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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
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- Jørgensen, Charlotte Levin Tykjær (författare)
- Lund University,Lunds universitet,The Liquid Biopsy och Tumörprogression i Bröstcancer,Forskargrupper vid Lunds universitet,The Liquid Biopsy and Tumor Progression in Breast Cancer,Lund University Research Groups
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- Larsson, Anna Maria (författare)
- Lund University,Lunds universitet,The Liquid Biopsy och Tumörprogression i Bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,The Liquid Biopsy and Tumor Progression in Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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- Forsare, Carina (författare)
- Lund University,Lunds universitet,Individuell Bröstcancerbehandling,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Personalized Breast Cancer Treatment,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- (creator_code:org_t)
- 2021-03-30
- 2021
- Engelska.
- Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:7
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Metastatic breast cancer
- PAM50 breast cancer intrinsic subtype
- Subtype shift
- Tumor heterogeneity
- Tumor progression
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