Double-equivocal HER2 invasive breast carcinomas: Institutional experience and review of literature

Context.—HER2 status is a prognostic factor and therapeutic target in invasive breast carcinomas. Reflex testing using an alternate method is recommended on equivocal cases via immunohistochemistry or fluorescence in situ hybridization (FISH). Therapeutic dilemmas arise when both tests are equivocal. The standard chromosome 17 centromere reference probe (CEP17) is in close proximity to the HER2 locus and may be coamplified, leading to equivocal results. Alternate chromosome 17 reference probes may aid in establishing the true HER2 status. Objective.—To describe our institutional experience using D17S122 probe for reflex FISH testing on double-equivocal invasive breast carcinomas and review the literature on alternate reference probes. Data Sources.—Twenty-two patients with double-equivocal invasive breast carcinomas, defined as HER2 immunohistochemistry score 2þ and FISH equivocal per the 2013 guidelines, were reviewed. Reflex FISH was performed with alternate probe D17S122 and the HER2 status classified for 11 cases by using a revised HER2:D17S122 ratio. Seven of 11 cases (63.6%) were ultimately classified as HER2 positive, while 4 cases (36.4%) remained equivocal. The 7 positive cases showed a HER2:D17S122 greater than 2.0. Conclusions.—Alternate probe D17S122 reclassified more than half of our cases as HER2 positive. Alternate probes may establish true HER2 status and direct proper management, as evidenced by our experience and the literature. Additional investigation is needed to determine which alternate probe(s) is(are) best for reflex testing. Finally, the American Society of Clinical Oncology/College of American Pathologists guidelines may need to be updated to reflect more specific recommendations for the utilization of appropriate probes in double-equivocal HER2 cases.