Skip to main content
Top
Published in: Breast Cancer Research 1/2022

Open Access 01-12-2022 | Breast Cancer | Research article

Unique ER PR expression pattern in breast cancers with CHEK2 mutation: a hormone receptor and HER2 analysis based on germline cancer predisposition genes

Authors: Grace Wei, Mingxiang Teng, Marilin Rosa, Xia Wang

Published in: Breast Cancer Research | Issue 1/2022

Login to get access

Abstract

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.
Literature
1.
go back to reference Lischka A, Doberstein N, Freitag-Wolf S, Kocak A, Gemoll T, Heselmeyer-Haddad K, et al. Genome instability profiles predict disease outcome in a cohort of 4,003 patients with breast cancer. Clin Cancer Res. 2020;26(17):4606–15.CrossRef Lischka A, Doberstein N, Freitag-Wolf S, Kocak A, Gemoll T, Heselmeyer-Haddad K, et al. Genome instability profiles predict disease outcome in a cohort of 4,003 patients with breast cancer. Clin Cancer Res. 2020;26(17):4606–15.CrossRef
2.
go back to reference Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5). Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5).
3.
go back to reference Arpino G, Weiss H, Lee AV, Schiff R, De Placido S, Osborne CK, et al. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst. 2005;97(17):1254–61.CrossRef Arpino G, Weiss H, Lee AV, Schiff R, De Placido S, Osborne CK, et al. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst. 2005;97(17):1254–61.CrossRef
4.
go back to reference Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med. 2009;15(8):907–13.CrossRef Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med. 2009;15(8):907–13.CrossRef
5.
go back to reference Sweeney C, Bernard PS, Factor RE, Kwan ML, Habel LA, Quesenberry CP Jr, et al. Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: differences by age, race, and tumor characteristics. Cancer Epidemiol Biomarkers Prev. 2014;23(5):714–24.CrossRef Sweeney C, Bernard PS, Factor RE, Kwan ML, Habel LA, Quesenberry CP Jr, et al. Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: differences by age, race, and tumor characteristics. Cancer Epidemiol Biomarkers Prev. 2014;23(5):714–24.CrossRef
6.
go back to reference Caan BJ, Sweeney C, Habel LA, Kwan ML, Kroenke CH, Weltzien EK, et al. Intrinsic subtypes from the PAM50 gene expression assay in a population-based breast cancer survivor cohort: prognostication of short- and long-term outcomes. Cancer Epidemiol Biomarkers Prev. 2014;23(5):725–34.CrossRef Caan BJ, Sweeney C, Habel LA, Kwan ML, Kroenke CH, Weltzien EK, et al. Intrinsic subtypes from the PAM50 gene expression assay in a population-based breast cancer survivor cohort: prognostication of short- and long-term outcomes. Cancer Epidemiol Biomarkers Prev. 2014;23(5):725–34.CrossRef
7.
go back to reference Joshi PA, Goodwin PJ, Khokha R. Progesterone exposure and breast cancer risk: understanding the biological roots. JAMA Oncol. 2015;1(3):283–5.CrossRef Joshi PA, Goodwin PJ, Khokha R. Progesterone exposure and breast cancer risk: understanding the biological roots. JAMA Oncol. 2015;1(3):283–5.CrossRef
8.
go back to reference Joshi PA, Jackson HW, Beristain AG, Di Grappa MA, Mote PA, Clarke CL, et al. Progesterone induces adult mammary stem cell expansion. Nature. 2010;465(7299):803–7.CrossRef Joshi PA, Jackson HW, Beristain AG, Di Grappa MA, Mote PA, Clarke CL, et al. Progesterone induces adult mammary stem cell expansion. Nature. 2010;465(7299):803–7.CrossRef
9.
go back to reference Chlebowski RT, Rohan TE, Manson JE, Aragaki AK, Kaunitz A, Stefanick ML, et al. Breast cancer after use of estrogen plus progestin and estrogen alone: analyses of data from 2 women’s health initiative randomized clinical trials. JAMA Oncol. 2015;1(3):296–305.CrossRef Chlebowski RT, Rohan TE, Manson JE, Aragaki AK, Kaunitz A, Stefanick ML, et al. Breast cancer after use of estrogen plus progestin and estrogen alone: analyses of data from 2 women’s health initiative randomized clinical trials. JAMA Oncol. 2015;1(3):296–305.CrossRef
10.
go back to reference Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomark Prevent. 2012;21(1):134–47.CrossRef Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomark Prevent. 2012;21(1):134–47.CrossRef
Metadata
Title
Unique ER PR expression pattern in breast cancers with CHEK2 mutation: a hormone receptor and HER2 analysis based on germline cancer predisposition genes
Authors
Grace Wei
Mingxiang Teng
Marilin Rosa
Xia Wang
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2022
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-022-01507-1

Other articles of this Issue 1/2022

Breast Cancer Research 1/2022 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine