common cause of cancer death in women in low and middle-income countries, and most of them have ER and/or PgR-positive disease,” said Antonio Wolff, MD, co-chair of the ASCO/CAP Hormone Receptor Testing in Breast Cancer Panel and associate professor of oncology at the Johns Hopkins Kimmel Comprehensive Cancer Center.

In order to mitigate such inaccuracies in IHC testing, the new CAP/ASCO guidelines recommend:

• Testing ER and PgR status on all newly diagnosed invasive breast cancer patients, and repeat testing on those whose breast cancer recurred.
• Establishing uniform testing measures using "proven, reliable and reproducible assays and procedures."
• Validating laboratory-based assays against existing and clinically validated tests, so that results agree at least 90 percent of the time for positive receptor status and at least 95 percent for negative receptor status.
• Maintaining the time-from-tumor removal to initiation-of-fixation to one hour or less and fixating the sample in neutral buffered formalin for at least six hours but not longer than 72 hours.
• Performing ER and PgR testing in a lab that is CAP-accredited or at least meets the accreditation requirements spelled out in the guideline, including mandatory participation in a proficiency testing program.
• Considering an IHC-based ER and PgR test result as positive if at least 1 percent of the tumor in the sample tests positive, "which helps predict whether a patient is likely to benefit with endocrine treatment," and allows "oncologists to discuss the pros and cons of endocrine therapy with patients whose tumors contain low levels of ER by IHC."

“Increased attention to simple measures such as the handling of tissue specimens from the moment they are taken from the patient to when they reach the pathologist, the uniform fixation of specimens, the standardization and validation of lab assays, rigorous reporting procedures, and greater access to treatment interventions have the potential to significantly improve breast cancer outcomes around the world," Elizabeth Hammond, co-chair of the ASCO/CAP Hormone Receptor Testing in Breast Cancer Panel, said in a statement.

ASCO and CAP are hoping that these new guidelines will help improve conversations between doctors and patients. The guidelines recommend that women with hormone-receptor positive breast cancer who have been told by their oncologist to have a ER/PgR test discuss the results with their doctors.

"This conversation would touch on questions like whether the hormone receptor test result is consistent with the overall pathology assessment of the tumor and whether the ER/PgR testing was done in a manner that is consistent with the new ASCO/CAP guideline," the groups said in a statement.

These new guidelines to improve IHC testing accuracy follow CAP/ASCO's guidelines in 2007 to improve HER2 testing accuracy. In those recommendations, the groups estimated that "as many as 15 percent to 20 percent of the HER2 assays performed in the field may be incorrect when the same specimen was reevaluated in a high-volume, central laboratory" (PGx Reporter 02-28-07).

"The ASCO/CAP Panel chose to specifically focus on IHC assays for ER/PgR testing based on its widespread use, worldwide impact, and large body of evidence available," the groups said. Future joint guidelines may focus on new diagnostic methods and predictive assays to identify patients most likely to benefit from endocrine therapies as data on new technologies and outcomes become available.

These guidelines on IHC testing have been developed alongside clinical tools and resources that summarize the recommendations for oncologists and pathologists. The resources include a slide presentation on ASCO’s website and a guideline summary in the Journal of Oncology Practice. In addition, CAP has developed a Breast Predictive Factors Testing Certificate Program and associated Continuing Medical Education course, which will allow pathologists to gain special expertise in the development and implementation of these tests.

Additionally, ASCO has added a patient guide to its www.cancer.net patient website.

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