The Prediction Analysis of Microarray 50 (PAM50) Gene Expression Classifier Utilized in Indeterminate-Risk Breast Cancer Patients in Hungary: A Consecutive 5-Year Experience

Author:

Dank Magdolna1ORCID,Mühl Dorottya1,Pölhös Annamária1,Csanda Renata1,Herold Magdolna12ORCID,Kovacs Attila Kristof3,Madaras Lilla3,Kulka Janina3,Palhazy Timea4,Tokes Anna-Maria3,Toth Monika5,Ujhelyi Mihaly6ORCID,Szasz Attila Marcell1ORCID,Herold Zoltan1ORCID

Affiliation:

1. Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, H-1083 Budapest, Hungary

2. Department of Internal Medicine and Hematology, Semmelweis University, H-1088 Budapest, Hungary

3. Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, H-1091 Budapest, Hungary

4. Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, H-1082 Budapest, Hungary

5. Department of Radiology, Semmelweis University, H-1082 Budapest, Hungary

6. TritonLife Medical Center, H-1135 Budapest, Hungary

Abstract

Background: Breast cancer has been categorized into molecular subtypes using immunohistochemical staining (IHC) and fluorescence in situ hybridization (FISH) since the early 2000s. However, recent research suggests that gene expression testing, specifically Prosigna® Prediction Analysis of Microarray 50 (PAM50), provides more accurate classification methods. In this retrospective study, we compared the results of IHC/FISH and PAM50 testing. We also examined the impact of various PAM50 parameters on overall survival (OS) and progression-free survival (PFS). Results: We analyzed 42 unilateral breast cancer samples, with 18 classified as luminal A, 10 as luminal B, 8 as Human epidermal growth factor receptor 2 (HER2)-positive, and 6 as basal-like using PAM50. Interestingly, 17 out of the 42 samples (40.47%) showed discordant results between histopathological assessment and the PAM50 classifier. While routine IHC/FISH resulted in classification differences for a quarter to a third of samples within each subtype, all basal-like tumors were misclassified. Hormone receptor-positive tumors (hazard rate: 8.7803; p = 0.0085) and patients who had higher 10-year recurrence risk scores (hazard rate: 1.0539; p = 0.0201) had shorter OS and PFS. Conclusions: Our study supports the existing understanding of molecular subtypes in breast cancer and emphasizes the overlap between clinical characteristics and molecular subtyping. These findings underscore the value of gene expression profiling, such as PAM50, in improving treatment decisions for breast cancer patients.

Publisher

MDPI AG

Subject

Genetics (clinical),Genetics

Reference50 articles.

1. World Health Organization (2023, May 10). Breast Cancer, Available online: https://www.who.int/cancer/prevention/diagnosis-screening/breast-cancer/en/.

2. American Cancer Society (2023, May 10). Breast Cancer Facts & Figures 2021–2022. Available online: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2021-2022.pdf.

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4. Repeated observation of breast tumor subtypes in independent gene expression data sets;Sorlie;Proc. Natl. Acad. Sci. USA,2003

5. Heterogeneity in hormone receptor status in primary and metastatic breast cancer;Osborne;Semin. Oncol.,1985

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