What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC)

Ann Oncol. 2016 May;27(5):920-6. doi: 10.1093/annonc/mdw042. Epub 2016 Feb 15.


Background: Mammary analogue secretory carcinoma (MASC) is a recently described pathologic entity. We report the case of a patient with an initial diagnosis of salivary acinic cell carcinoma later reclassified as MASC after next-generation sequencing revealed an ETV6-NTRK3 fusion.

Patients and methods: This alteration was targeted with the pan-Trk inhibitor entrectinib (Ignyta), which possesses potent in vitro activity against cell lines containing various NTRK1/2/3 fusions.

Results: A dramatic and durable response was achieved with entrectinib in this patient, followed by acquired resistance that correlated with the appearance of a novel NTRK3 G623R mutation. Structural modeling predicts that this alteration sterically interferes with drug binding, correlating to decreased sensitivity to drug inhibition observed in cell-based assays.

Conclusions: This first report of clinical activity with TrkC inhibition and the development of acquired resistance in an NTRK3-rearranged cancer emphasize the utility of comprehensive molecular profiling and targeted therapy for rare malignancies (NCT02097810).

Keywords: ETV6-NTRK3; TrkC; entrectinib; mammary analogue secretory carcinoma.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Benzamides / administration & dosage*
  • Benzamides / adverse effects
  • Biomarkers, Tumor / genetics
  • Carcinoma, Acinar Cell / diagnosis*
  • Carcinoma, Acinar Cell / drug therapy
  • Carcinoma, Acinar Cell / genetics
  • Carcinoma, Acinar Cell / pathology
  • Clinical Trials as Topic
  • Crizotinib
  • Diagnosis, Differential
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Indazoles / administration & dosage*
  • Indazoles / adverse effects
  • Mammary Analogue Secretory Carcinoma / diagnosis*
  • Mammary Analogue Secretory Carcinoma / drug therapy
  • Mammary Analogue Secretory Carcinoma / genetics
  • Mammary Analogue Secretory Carcinoma / pathology
  • Mutation
  • Oncogene Proteins, Fusion / genetics*
  • Pyrazoles / administration & dosage
  • Pyridines / administration & dosage
  • Salivary Gland Neoplasms / diagnosis*
  • Salivary Gland Neoplasms / drug therapy
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / pathology


  • Benzamides
  • Biomarkers, Tumor
  • ETV6-NTRK3 fusion protein, human
  • Indazoles
  • Oncogene Proteins, Fusion
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • entrectinib

Associated data

  • ClinicalTrials.gov/NCT02097810