Consistency and inconsistency in testing biomarkers in breast cancer. A GRELL study in cut-off variability in the Romance language countries

Emanuele Crocetti, Adele Caldarella, Stefano Ferretti, Eva Ardanaz, Patrick Arveux, Simona Bara, Enrique Barrios, Maria J. Bento, Andrea Bordoni, Carlotta Buzzoni, Giuseppina Candela, Françoise Colombani, Patricia Delafosse, Massimo Federico, Julie Francart, Adriano Giacomin, Pascale Grosclaude, Anne V. Guizard, Isabel Izarzugaza, Isabelle KonzelmannFrancesco La Rosa, Benedicte Lapotre, Nathalie Leone, Karine Ligier, Lucia Mangone, R. Marcos-Gragera, Ruth Martinez, Maria J. Michelena, Maria Michiara, Ana Miranda, Florence Molinié, Conception Mugarza-Gomez, Eugenio Paci, Silvano Piffer, Montserrat Puig-Vives, Claudio Sacchettini, Maria J. Sánchez, Adele Traina, Brigitte Tretarre, Rosario Tumino, Elke Van Vaerenbergh, Michel Velten, Anne S. Woronoff

Research output: Contribution to journalArticle


Purpose: Biological markers are crucial factors in order to differentiate female breast cancers and to determine the right therapy. This study aims at evaluating whether testing for biomarkers for female breast cancer has similar frequency and characteristics across and within countries. Methods: Population-based cancer registries of the Association for cancer registration and epidemiology in Romance language countries (GRELL) were asked to complete a questionnaire on biomarkers testing. The data collected referred to invasive female breast cancer cases diagnosed between 2004 and 2009. The investigation focused on 1) the overexpression and amplification of the human epidermal growth factor receptor 2 oncogene (HER2); 2) the expression of oestrogen (ER) and progesterone (PgR) receptors; and 3) the proliferation index (PI). Weighted percentages, the heterogeneity among and within countries, and the correlation between responses and calendar years were evaluated. The study was based on 19,644 breast cancers. Results: Overall, 85.9% of the cases were tested for HER2, 91.8% for both ER and PgR, and 74.1% for proliferative markers. For HER2 and ER-PgR, the frequency of testing increased from 2004 to 2009. Testing varied among countries (HER2 from 82.0% to 95.9%, ER-PgR from 89.3% to 98.9%, PI from 10% to 92%) and also within the same country (e.g. HER2 in Italy from 51% to 99%) as well as within single cancer registries. The most relevant differences were in the scores for positive/negative/not clearly defined HER2 (e.g. HER2 was defined positive if IHC 3+ in 21/33 registries), and in the cut-off of positive cells for ER/PgR (from >0% to >30%) and PI positivity (from >0% to >20%). Conclusions: Biological markers are widely tested in the Romance language countries; however, the parameters defining their positivity may vary, raising concerns about homogeneity in breast cancer classification and treatment.

Original languageEnglish
Pages (from-to)476-481
Number of pages6
Issue number4
Publication statusPublished - Aug 2013



  • Biomarkers
  • Breast cancer
  • HER2
  • Oestrogen receptor
  • Progesterone receptor
  • Proliferation index

ASJC Scopus subject areas

  • Surgery

Cite this

Crocetti, E., Caldarella, A., Ferretti, S., Ardanaz, E., Arveux, P., Bara, S., Barrios, E., Bento, M. J., Bordoni, A., Buzzoni, C., Candela, G., Colombani, F., Delafosse, P., Federico, M., Francart, J., Giacomin, A., Grosclaude, P., Guizard, A. V., Izarzugaza, I., ... Woronoff, A. S. (2013). Consistency and inconsistency in testing biomarkers in breast cancer. A GRELL study in cut-off variability in the Romance language countries. Breast, 22(4), 476-481.