Pam50 intrinsic subtype profiles in primary and metastatic breast cancer show a significant shift toward more aggressive subtypes with prognostic implications
(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.
(Less)
- author
- Jørgensen, Charlotte Levin Tykjær LU ; Larsson, Anna Maria LU ; Forsare, Carina LU ; Aaltonen, Kristina LU ; Jansson, Sara LU ; Bradshaw, Rachel ; Bendahl, Pär Ola LU and Rydén, Lisa LU
- organization
- publishing date
- 2021
- 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
-
- pmid:33808271
- scopus:85103290856
- 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
- 2024-09-07 17:24:57
@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> < 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}}, }