Pam50 intrinsic subtype profiles in primary and metastatic breast cancer show a significant shift toward more aggressive subtypes with prognostic implications

Charlotte Levin Tykjær Jørgensen, Anna Maria Larsson, Carina Forsare, Kristina Aaltonen, Sara Jansson, Rachel Bradshaw, Pär Ola Bendahl, Lisa Rydén

Research output: Contribution to journalArticlepeer-review

4 Citations (SciVal)

Abstract

Background: PAM50 breast cancer intrinsic subtyping adds prognostic information in early breast cancer; however, the role in metastatic disease is unclear. We aimed to identify PAM50 subtypes in primary tumors (PTs) and metastases to outline subtype changes and their prognostic role. Methods: RNA was isolated from PTs, lymph node metastases (LNMs), and distant metastases (DMs) in metastatic breast cancer patients (n = 140) included in a prospective study (NCT01322893). Gene expression analyses were performed using the Breast Cancer 360 (BC360) assay from Nano-String. The subtype shifts were evaluated using McNemar and symmetry tests, and clinical outcomes were evaluated with log-rank tests and Cox regression. Results: The PAM50 subtype changed in 25/59 of paired samples between PTs and LNMs (Psymmetry = 0.002), in 31/61 between PTs and DMs (Psymmetry < 0.001), and in 16/38 between LNMs and DMs (Psymmetry = 0.004). Shifts toward subtypes with worse outcomes were the most common. Patients with shifts from the luminal PT to non-luminal DM subtypes had worse progression-free survival compared to patients with a stable subtype (hazard ratio (HR): 2.3; 95% confidence interval (CI): 1.14–4.68, p = 0.02). Conclusion: Strong evidence of PAM50 subtype shifts toward unfavorable subtypes were seen between PTs and metastatic samples. For patients with a shift in subtype from luminal PT to non-luminal DM, a worse prognosis was noted.

Original languageEnglish
Article number1592
JournalCancers
Volume13
Issue number7
DOIs
Publication statusPublished - 2021

Subject classification (UKÄ)

  • Cancer and Oncology

Keywords

  • Metastatic breast cancer
  • PAM50 breast cancer intrinsic subtype
  • Subtype shift
  • Tumor heterogeneity
  • Tumor progression

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