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. 2024 Jun 19;12(6):1361.
doi: 10.3390/biomedicines12061361.

BRCA1, BRCA2 and PALB2 mRNA Expression as Prognostic Markers in Patients with Early Breast Cancer

Ina Shehaj  1 , Slavomir Krajnak  1 , Katrin Almstedt  1 , Yaman Degirmenci  1 , Sophia Herzog  1 , Antje Lebrecht  1 , Valerie Catherine Linz  1 , Roxana Schwab  1 , Kathrin Stewen  1 , Walburgis Brenner  1 , Annette Hasenburg  1 , Marcus Schmidt  1 , Anne-Sophie Heimes  1
Affiliations

BRCA1, BRCA2 and PALB2 mRNA Expression as Prognostic Markers in Patients with Early Breast Cancer

Ina Shehaj et al. Biomedicines. .

Abstract

Breast cancer (BC) poses a challenge in establishing new treatment strategies and identifying new prognostic and predictive markers due to the extensive genetic heterogeneity of BC. Very few studies have investigated the impact of mRNA expression of these genes on the survival of BC patients.

Methods: We examined the impact of the mRNA expression of breast cancer gene type 1 (BRCA1), breast cancer gene type 2 (BRCA2), and partner and localizer of BRCA2 (PALB2) on the metastasis-free survival (MFS) of patients with early BC using microarray gene expression analysis.

Results: The study was performed in a cohort of 461 patients with a median age of 62 years at initial diagnosis. The median follow-up time was 147 months. We could show that the lower expression of BRCA1 and BRCA2 is significantly associated with longer MFS (p < 0.050). On the contrary, the lower expression of PALB2 was correlated with a shorter MFS (p = 0.049). Subgroup survival analysis identified the prognostic influence of mRNA expression for BRCA1 among patients with luminal-B-like BC and for BRCA2 and PALB2 in the subset of patients with luminal-A-like BC (p < 0.050).

Conclusions: According to our observations, BRCA1, BRCA2, and PALB2 expression might become valuable biomarkers of disease progression.

Keywords: BRCA1; BRCA2; PALB2; breast cancer; mRNA expression; metagene.

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Conflict of interest statement

A.-S. Heimes received honoraria from Pfizer Pharma GmbH, Roche Pharma AG, Daiichy Sankyo GmbH, Medupdate GmbH, and Streamedup! GmbH. K. Almstedt received speaker honoraria from Roche Pharma AG, Pfizer Pharma GmbH, and AstraZeneca. K. Stewen received honoraria from Astra Zeneca, Roche Pharma AG, StreamedUp! GmbH, and Pierre Fabre. I. Shehaj received funding and travel reimbursement from Olympus and AURIKAMED. R. Schwab received honoraria from Roche Pharma AG, AstraZeneca, and Streamedup! GmbH. S. Krajnak received speaker honoraria from Roche Pharma AG and Novartis Pharma GmbH Germany, research funding from Novartis Pharma GmbH Germany and travel reimbursement from PharmaMar and Novartis Pharma GmbH Germany. A. Hasenburg received honoraria from AstraZeneca, Celgen, GSK, LEO Pharma, MedConcept GmbH, Med update GmbH, Medicultus, Pfizer, Promedicis GmbH, Softconsult, Roche Pharma AG, Streamedup!GmbH, and Tesaro Bio Germany GmbH. She is a member of the advisory board of AstraZeneca, GSK, LEO Pharma, PharmaMar, Promedicis GmbH, Roche Pharma AG, Tesaro Bio Germany GmbH, MSD Sharp and Dohme GmbH. M. Schmidt reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche, and SeaGen outside the submitted work. Institutional research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, Marcus Schmidt has a patent for EP 2390370 B1 issued and a patent for EP 2951317 B1 issued. All other authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier analysis of metastasis-free survival in patients with early breast cancer according to the levels of BRCA1 metagene mRNA expression. BRCA1—breast cancer 1; p-value < 0.05 is considered to be significant.
Figure 2
Figure 2
Kaplan–Meier analysis of metastasis-free survival in patients with early breast cancer according to the levels of BRCA2 metagene mRNA expression. Abbreviations: BRCA2—breast cancer 2; p-value < 0.05 is considered to be significant.
Figure 3
Figure 3
Kaplan–Meier analysis of metastasis-free survival in patients with early breast cancer according to the levels of PALB2 mRNA expression. Abbreviations: PALB2—partner and localizer of BRCA2; BRCA2—breast cancer 2, p-value < 0.05 is considered to be significant.
Figure 4
Figure 4
Kaplan–Meier analysis of metastasis-free survival in patients with early breast cancer according to BRCA1 metagene mRNA expression. Abbreviations: BRCA1—breast cancer 1; luminal-A-like—estrogen receptor positive, HER2-negative, and low proliferation (AURKA-low); Luminal-B-like—estrogen receptor positive, HER2-negative, and high proliferation (AURKA-high); p-value < 0.05 is considered to be significant.
Figure 5
Figure 5
Kaplan–Meier analysis of metastasis-free survival in patients with early breast cancer according to BRCA2 metagene mRNA expression. Abbreviations: BRCA2—breast cancer 2; luminal-A-like—estrogen receptor positive, HER2-negative, and low proliferation (AURKA-low); luminal-B-like—estrogen receptor positive, HER2-negative, and high proliferation (AURKA-high); p-value < 0.05 is considered to be significant.
Figure 6
Figure 6
Kaplan–Meier analysis of metastasis-free survival in patients with early breast cancer according to PALB2 Metagene mRNA expression.
See this image and copyright information in PMC

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