Limited human epidermal growth factor receptor 2 discordance in metastatic breast cancer patients treated with trastuzumab, a population based study.
BACKGROUND
Accurate assessment of the human epidermal growth factor receptor 2 (HER2) in breast cancer is essential for proper treatment decisions. HER2 positivity confirmation rates in breast cancer trials by central testing pathology laboratories were reported to be approximately 85%. The aim of our study was to assess in a population based sample concordance of HER2 status in metastatic breast cancer (MBC) patients locally tested HER2 positive and treated with trastuzumab. Moreover cost-effectiveness of in situ hybridisation (ISH) in patients with an immunohistochemical score 3+ (IHC3+) was explored.


METHODS
MBC patients treated between 2005 and 2009 with trastuzumab-based therapy in North East Netherlands were identified by a survey of hospital pharmacies. Primary tumour samples were retested centrally for HER2 status using 1 immunohistochemical (IHC) method and two methods using ISH on tissue micro-arrays. Potential discordant patients were retested on whole tumour slides. HER2 positivity was defined as: (1) ISH amplification (according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) clinical practice Guideline Update) and (2) when ISH failed an IHC score of 3+. Cost-effectiveness was estimated using potential ISH and treatment costs.


RESULTS
HER2 status could be retested in 174 of 194 (90%) patients. The HER2 concordance rate was 87%. The 21 discordant patients were in the 67% due to primary HER2 testing with only IHC. Overall survival of HER2 discordant and concordant patients was not significantly different (18 versus 25months, p=0.131). Structural ISH in the case of IHC3+ has an estimated potential saving of €87,710 per 100 patients.


CONCLUSIONS
HER2 concordance in a population based study is comparable to those described in selected populations. Discordance is mostly due to testing with only IHC. ISH in the case of IHC3+ is cost-effective.
Department of Internal Medicine, Martini Hospital, Groningen, The Netherlands. Electronic address: j.vanrooijen@mzh.nl.
J M
JM
van Rooijen
Department of Research, Comprehensive Cancer Centre the Netherlands, Utrecht, The Netherlands.
L
L
de Munck
Department of Internal Medicine, Isala Klinieken Zwolle, Zwolle, The Netherlands.
J C
JC
de Graaf
Department of Research, Comprehensive Cancer Centre the Netherlands, Utrecht, The Netherlands; MIRA Institute, Health Technology and Services Research, University of Twente, Enschede, The Netherlands.
S
S
Siesling
Department of Medical Oncology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
E G
EG
de Vries
Department of Pathology, Isala Klinieken Zwolle, Zwolle, The Netherlands.
J E
JE
Boers
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003362:Cost-Benefit Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000191:economics / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000191:economics / Q000379:methods; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009426:Netherlands; D017063:Outcome Assessment, Health Care / Q000379:methods; D011159:Population Surveillance / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
HER2 concordance; HER2 positive breast cancer; HER2 testing; Immunohistochemistry; In situ hybridisation; Trastuzumab