The College of American Pathologists (CAP) and the American Society of Clinical Oncology (ASCO) today issued a joint guideline aimed at improving the accuracy of immunohistochemistry (IHC) testing for the expression status of estrogen (ER) and progesterone receptors (PgR) in breast cancer. The two groups conducted a systematic review of medical research literature in partnership with Cancer Care Ontario to develop the recommendations. The guideline is being published in the April 19 issues of ASCO’s Journal of Clinical Oncology (JCO) and CAP’s Archives of Pathology & Laboratory Medicine.

As many as two-thirds of breast cancers are ER and/or PgR-positive with their growth influenced by activation of the estrogen receptor pathway. The purpose of ER/PgR testing is to identify breast cancer patients whose tumors express ER and/or PgR (hormone receptor-positive), and who should therefore be considered candidates for treatment with endocrine therapies, which may include options like tamoxifen, an aromatase inhibitor, and/or suppression of ovarian function, as appropriate. These treatments can substantially improve survival in patients with hormone receptor-positive invasive breast cancer. Immunohistochemistry is an established assay to determine the ER/PgR status of a tumor by measuring protein amounts of ER and PgR in breast cancer cells. However, up to 10-20 percent of IHC test results throughout the world may be inaccurate (false-positive or false-negative).

“There is clearly a need to accurately identify breast cancer subtypes as ER and/or PgR-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/PgR-negative invasive disease, while allowing patients with true ER/PgR-negative disease to be considered for other therapies.” said Antonio C. Wolff, MD, FACP, 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.

The guideline recommends the following:

* Testing ER and PgR status on all newly diagnosed invasive breast cancers (primary site and/or metastatic site), and whenever appropriate, repeat testing in patients with a known breast cancer diagnosis who now present with a local or distant recurrence.
* Establishing uniform testing measures that focus on proven, reliable and reproducible assays and procedures.
* Having testing laboratories validate their assays against existing and clinically validated tests. Results should agree at least 90 percent of the time with those of the clinically validated assays for positive receptor status and at least 95 percent for negative receptor status.
* Transporting breast tissue specimens from the operating room to the pathology laboratory as soon as they are available for gross assessment. The time from tumor removal to initiation of fixation should be kept to one hour or less. Fixation of the sample in neutral buffered formalin must extend for at least six hours and no longer than 72 hours.
* Performing ER and PgR testing in a CAP-accredited laboratory or in a laboratory that meets the accreditation requirements spelled out in the guideline. CAP will require that every accredited lab performing testing participate in a mandatory proficiency testing program.
* Considering an ER and PgR test performed by an IHC assay as positive if at least one percent of the tumor in the sample tests positive, which helps predict whether a patient is likely to benefit with endocrine treatment. The panel recognized that it is reasonable for oncologists to discuss the pros and cons of endocrine therapy with patients whose tumors contain low levels of ER by IHC (one percent to ten percent weakly positive cells) and to make an informed decision based on available information.

“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 Dr. Wolff.

According to Elizabeth Hammond, MD, FCAP, co-chair of the ASCO/CAP Hormone Receptor Testing in Breast Cancer Panel, pathologist at Intermountain Healthcare, and professor of pathology at the University of Utah School of Medicine, “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.”

Classifying subtypes of breast cancer by a tumor’s biological characteristics (tumor phenotype) can include whether or not it is hormone (estrogen or progesterone) receptor positive, human epidermal growth factor receptor 2 (HER2) positive, or “triple negative,” lacking receptors for estrogen, progesterone, and HER2. The latter, HER2, plays a role in cancer cell growth and spread and identifies patients that may be considered candidates for treatment with anti-HER2 drugs in the adjuvant or metastatic settings. In 2007, ASCO and CAP issued clinical practice guideline recommendations to improve HER2 testing accuracy.

About 20 percent of all women with invasive breast cancer are HER2-positive, meaning they overexpress HER2, and about 15 percent of breast cancers do not express HER2, ER, or PgR receptors (triple-negative). Accurate determination of tumor phenotype is critical to properly select therapy options and individualize treatments.

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. In the future, 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.

The ASCO/CAP Panel also expects that the new ER/PgR guideline will foster improved communications among cancer specialists and also between patients and their doctors. Because of the availability of effective therapies for patients with hormone-receptor positive disease, the panel chairs encourage women who are told to have an ER/PgR-negative breast cancer to discuss the test result with their cancer specialists, including their oncologist and pathologist. 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.

“All medical professionals involved in cancer care want to do the right thing and offer the most correct and appropriate care to their patients. It is our hope that the ASCO/CAP ER/PgR guideline will facilitate processes at each health system and institution, so that appropriate measures to ensure accurate predictive biomarker testing (including ER/PgR) are in place and that breast cancer patients receive the highest quality care possible,” said Dr. Hammond.

In conjunction with the publishing of the guideline, ASCO and CAP have developed clinical tools and resources for oncologists and pathologists that summarize the findings and recommendations. These 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 (CME), which will also allow pathologists to gain special expertise in the development and implementation of these tests.

The clinical practice guideline and other resources are available at http://www.asco.org/guidelines/erpr and http://www.cap.org/center. ASCO also has developed a corresponding patient guide available on ASCO’s patient web site, http://www.cancer.net.

About ASCO
The American Society of Clinical Oncology (ASCO) is the world’s leading professional organization representing physicians who care for people with cancer. With more than 28,000 members, ASCO is committed to improving cancer care through scientific meetings, educational programs and peer-reviewed journals. For ASCO information and resources, visit http://www.asco.org/presscenter.

About the CAP
The College of American Pathologists (CAP) is a medical society that serves more than 17,000 physician members and the laboratory community throughout the world. It is the world’s largest association composed exclusively of board-certified pathologists and is widely recognized as the leader in laboratory quality assurance. The CAP is an advocate for high-quality and cost-effective patient care.

Source:  College of American Pathologists (CAP)