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Unique ER PR expression pattern in breast cancers with CHEK2 mutation: a hormone receptor and HER2 analysis based on germline cancer predisposition genes
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Unique ER PR expression pattern in breast cancers with CHEK2 mutation: a hormone receptor and HER2 analysis based on germline cancer predisposition genes
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Journal Article
Unique ER PR expression pattern in breast cancers with CHEK2 mutation: a hormone receptor and HER2 analysis based on germline cancer predisposition genes
2022
Overview
Purpose
Estrogen-receptor (ER) and progesterone-receptor (PR) expression levels in breast cancer, which have been principally compared via binomial descriptors, can vary widely across tumors. We sought to characterize ER and PR expression levels using semi-quantitative analyses of receptor staining in germline pathogenic variant (PV) carriers of cancer predisposition genes.
Methods
We conducted a retrospective chart review of patients who underwent germline genetic testing for cancer predisposition genes at a tertiary cancer center genetics clinic. We performed comparisons of semi-quantitative ER and PR percentage staining levels across carriers and non-carriers of cancer predisposition genes.
Results
Breast cancers from
BRCA1
PV carriers expressed significantly lower ER (15.2% vs 78.2%,
p
< 0.001) and lower PR (6.8% vs 41.1%,
p
< 0.001) staining compared to non-PV carriers. Similarly, breast cancers of
BRCA2
(66.7% vs 78.2%,
p
= 0.005) and
TP53
(50.6% vs 78.2%,
p
= 0.015) PV tumors also displayed moderate decreases in ER staining. Conversely,
CHEK2
tumors displayed higher ER (93.1% vs 78.2%,
p
= 0.005) and PR (72% vs 48.8%,
p
= 0.001) staining when compared to non-PV carriers. We observed a wide range of dispersion across the ER and PR staining levels of the carriers and noncarriers. ER and PR ranges of dispersion of
CHEK2
tumors were uniquely narrower than all other groups.
Conclusion
The findings of our study suggest that precise expression levels of ER and PR in breast cancers can vary widely. These differences are further augmented when comparing expression staining across PV and non-PV carriers, suggesting potentially unique tumorigenesis and progression pathways influenced by germline cancer predisposition genes.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Biomedical and Life Sciences
/ Breast Neoplasms - pathology
/ Cancer
/ Checkpoint Kinase 2 - genetics
/ Female
/ Genes
/ Genetic Predisposition to Disease
/ Germline cancer predisposition gene
/ HER2
/ Hormones
/ Humans
/ Melanoma
/ Mutation
/ Oncology
/ Patients
/ Receptors, Progesterone - genetics
/ Receptors, Progesterone - metabolism
/ Tumors
