Human epidermal growth factor receptor 2 testing in primary breast cancer in the era of standardized testing: a Canadian prospective study.
OBJECTIVE
Therapies that target overexpression of human epidermal growth factor receptor 2 (HER2) rely on accurate and timely assessment of all patients with new diagnoses. This study examines HER2 testing of primary breast cancer tissue when performed with immunohistochemistry (IHC) and additional in situ hybridization (ISH) for negative cases (IHC 0/1+). The analysis focuses on the rate of false-negative HER2 tests, defined as IHC 0/1+ with an ISH ratio ≥ 2.0, in eight pathology centers across Canada.


METHODS
Whole sections of surgical resections or tissue microarrays (TMAs) from invasive breast carcinoma tissue were tested by both IHC and ISH using standardized local methods. Samples were scored by the local breast pathologist, and consecutive HER2-negative IHC results (IHC 0/1+) were compared with the corresponding fluorescence or silver ISH result.


RESULTS
Overall, 711 surgical excisions of primary breast cancer were analyzed by IHC and ISH; HER2 and chromosome 17 centromere (CEP17) counts were available in all cases. The overall rate of false-negative samples was 0.84% (six of 711 samples). Interpretable IHC and ISH scores were available in 1,212 cases from TMAs, and the overall rate of false-negative cases was 1.6% (16 of 978 cases).


CONCLUSIONS
Our observation confirms that IHC is an adequate test to predict negative HER2 status in primary breast cancer in surgical excision specimens, even when different antibodies and IHC platforms are used. The study supports the American Society of Clinical Oncology/College of American Pathologists and Canadian testing algorithms of using IHC followed by ISH for equivocal cases.
Wedad M. Hanna and Sharon Nofech-Mozes, Sunnybrook Health Sciences Centre, University of Toronto; Wedad M. Hanna, Martin C. Chang, and Sharon Nofech-Mozes, University of Toronto; Martin C. Chang, Mount Sinai Hospital, Toronto; Susan J. Robertson, Ottawa General Hospital and University of Ottawa, Ottawa; Sandip K. SenGupta, Kingston General Hospital and Queen's University, Kingston, Ontario; Penny J. Barnes, Capital Health District Authority and Dalhousie University, Halifax, Nova Scotia; C. Blake Gilks, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia; Henrike Rees and Louise Quenneville, Saskatoon City Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and Anthony M. Magliocco, Esoteric Laboratory Services, Moffitt Cancer Center, Tampa, FL. wedad.hanna@sunnybrook.ca.
Wedad M
WM
Hanna
Wedad M. Hanna and Sharon Nofech-Mozes, Sunnybrook Health Sciences Centre, University of Toronto; Wedad M. Hanna, Martin C. Chang, and Sharon Nofech-Mozes, University of Toronto; Martin C. Chang, Mount Sinai Hospital, Toronto; Susan J. Robertson, Ottawa General Hospital and University of Ottawa, Ottawa; Sandip K. SenGupta, Kingston General Hospital and Queen's University, Kingston, Ontario; Penny J. Barnes, Capital Health District Authority and Dalhousie University, Halifax, Nova Scotia; C. Blake Gilks, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia; Henrike Rees and Louise Quenneville, Saskatoon City Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and Anthony M. Magliocco, Esoteric Laboratory Services, Moffitt Cancer Center, Tampa, FL.
Penny J
PJ
Barnes
Wedad M. Hanna and Sharon Nofech-Mozes, Sunnybrook Health Sciences Centre, University of Toronto; Wedad M. Hanna, Martin C. Chang, and Sharon Nofech-Mozes, University of Toronto; Martin C. Chang, Mount Sinai Hospital, Toronto; Susan J. Robertson, Ottawa General Hospital and University of Ottawa, Ottawa; Sandip K. SenGupta, Kingston General Hospital and Queen's University, Kingston, Ontario; Penny J. Barnes, Capital Health District Authority and Dalhousie University, Halifax, Nova Scotia; C. Blake Gilks, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia; Henrike Rees and Louise Quenneville, Saskatoon City Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and Anthony M. Magliocco, Esoteric Laboratory Services, Moffitt Cancer Center, Tampa, FL.
Martin C
MC
Chang
Wedad M. Hanna and Sharon Nofech-Mozes, Sunnybrook Health Sciences Centre, University of Toronto; Wedad M. Hanna, Martin C. Chang, and Sharon Nofech-Mozes, University of Toronto; Martin C. Chang, Mount Sinai Hospital, Toronto; Susan J. Robertson, Ottawa General Hospital and University of Ottawa, Ottawa; Sandip K. SenGupta, Kingston General Hospital and Queen's University, Kingston, Ontario; Penny J. Barnes, Capital Health District Authority and Dalhousie University, Halifax, Nova Scotia; C. Blake Gilks, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia; Henrike Rees and Louise Quenneville, Saskatoon City Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and Anthony M. Magliocco, Esoteric Laboratory Services, Moffitt Cancer Center, Tampa, FL.
C Blake
CB
Gilks
Wedad M. Hanna and Sharon Nofech-Mozes, Sunnybrook Health Sciences Centre, University of Toronto; Wedad M. Hanna, Martin C. Chang, and Sharon Nofech-Mozes, University of Toronto; Martin C. Chang, Mount Sinai Hospital, Toronto; Susan J. Robertson, Ottawa General Hospital and University of Ottawa, Ottawa; Sandip K. SenGupta, Kingston General Hospital and Queen's University, Kingston, Ontario; Penny J. Barnes, Capital Health District Authority and Dalhousie University, Halifax, Nova Scotia; C. Blake Gilks, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia; Henrike Rees and Louise Quenneville, Saskatoon City Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and Anthony M. Magliocco, Esoteric Laboratory Services, Moffitt Cancer Center, Tampa, FL.
Anthony M
AM
Magliocco
Wedad M. Hanna and Sharon Nofech-Mozes, Sunnybrook Health Sciences Centre, University of Toronto; Wedad M. Hanna, Martin C. Chang, and Sharon Nofech-Mozes, University of Toronto; Martin C. Chang, Mount Sinai Hospital, Toronto; Susan J. Robertson, Ottawa General Hospital and University of Ottawa, Ottawa; Sandip K. SenGupta, Kingston General Hospital and Queen's University, Kingston, Ontario; Penny J. Barnes, Capital Health District Authority and Dalhousie University, Halifax, Nova Scotia; C. Blake Gilks, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia; Henrike Rees and Louise Quenneville, Saskatoon City Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and Anthony M. Magliocco, Esoteric Laboratory Services, Moffitt Cancer Center, Tampa, FL.
Henrike
H
Rees
Wedad M. Hanna and Sharon Nofech-Mozes, Sunnybrook Health Sciences Centre, University of Toronto; Wedad M. Hanna, Martin C. Chang, and Sharon Nofech-Mozes, University of Toronto; Martin C. Chang, Mount Sinai Hospital, Toronto; Susan J. Robertson, Ottawa General Hospital and University of Ottawa, Ottawa; Sandip K. SenGupta, Kingston General Hospital and Queen's University, Kingston, Ontario; Penny J. Barnes, Capital Health District Authority and Dalhousie University, Halifax, Nova Scotia; C. Blake Gilks, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia; Henrike Rees and Louise Quenneville, Saskatoon City Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and Anthony M. Magliocco, Esoteric Laboratory Services, Moffitt Cancer Center, Tampa, FL.
Louise
L
Quenneville
Wedad M. Hanna and Sharon Nofech-Mozes, Sunnybrook Health Sciences Centre, University of Toronto; Wedad M. Hanna, Martin C. Chang, and Sharon Nofech-Mozes, University of Toronto; Martin C. Chang, Mount Sinai Hospital, Toronto; Susan J. Robertson, Ottawa General Hospital and University of Ottawa, Ottawa; Sandip K. SenGupta, Kingston General Hospital and Queen's University, Kingston, Ontario; Penny J. Barnes, Capital Health District Authority and Dalhousie University, Halifax, Nova Scotia; C. Blake Gilks, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia; Henrike Rees and Louise Quenneville, Saskatoon City Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and Anthony M. Magliocco, Esoteric Laboratory Services, Moffitt Cancer Center, Tampa, FL.
Susan J
SJ
Robertson
Wedad M. Hanna and Sharon Nofech-Mozes, Sunnybrook Health Sciences Centre, University of Toronto; Wedad M. Hanna, Martin C. Chang, and Sharon Nofech-Mozes, University of Toronto; Martin C. Chang, Mount Sinai Hospital, Toronto; Susan J. Robertson, Ottawa General Hospital and University of Ottawa, Ottawa; Sandip K. SenGupta, Kingston General Hospital and Queen's University, Kingston, Ontario; Penny J. Barnes, Capital Health District Authority and Dalhousie University, Halifax, Nova Scotia; C. Blake Gilks, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia; Henrike Rees and Louise Quenneville, Saskatoon City Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and Anthony M. Magliocco, Esoteric Laboratory Services, Moffitt Cancer Center, Tampa, FL.
Sandip K
SK
SenGupta
Wedad M. Hanna and Sharon Nofech-Mozes, Sunnybrook Health Sciences Centre, University of Toronto; Wedad M. Hanna, Martin C. Chang, and Sharon Nofech-Mozes, University of Toronto; Martin C. Chang, Mount Sinai Hospital, Toronto; Susan J. Robertson, Ottawa General Hospital and University of Ottawa, Ottawa; Sandip K. SenGupta, Kingston General Hospital and Queen's University, Kingston, Ontario; Penny J. Barnes, Capital Health District Authority and Dalhousie University, Halifax, Nova Scotia; C. Blake Gilks, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia; Henrike Rees and Louise Quenneville, Saskatoon City Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and Anthony M. Magliocco, Esoteric Laboratory Services, Moffitt Cancer Center, Tampa, FL.
Sharon
S
Nofech-Mozes
D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000601:surgery; D002170:Canada; D002886:Chromosomes, Human, Pair 17 / Q000648:ultrastructure; D005188:False Negative Reactions; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human