Molecular subtyping improves breast cancer diagnosis in the Copenhagen Breast Cancer Genomics Study
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Molecular subtyping improves breast cancer diagnosis in the Copenhagen Breast Cancer Genomics Study. / Berg, Tobias; Jensen, Maj Britt; Celik, Alan; Talman, Maj Lis; Misiakou, Maria Anna; Knoop, Ann Søegaard; Nielsen, Finn Cilius; Ejlertsen, Bent; Rossing, Maria.
I: JCI insight, Bind 9, Nr. 7, e178114, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Molecular subtyping improves breast cancer diagnosis in the Copenhagen Breast Cancer Genomics Study
AU - Berg, Tobias
AU - Jensen, Maj Britt
AU - Celik, Alan
AU - Talman, Maj Lis
AU - Misiakou, Maria Anna
AU - Knoop, Ann Søegaard
AU - Nielsen, Finn Cilius
AU - Ejlertsen, Bent
AU - Rossing, Maria
N1 - Publisher Copyright: Copyright: © 2024, Berg et al.
PY - 2024
Y1 - 2024
N2 - BACKGROUND. Intrinsic molecular subtypes define distinct biological breast cancers and can be used to further improve diagnosis and risk allocation. METHODS. The Copenhagen Breast Cancer Genomics Study (CBCGS) prospectively included women diagnosed with breast cancer at Rigshospitalet from 2014 to 2021. Eligible patients were females with a primary invasive breast cancer (T1c, if N0M0; otherwise, any T, any N, or any M stage) and no prior malignancy. All patients underwent molecular profiling with the CIT256 and PAM50 molecular profile. RESULTS. In the study period, 2,816 patients were included in the CBCGS. Molecular subtyping showed an increase in nonluminal (molecular-apocrine, luminal C, and Basal-like) as compared with luminal (luminal A, luminal B, and Normal-like) subtypes with increasing stage from I to IV. Across all stages, we found a significant difference in survival among subtypes; 91% of patients with LumA were alive at 5 years compared with 91% for LumB, 84% for LumC, 82% for mApo, and 80% for Basal-like. We identified 442 tumors (16%) that were discordant in subtype between CIT256 and IHC. Discordant subtype proved to be a risk factor of death among patients with IHC luminal breast cancer (hazard ratio [HR], 2.08; 95% CI, 1.51–2.86) in a multivariable Cox regression analysis. Discordance occurred more often among patients with N3, stage IV, or grade III disease. CONCLUSION. Our findings indicate that molecular subtypes are a predominant classification for survival. Assessment is particularly crucial for patients with IHC luminal breast cancer with known high-risk factors, since they are at an increased risk of harboring an aggressive molecular subtype.
AB - BACKGROUND. Intrinsic molecular subtypes define distinct biological breast cancers and can be used to further improve diagnosis and risk allocation. METHODS. The Copenhagen Breast Cancer Genomics Study (CBCGS) prospectively included women diagnosed with breast cancer at Rigshospitalet from 2014 to 2021. Eligible patients were females with a primary invasive breast cancer (T1c, if N0M0; otherwise, any T, any N, or any M stage) and no prior malignancy. All patients underwent molecular profiling with the CIT256 and PAM50 molecular profile. RESULTS. In the study period, 2,816 patients were included in the CBCGS. Molecular subtyping showed an increase in nonluminal (molecular-apocrine, luminal C, and Basal-like) as compared with luminal (luminal A, luminal B, and Normal-like) subtypes with increasing stage from I to IV. Across all stages, we found a significant difference in survival among subtypes; 91% of patients with LumA were alive at 5 years compared with 91% for LumB, 84% for LumC, 82% for mApo, and 80% for Basal-like. We identified 442 tumors (16%) that were discordant in subtype between CIT256 and IHC. Discordant subtype proved to be a risk factor of death among patients with IHC luminal breast cancer (hazard ratio [HR], 2.08; 95% CI, 1.51–2.86) in a multivariable Cox regression analysis. Discordance occurred more often among patients with N3, stage IV, or grade III disease. CONCLUSION. Our findings indicate that molecular subtypes are a predominant classification for survival. Assessment is particularly crucial for patients with IHC luminal breast cancer with known high-risk factors, since they are at an increased risk of harboring an aggressive molecular subtype.
U2 - 10.1172/jci.insight.178114
DO - 10.1172/jci.insight.178114
M3 - Journal article
C2 - 38587073
AN - SCOPUS:85189833841
VL - 9
JO - JCI Insight
JF - JCI Insight
SN - 2379-3708
IS - 7
M1 - e178114
ER -
ID: 388788887