American Society of Clinical Oncology/College ofAmerican Pathologists guideline recommendations forimmunohistochemical testing of estrogen andprogesterone receptors in breast cancer

Purpose: To develop a guideline to improve theaccuracy of immunohistochemical (IHC) estrogen receptor(ER) and progesterone receptor (PgR) testing in breastcancer and the utility of these receptors as predictivemarkers.Methods: The American Society of Clinical Oncologyand the College of American Pathologists convened aninternational Expert Panel that conducted a systematicreview and evaluation of the literature in partnership withCancer Care Ontario and developed recommendations foroptimal IHC ER/PgR testing performance.Results: Up to 20% of current IHC determinations ofER and PgR testing worldwide may be inaccurate (falsenegative or false positive). Most of the issues with testinghave occurred because of variation in preanalyticvariables, thresholds for positivity, and interpretationcriteria.Recommendations: The Panel recommends that ER andPgR status be determined on all invasive breast cancers andbreast cancer recurrences. A testing algorithm that relieson accurate, reproducible assay performance is proposed.Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be consideredpositive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.(Arch Pathol Lab Med. 2010;134:907–922