Abstract
Background
PALB2 plays a crucial role in genome stability and the DNA repair process, and its
mutation is associated with a moderate to high risk of breast cancer. However, the
status and prognostic role of PALB2 expression in breast cancer are still unclear.
Materials and Methods
The expression level of PALB2 mRNA was evaluated by using quantitative real-time polymerase
chain reaction in core biopsy samples from 563 primary breast cancer tissues.
Results
In the entire cohort, low expression of PALB2 mRNA was significantly associated with
poor survival (low vs. intermediate: DFS, adjusted HR=1.79, 95% CI=0.21-2.65, P=0.003; DDFS, adjusted HR=2.07,
95% CI=1.34-3.20, P=0.001; DSS, adjusted HR=2.59, 95% CI=1.45-4.64, P=0.001; OS, adjusted
HR=2.77, 95% CI=1.56-4.92, P=0.001; low vs. high: DFS, adjusted HR=1.57, 95% CI=1.06-2.35, P=0.026; DDFS, adjusted HR=1.66,
95% CI=1.08-2.55, P=0.020; DSS, adjusted HR=1.74, 95% CI=1.00-3.03, P=0.048; OS, adjusted
HR=1.59, 95% CI=0.95-2.67, P=0.08). Notably, among hormone receptor (HR)-positive/HER2-negative
subtype, patients with low PALB2 expression also had significantly worse outcomes
(low vs. intermediate: DFS, adjusted HR=2.33, 95% CI=1.32-4.13, P=0.004; DDFS, adjusted HR=2.78,
95% CI=1.47-5.27, P<0.001; DSS, adjusted HR=3.08, 95% CI=1.27-7.43, P= 0.013; OS,
adjusted HR=3.15, 95% CI=1.32-7.50, P=0.010; low vs. high: DFS, adjusted HR=1.84, 95% CI=1.04-3.28, P=0.04; DDFS, adjusted HR=1.82, 95%
CI=0.99-3.36, P=0.05; DSS, adjusted HR=2.06, 95% CI=0.87-4.86, P=0.10; OS, adjusted
HR=1.54, 95% CI=0.71-3.33, P=0.28).
Conclusion
Breast cancer patients with low expression of mRNA have a poor survival, suggesting
that patients with PALB2 low expression may be the potential beneficiaries for PARP
inhibitors therapy.
MicroAbstract
PALB2 plays a crucial role in genome stability and the DNA repair process. In the
current study, we found that patients with low expression level of PALB2 mRNA had
a poor prognosis in breast cancer.
Graphical Abstract

Graphical Abstract
Keywords
Abbreviations:
CI (confidence interval), HER2 (human epidermal growth factor receptor 2), HR (homologous recombination), PALB2 (partner and localizer of BRCA2), PARP (poly (ADP-ribose) polymerase), PCR (polymerase chain reaction)To read this article in full you will need to make a payment
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References
- Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer.JAMA Oncol. 2017; 3: 1190-1196
- PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene.Nat Genet. 2007; 39: 165-167
- PALB2/FANCN: recombining cancer and Fanconi anemia.Cancer Res. 2010; 70: 7353-7359
- Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2.Mol Cell. 2006; 22: 719-729
- PALB2 is an integral component of the BRCA complex required for homologous recombination repair.Proc Natl Acad Sci U S A. 2009; 106: 7155-7160
- PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2.Mol Cancer Res. 2009; 7: 1110-1118
- A PALB2 mutation associated with high risk of breast cancer.Breast Cancer Res. 2010; 12: R109
- Breast-cancer risk in families with mutations in PALB2.N Engl J Med. 2014; 371: 497-506
- PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.J Med Genet. 2016; 53: 800-811
- The contribution of pathogenic variants in breast cancer susceptibility genes to familial breast cancer risk.NPJ Breast Cancer. 2017; 3: 22
- Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.Nat Commun. 2018; 9: 4083
- Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.J Med Genet. 2017; 54: 732-741
- Mutation analysis of PALB2 gene in French breast cancer families.Breast Cancer Res Treat. 2015; 154: 463-471
- Evaluation of the need for routine clinical testing of PALB2 c.1592delT mutation in BRCA negative Northern Finnish breast cancer families.BMC Med Genet. 2013; 14: 82
- Clinical outcomes in women with breast cancer and a PALB2 mutation: a prospective cohort analysis.Lancet Oncol. 2015; 16: 638-644
- Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia.Breast Cancer Res Treat. 2017; 165: 687-697
- Spectrum and clinical relevance of PALB2 germline mutations in 7657 Chinese BRCA1/2-negative breast cancer patients.Breast Cancer Res Treat. 2020; 179: 605-614
- The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumor phenotype.Clin Cancer Res. 2009; 15: 3214-3222
- Germline mutations of PALB2 gene in a sequential series of Chinese patients with breast cancer.Breast Cancer Res Treat. 2017; 166: 865-873
- High BRCA2 Gene Expression is Associated with Aggressive and Highly Proliferative Breast Cancer.Ann Surg Oncol. 2021; 28: 7356-7365
- High BRCA1 gene expression increases the risk of early distant metastasis in ER(+) breast cancers.Sci Rep. 2022; 12: 77
- Predictive value of BRCA1/2 mRNA expression for response to neoadjuvant chemotherapy in BRCA-negative breast cancers.Cancer Sci. 2018; 109: 166-173
- Development and validation of molecular methodologies to assess PALB2 expression in sporadic breast cancer.Clin Biochem. 2016; 49: 253-259
- PALB2 upregulation is associated with a poor prognosis in pancreatic ductal adenocarcinoma.Oncol Lett. 2021; 21: 224
- High expression of PALB2 predicts poor prognosis in patients with advanced breast cancer.FEBS Open Bio. 2018; 8: 56-63
- PALB2 links BRCA1 and BRCA2 in the DNA-damage response.Curr Biol. 2009; 19: 524-529
- BRCAness revisited.Nat Rev Cancer. 2016; 16: 110-120
- PALB2 as a potential prognostic biomarker for colorectal cancer.Comput Biol Chem. 2020; 87107289
- PARP inhibitors: Synthetic lethality in the clinic.Science. 2017; 355: 1152-1158
- Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.Nat Struct Mol Biol. 2010; 17: 1247-1254
- PARP Inhibitors as a Therapeutic Agent for Homologous Recombination Deficiency in Breast Cancers.J Clin Med. 2019; 8
- TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.J Clin Oncol. 2020; 38: 4274-4282
- Challenges in the management of advanced, ER-positive, HER2-negative breast cancer.Nat Rev Clin Oncol. 2015; 12: 541-552
- Treating cancer with selective CDK4/6 inhibitors.Nat Rev Clin Oncol. 2016; 13: 417-430
- Cellular mechanisms underlying response and resistance to CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer.Breast Cancer Res. 2022; 24: 17
- Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer.Clin Cancer Res. 2011; 17: 1591-1602
Article info
Publication history
Accepted:
March 3,
2023
Received in revised form:
February 12,
2023
Received:
July 22,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.