New Guideline Will Improve Hormone Receptor Testing for Patients with Breast Cancer

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.