The incidence of false-negative immunohistochemistry (IHC) is only 1% in patients with primary breast cancer, according to a prospective multicenter Canadian study presented at the meeting. This is good news in relation to standardized testing utilizing IHC and in situ hybridization techniques for the accurate diagnosis of patients expressing HER2.
Overexpression and amplification of HER2 is present in 15% to 20% of all patients with breast cancer and is associated with a higher-grade cancer and an increased risk of tumor recurrence, according to Wedad Hanna, MBBCh, MD, Professor of Anatomic Pathology, Department of Laboratory Medicine and Pathobiology, and Affiliate Scientist, Odette Cancer Research Program, Sunnybrook Research Institute, University of Toronto, Ontario.
HER2-positive status is predictive of response not only to trastuzumab (Herceptin) but also to newer agents, such as pertuzumab (Perjeta) and trastuzumab emtansine (T-DM1). Trastuzumab is also beneficial in the management of ductal carcinoma in situ (DCIS).
One of the challenges in testing for HER2 is that tissue from one area of the breast may test positive for HER2 while tissue from a different site may test negative, Dr Hanna noted.
Investigators in this study evaluated breast resection specimens obtained in 2010 and 2011, focusing on resection specimens that were scored 0 or 1+ via IHC. A score of 0 to 1+ is considered to be HER2-negative.
The final analysis included 711 cases, including 162 patients with grade 1 tumors, 320 with grade 2 tumors, and 225 patients with grade 3 tumors (4 patients were not assigned a grade). Only 7 of the 711 patients (0.98%) undergoing IHC and in situ hybridization had a false-negative result, Dr Hanna reported.
The results of this study confirmed previously published Canadian guidelines recommending initial IHC testing of all invasive carcinomas followed by in situ hybridization on equivocal cases.
Ironically, Dr Hanna served as a cochairperson for the committee that developed the Canadian guidelines. She suggested that HER2 testing should be considered in all patients with DCIS, and that HER2-positive patients should receive more aggressive treatment than those with HER2-negative disease.
Dr Hanna further emphasized the validity of these results, noting that study cohorts were represented by patients who did not receive any additional treatment beyond surgery and, therefore, exemplify the natural course of the disease. In addition, she maintained that the testing was robust in that all tumors were tested with IHC and in situ hybridization.
