The epidermal growth factor receptor (EGFR / HER-1) gatekeeper mutation T790M is present in European patients with early breast cancer.
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.
Department of Gene Technology, Akershus University Hospital, Lørenskog, Norway; University of Oslo, Institute of Clinical Medicine, Campus at Akershus University Hospital, Lørenskog, Norway.
Vahid
V
Bemanian
University of Oslo, Institute of Clinical Medicine, Campus at Akershus University Hospital, Lørenskog, Norway; Department of Pathology, Akershus University Hospital, Lørenskog, Norway.
Torill
T
Sauer
Department of Breast- and Endocrine Surgery, Akershus University Hospital, Lørenskog, Norway.
Joel
J
Touma
Department of Gene Technology, Akershus University Hospital, Lørenskog, Norway; University of Oslo, Institute of Clinical Medicine, Campus at Akershus University Hospital, Lørenskog, Norway.
Bjørn Arne
BA
Lindstedt
Department of Pathology, Akershus University Hospital, Lørenskog, Norway.
Ying
Y
Chen
Department of Oncology, Akershus University Hospital, Lørenskog, Norway.
Hilde Presterud
HP
Ødegård
Department of Breast- and Endocrine Surgery, Akershus University Hospital, Lørenskog, Norway.
Katja Marjaana
KM
Vetvik
University of Oslo, Institute of Clinical Medicine, Campus at Akershus University Hospital, Lørenskog, Norway; Department of Breast- and Endocrine Surgery, Akershus University Hospital, Lørenskog, Norway.
Ida Rashida
IR
Bukholm
University of Oslo, Institute of Clinical Medicine, Campus at Akershus University Hospital, Lørenskog, Norway; Department of Oncology, Akershus University Hospital, Lørenskog, Norway.
Jürgen
J
Geisler
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005060:Europe; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
C512478:EGFR protein, human; D066246:ErbB Receptors