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

Jørgensen, Charlotte Levin Tykjær LU ; Larsson, Anna Maria LU ; Forsare, Carina LU orcid ; Aaltonen, Kristina LU ; Jansson, Sara LU ; Bradshaw, Rachel ; Bendahl, Pär Ola LU and Rydén, Lisa LU orcid (2021) In Cancers 13(7).
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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Metastatic breast cancer, PAM50 breast cancer intrinsic subtype, Subtype shift, Tumor heterogeneity, Tumor progression
in
Cancers
volume
13
issue
7
article number
1592
publisher
MDPI AG
external identifiers
  • scopus:85103290856
  • pmid:33808271
ISSN
2072-6694
DOI
10.3390/cancers13071592
language
English
LU publication?
yes
id
975718d8-4512-4cf8-b8b6-3eac4c38cca4
date added to LUP
2021-04-07 08:30:02
date last changed
2024-06-16 11:52:58
@article{975718d8-4512-4cf8-b8b6-3eac4c38cca4,
  abstract     = {{<p>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 (P<sub>symmetry</sub> = 0.002), in 31/61 between PTs and DMs (P<sub>symmetry</sub> &lt; 0.001), and in 16/38 between LNMs and DMs (P<sub>symmetry</sub> = 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.</p>}},
  author       = {{Jørgensen, Charlotte Levin Tykjær and Larsson, Anna Maria and Forsare, Carina and Aaltonen, Kristina and Jansson, Sara and Bradshaw, Rachel and Bendahl, Pär Ola and Rydén, Lisa}},
  issn         = {{2072-6694}},
  keywords     = {{Metastatic breast cancer; PAM50 breast cancer intrinsic subtype; Subtype shift; Tumor heterogeneity; Tumor progression}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Pam50 intrinsic subtype profiles in primary and metastatic breast cancer show a significant shift toward more aggressive subtypes with prognostic implications}},
  url          = {{http://dx.doi.org/10.3390/cancers13071592}},
  doi          = {{10.3390/cancers13071592}},
  volume       = {{13}},
  year         = {{2021}},
}