Abstract
PurposeEstrogen-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.MethodsWe 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.ResultsBreast 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.ConclusionThe 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.
Highlights
Estrogen, progesterone, and HER2 receptor statuses are important factors influencing breast cancer progression and have served as cornerstones for breast cancer classification and treatment
Testing occurred between January 2015 and February 2018. We reviewed another cohort composed of consecutive cases of individuals who had a prior diagnosis of breast cancer and pursued genetic high-risk cancer screening and surveillance in the Moffitt Cancer Center (MCC) GeneHome clinic between March 2017 and September 2020 after being found to carry germline cancer predisposition pathogenic variant (PV)
Among breast cancer developed in PV and non-PV carriers, ER and PR staining levels demonstrated very wide ranges of dispersion
Summary
Progesterone, and HER2 receptor statuses are important factors influencing breast cancer progression and have served as cornerstones for breast cancer classification and treatment. Genomic instability has risen as a predictor of cancer outcomes and offers opportunity for targeted treatment. In a large cohort of breast cancer patients, genome instability. A number of breast cancer predisposition genes (ATM, BRCA1, BRCA2, CHEK2, TP53, and PALB2) are important gatekeepers to maintaining DNA replication fidelity by regulating DNA damage repair. ER and PR expression in breast cancer have primarily been studied via binomial comparisons, ER-positive (ER +) and ER-negative (ER-). Because estrogen is a key regulator of progesterone receptor synthesis in mammary tissue, the exact expression level of PR is often overlooked. It is possible that differences in levels of ER and PR expression may lead to differential treatment responses and survival outcomes PR levels can be quite variable even when ER is strongly expressed in breast tumor cells and the expression levels for both ER and PR can vary greatly in a tumor designated “ER/PR positive.” It is possible that differences in levels of ER and PR expression may lead to differential treatment responses and survival outcomes
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