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Original article
Comprehensive profiling of metaplastic breast carcinomas reveals frequent overexpression of programmed death-ligand 1
  1. Upasana Joneja1,
  2. Semir Vranic2,3,
  3. Jeffrey Swensen4,
  4. Rebecca Feldman4,
  5. Wangjuh Chen4,
  6. Jeffrey Kimbrough4,
  7. Nianqing Xiao4,
  8. Sandeep Reddy4,
  9. Juan Palazzo1,
  10. Zoran Gatalica4
  1. 1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA
  2. 2Department of Pathology, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
  3. 3School of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  4. 4Caris Life Sciences, Phoenix, Arizona, USA
  1. Correspondence to Dr Upasana Joneja, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University Hospital, 132 S. 10th Street, Main building, Suite 285, Philadelphia, PA 19107, USA; upasana.joneja{at}jefferson.edu

Abstract

Aims Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy than ductal carcinoma. In molecular terms, MBCs usually cluster with triple-negative breast cancers (TNBCs), but have a worse prognosis than TNBCs. Studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches. The aim of the present study was to characterise MBCs on a molecular level and test programmed death-ligand 1 (PD-L1) biomarker expression in MBCs for future therapeutic interventions.

Methods We profiled 297 samples (MBC (n=75), TNBC (n=106), human epidermal growth factor receptor 2 (HER2)-positive breast cancers (n=32) and hormone-positive breast cancers (n=84)) by next-generation sequencing. Immunohistochemistry for PD-L1 and programmed cell death 1 (PD-1) expression was performed using automated procedures.

Results The most commonly mutated genes in MBCs included TP53 (56%) and PIK3CA (23%). Pathogenic mutations in other genes, including HRAS, FBXW7, PTEN, AKT1 and SMAD4, were rare. PD-L1 expression was detected in a significantly higher proportion of MBCs (46%) than in other subtypes (6% each in hormone-positive and HER2-positive breast cancers, and 9% in TNBC, not otherwise specified, p<0.001). PD-1-positive tumour infiltrating lymphocytes (TILs) varied greatly in MBCs.

Conclusions Comprehensive profiling of a large cohort of this rare subtype of breast carcinoma highlighted the predominance of TP53 mutation and increased PD-L1 expression in carcinoma cells. These results can be exploited in clinical trials using immune checkpoint inhibitors.

  • BREAST CANCER
  • BREAST PATHOLOGY
  • TUMOUR BIOLOGY
  • GENETICS

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/jclinpath-2016-203874

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    Footnotes

    • Handling editor Runjan Chetty

    • Funding Caris Life Sciences.

    • Competing interests JS, RF, WC, JK, NX, SR and ZG are employees of Caris Life Sciences. SV has received honoraria from Caris Life Sciences.

    • Ethics approval IRB.

    • Provenance and peer review Not commissioned; externally peer reviewed.