Discordance of the PAM50 Intrinsic Subtypes Compared with Immunohistochemistry-Based Surrogate in Breast Cancer Patients: Potential Implication of Genomic Alterations of Discordance

Kim, Hee Kyung; Park, Kyung Hee; Kim, Youjin; Park, Song Ee; Lee, Han Sang; Lim, Se-won; Cho, Jae Yong; Kim, Jiyeon; Lee, Jeong Eon; Ahn, Jin Seok; Im, Young‐Hyuck; Yu, Jong Han; Park, Yeon Hee

doi:10.4143/crt.2018.342

Cited by 65 publications

(60 citation statements)

References 34 publications

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“…Previous studies have shown significant discordance between clinical subtypes and intrinsic subtypes, which affects the prognosis of BRCA patients. Kim et al reported that discrepancies between the IHC-based subtype and the intrinsic subtype were associated with poor survival, highlighting the limitations of current IHC-based classification methods [30]. Consistent with previous results, we confirmed the poor survival of patients with non-matching subgroup classifications in both the TCGA and METABRIC datasets.…”

Section: Discussionsupporting

confidence: 91%

“…This discordance might be due to intratumoral heterogeneity, the coexistence of cells with different subtypes in the same tumor, as well as measurement inaccuracies in subtype profilers, IHC analysis for ER/PR status, and fluorescence in situ hybridization (FISH) analysis for HER2 status. These inconsistencies could result in administration of the wrong treatment, subsequently leading to poor survival [30]. Therefore, accurate identification of receptor status or the intrinsic BRCA subtype is of high clinical importance.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hormone Receptor-status Prediction in Breast Cancer Using Gene Expression Profiles and Their Macroscopic Landscape

Yoon¹,

Won

Kang³

et al. 2020

Preprint

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AbstractThe cost of next-generation sequencing technologies is rapidly declining, making RNA-seq-based gene expression profiling (GEP) an affordable technique for predicting receptor expression status and intrinsic subtypes in breast cancer (BRCA) patients. Based on the expression levels of co-expressed genes, GEP-based receptor-status prediction can classify clinical subtypes more accurately than can immunohistochemistry (IHC). Using data from the cancer genome atlas TCGA BRCA and METABRIC datasets, we identified common predictor genes found in both datasets and performed receptor-status prediction based on these genes. By assessing the survival outcomes of patients classified using GEP- or IHC-based receptor status, we compared the prognostic value of the two methods. We found that GEP-based HR prediction provided higher concordance with the intrinsic subtypes and a stronger association with treatment outcomes than did IHC-based hormone receptor (HR) status. GEP-based prediction improved the identification of patients who could benefit from hormone therapy, even in patients with non-luminal BRCA. We also confirmed that non-matching subgroup classification affected the survival of BRCA patients and that this could be largely overcome by GEP-based receptor-status prediction. In conclusion, GEP-based prediction provides more reliable classification of HR status, improving therapeutic decision making for breast cancer patients.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Hormone Receptor-status Prediction in Breast Cancer Using Gene Expression Profiles and Their Macroscopic Landscape

Yoon¹,

Won

Kang³

et al. 2020

Preprint

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show abstract

“…In our study, cohort 1 was divided into six subtypes based on IHC and ISH. Although it has been shown that surrogate markers can be used for molecular subtyping [24][25][26][27], there is a discrepancy between molecular subtype defined by surrogate markers and subtypes defined by gene expression analyses [28,29]. Nevertheless, similar to Gatza et al, we only found MRPS23 amplified cases among the non-basal tumours.…”

Section: Discussionsupporting

confidence: 59%

MRPS23 amplification and gene expression in breast cancer; association with proliferation and the non-basal subtypes

Klæstad

Opdahl

Engstrøm

et al. 2020

Breast Cancer Res Treat

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Purpose MRPS23 is recognized as a driver of proliferation in luminal breast cancer. The aims of the present study were to describe MRPS23 copy number change in breast cancer, and to assess associations between MRPS23 copy number change and molecular subtype, proliferation and prognosis, and between MRPS23 gene expression and molecular subtype and prognosis. Methods Using fluorescence in situ hybridization (FISH), we examined MRPS23 and centromere 17 copy number in 590 formalin-fixed, paraffin-embedded primary tumours and 144 corresponding lymph node metastases from a cohort of Norwegian breast cancer patients. Furthermore, we analysed MRPS23 gene expression data in 1971 primary breast cancer tumours from the METABRIC dataset. We used Pearson's χ 2 test to assess associations between MRPS23 copy number and molecular subtype and proliferation, and between MRPS23 expression and molecular subtype. We studied prognosis by estimating hazard ratios and cumulative incidence of death from breast cancer according to MRPS23 copy number and MRPS23 expression status. Results We found MRPS23 amplification (mean MRPS23 copy number ≥ 6 and/or MRPS23/chromosome 17 ratio ≥ 2) in 8% of primary tumours. Copy number increase associated with non-basal subtypes and higher tumour cell proliferation (Ki67). Higher MRPS23 expression associated with the Luminal B subtype. We found no significant association between MRPS23 amplification or MRSP23 gene expression, and prognosis. Conclusion Amplification of MRPS23 is associated with higher proliferation and non-basal subtypes in breast cancer. High MRPS23 expression is associated with the Luminal B subtype.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…Veeraraghavan et al found that a clinical subtype in breast cancer with high HER2 amplification and an intact PI3K pathway has a better response to anti-HER2 therapies without chemotherapy [19]. e findings of Kim et al showed that discordance between IHC-based subtypes and PAM50-based intrinsic subtypes was related to inadequate treatment and diminished survival in BC [20]. Studies also indicated that the percentage of stromal tumor-infiltrating lymphocytes (TILs) was associated with a higher pCR rate and improved survival in patients with HER2 + BC [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Dual HER2 Blockade versus a Single Agent in Trastuzumab-Containing Regimens for HER2-Positive Early Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

et al. 2020

Journal of Oncology

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Purpose. Although trastuzumab is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), drug resistance and disease relapse occur. erefore, we performed a meta-analysis to assess the efficacy and safety of trastuzumab-containing dual anti-HER2 therapy compared to trastuzumab alone. Methods. A systematic search was performed to identify eligible randomized controlled trials (RCTs). Main outcomes including event-free survival/invasive disease-free survival (EFS/iDFS), overall survival (OS), and safety were considered. Results. Ten RCTs were included (15,284 patients). Significant improvements were observed in both EFS/iDFS (HR 0.86, p � 0.0003) and OS (HR 0.86, p � 0.02) with trastuzumab-based dual anti-HER2 therapy, especially in adjuvant treatment, while in the neoadjuvant setting, dual-targeted therapy also achieved a substantial pathological complete response (pCR) benefit (HR 1.34, p � 0.0002). Subgroup analysis revealed that the EFS/iDFS benefit was slightly higher with trastuzumab plus pertuzumab or plus neratinib than trastuzumab plus lapatinib, while OS benefit was significant with trastuzumab plus lapatinib, but there were no subgroup differences (interaction test, p � 0.80 and 0.24, resp.). In addition, EFS/iDFS benefit was unrelated to hormone receptor status but pronounced in the lymph node-positive (LN+) subgroup, which should be interpreted cautiously for lacking interaction (p � 0.18). Besides, patients receiving dual therapy, especially with the lapatinib-containing regimen, experienced more toxicity, but no increase in cardiotoxicity. Conclusions. Despite being associated with more toxicity, trastuzumab-containing dual anti-HER2 therapy is superior to trastuzumab single agent for HER2-positive EBC independent of hormone receptor status. e correlation between survival and LN status needs further verification. Trastuzumab plus pertuzumab or plus neratinib is the preferred regimen with substantial efficacy and lower toxicity.

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Discordance of the PAM50 Intrinsic Subtypes Compared with Immunohistochemistry-Based Surrogate in Breast Cancer Patients: Potential Implication of Genomic Alterations of Discordance

Cited by 65 publications

References 34 publications

Hormone Receptor-status Prediction in Breast Cancer Using Gene Expression Profiles and Their Macroscopic Landscape

Hormone Receptor-status Prediction in Breast Cancer Using Gene Expression Profiles and Their Macroscopic Landscape

MRPS23 amplification and gene expression in breast cancer; association with proliferation and the non-basal subtypes

Dual HER2 Blockade versus a Single Agent in Trastuzumab-Containing Regimens for HER2-Positive Early Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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