The epidermal growth factor receptor (EGFR / HER-1) gatekeeper mutation T790M is present in European patients with early breast cancer

PLoS One. 2015 Aug 12;10(8):e0134398. doi: 10.1371/journal.pone.0134398. eCollection 2015.

Abstract

The epidermal growth factor receptor (EGFR) is one of the major oncogenes identified in a variety of human malignancies including breast cancer (BC). EGFR-mutations have been studied in lung cancer for some years and are established as important markers in guiding therapy with tyrosine kinase inhibitors (TKIs). In contrast, EGFR-mutations have been reported to be rare if not absent in human BC, although recent evidence has suggested a significant worldwide variation in somatic EGFR-mutations. Therefore, we investigated the presence of EGFR-mutations in 131 norwegian patients diagnosed with early breast cancer using real-time PCR methods. In the present study we identified three patients with an EGFR-T790M-mutation. The PCR-findings were confirmed by direct Sanger sequencing. Two patients had triple-negative BC (TNBC) while the third was classified as luminal-A subtype. The difference in incidence of T790M mutations comparing the TNBC subgroup with the other BC subgroups was statistical significant (P = 0.023). No other EGFR mutations were identified in the entire cohort. Interestingly, none of the patients had received any previous cancer treatment. To our best knowledge, the EGFR-T790M-TKI-resistance mutation has not been previously detected in breast cancer patients. Our findings contrast with the observations made in lung cancer patients where the EGFR-T790M-mutation is classified as a typical "second mutation"causing resistance to TKI-therapy during ongoing anticancer therapy. In conclusion, we have demonstrated for the first time that the EGFR-T790M-mutation occurs in primary human breast cancer patients. In the present study the EGFR-T790M mutation was not accompanied by any simultaneous EGFR-activating mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / genetics*
  • Europe
  • Female
  • Humans
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology

Substances

  • EGFR protein, human
  • ErbB Receptors

Grants and funding

The present work was supported by scientific grants provided by Bodil and Magne´s Cancer Research Fund, Oslo, Norway and the Akershus University Hospital (internal strategic funding).