ASCO/CAP issue hormone receptor testing guidelines

The goal is to improve the accuracy of immunohistochemistry test results, a panel member said.

The American Society of Clinical Oncology and the College of American Pathologists cooperatively released a guideline aimed at improving the accuracy of immunohistochemistry testing in patients with breast cancer for their estrogen receptor and progesterone receptor expression status.

ASCO and the College of American Pathologists (CAP) formed an international expert panel that systematically reviewed and evaluated medical research literature in partnership with Cancer Care Ontario to develop recommendations for optimal testing performance. The panel reviewed 337 studies.

Patients with hormone receptor-positive invasive breast cancer treated with endocrine therapies have improved survival. Immunohistochemistry is an established assay to determine the ER/progesterone receptor (PR) status of a tumor. However, about 20% of immunohistochemistry test results may be inaccurate (false-positive or false-negative), according to researchers.

“There is clearly a need to accurately identify breast cancer subtypes as ER and/or PR-positive to help us identify those patients most likely to benefit from endocrine therapy and minimize the risk of potentially denying effective and life-saving therapy to patients incorrectly labeled as having ER/PR-negative invasive disease, while allowing patients with true ER/PR-negative disease to be considered for other therapies,” Antonio C. Wolff, MD, FACP, said in a press release.

Wolff is 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 Baltimore.

The main goal of the ASCO/CAP ER/PR guideline is to improve the accuracy of test results and ensure that patients receive appropriate care, according to Wolff.

Testing recommendations

Based on its review, the panel recommended the following:

Test ER and PR status on all newly diagnosed invasive breast cancers (primary site and/or metastatic site). If appropriate, repeat testing in patients with a known breast cancer diagnosis who present with a local or distant recurrence.
Establish uniform testing measures focused on proven, reliable and reproducible assays and procedures.
Have testing laboratories validate their assays against existing, clinically validated tests. The results should concur at least 90% of the time with that of the clinically validated assays for positive receptor status and at least 95% of the time for negative receptor status.
Transport breast tissue specimens from the OR to the pathology laboratory as soon as they are available for gross assessment. The time from tumor removal to initiation of fixation should be one hour or less. Fixation of the sample in neutral buffered formalin must extend for at least six hours but less than 72 hours.
Perform ER and PR testing in a CAP-accredited laboratory or in a laboratory meeting the accreditation requirements listed in the guideline. Also, the CAP will mandate that every accredited lab performing these tests participate in a proficiency testing program.
Consider an ER and PR test performed by an immunohistochemistry assay as positive if at least 1% of the tumor sample tests positive. The panel recognizes that it is reasonable for oncologists to discuss the pros and cons of endocrine therapy with patients whose tumors contain low levels of ER (1% to 10% weakly positive cells) and to make an informed decision based on available information.

In addition to establishing a guideline, ASCO and CAP have developed clinical tools and resources for oncologists and pathologists that summarize the findings and recommendations. There is a slide presentation on ASCO’s Web site and a guideline summary published in the Journal of Oncology Practice. Additionally, CAP has developed a Breast Predictive Factors Testing Certificate Program and associated continuing medical education courses.

Goal of guideline

“It is our hope that the ASCO/CAP ER/PR guideline will facilitate processes at each health system and institution, so that appropriate measures to ensure accurate predictive biomarker testing (including ER/PR) are in place and that breast cancer patients receive the highest quality care possible,” Elizabeth Hammond, MD, FCAP, said in a press release.

Hammond is co-chair of the ASCO/CAP Hormone Receptor Testing in Breast Cancer Panel and professor of pathology at the University of Utah School of Medicine in Salt Lake City.

“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,” Hammond said.

The ASCO/CAP panel may review new methods and predictive assays to identify patients most likely to benefit from endocrine therapies as new high-level data on validated assays and outcomes become available.

This is a much needed set of recommendations for technical issues, including processing. Prospective evidence for what is to be considered “hormone positive” in terms of specific degree for benefit to anti-estrogens (based on percentage positivity) still needs additional data.

– Edith A. Perez, MD
HemOnc Today Editorial Board member

Hammond MEH. J Clin Oncol. 2009;doi:10.1200/JCO.2009.25.6529.