NEW YORK (Reuters Health) – Up to 20% of tests for estrogen and progesterone receptors in breast cancers are false negatives or false positives, according to a consensus panel.

The panel, convened by the American Society of Clinical Oncology and the College of American Pathologists, in partnership with Cancer Care Ontario, developed new guidelines for testing and interpretation of immunohistochemical assays for these hormone receptors.

The new recommendations were published jointly online April 19 in the Journal of Clinical Oncology and the Archives of Pathology & Laboratory Medicine.

“Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria,” according to first author Dr. M. Elizabeth H. Hammond, from the University of Utah School of Medicine in Salt Lake City and colleagues.

ASCO and CAP commissioned a systematic review and evaluation of the literature on hormone receptor testing published since 1990. That review has not yet been published, but its findings “served as the primary source of evidence” for the new guidelines, the authors said.

“There is no gold standard assay available” for hormone status testing of breast cancer tumors, the researchers found. The best option is to use a “clinically validated” test, i.e., an assay “whose results had been validated against clinical benefit from endocrine therapy.” The authors cite methods described by Harvey et al in 1999 and by Mohsin et al in 2004, as well as an assay manufactured by Dako (Glostrup, Denmark).

Among the panel’s other recommendations: a call to determine estrogen receptor (ER) and progesterone receptor (PgR) status on all invasive breast cancers and breast cancer recurrences. The panel also proposes a testing algorithm that “relies on accurate, reproducible assay performance” and specifies elements to “reliably reduce assay variation.”

Also, they say, ER and PgR assays should be considered positive if the sample contains “at least 1% positive tumor nuclei…in the presence of expected reactivity of internal (normal epithelial elements) and external controls.”

At a minimum, the panel said, reports of immunohistochemical assays for ER and PgR should include the following:
–Percentage/proportion of tumor cells staining positively,
–Intensity of staining (mild, moderate or strong), and
–An interpretation of the assay as either receptor negative, receptor positive, or receptor uninterpretable.

The complete ASCO/CAP recommendations on immunohistochemical testing of estrogen and progesterone receptors in breast cancer can be found here:


J Clin Oncol 2010.