• What is PGR?
  • PGR in Breast Cancer
  • PR Expression
  • Clinical Trials

PR (PGR)

The progesterone receptor gene (PGR, commonly known as PR) plays a role in pathogenesis of cancers such as endometrial cancer and breast cancer (Kim et al. 2013). PR is located on chromosome 11 (Law et al. 1987). PR is in the nuclear receptor superfamily, is part of the steroid receptor family, and has a six-region structure with a defined functional domain (Grontved and Hager 2012).

PR protein expression is measured using immunohistochemistry (IHC) and PR expression occurs in 55–58% of invasive breast cancers (Nadji et al. 2005; Rhodes et al. 2000) and in 50–72% of endometrial cancers (Merritt et al. 2010; Suthipintawong et al. 2008).

Related Pathways

Contributors: Justin M. Balko, Pharm. D., Ph.D., Ingrid A. Mayer, M.D., M.S.C.I., Mia Levy, M.D., Ph.D., Carlos L. Arteaga, M.D.

Suggested Citation: Balko, J., I. Mayer, M. Levy, C. Arteaga. 2015. PR (PGR). My Cancer Genome https://www.padiracinnovation.org/content/disease/breast-cancer/pgr/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

PR (PGR) in Breast Cancer

Progesterone receptor (PR) protein expression occurs in 55–58% of breast cancers (Nadji et al. 2005; Rhodes et al. 2000). PR (PGR) mutations are not known to be important in breast cancer.

Gene or Protein Invasive Breast Cancer Hormone Receptor Positive (ER+ and/or PR+) Invasive Breast Cancer HER2 positive Invasive Breast Cancer Triple-negative Invasive Breast Cancer
PR expression 55–58% (Nadji et al. 2005; Rhodes et al. 2000) 84% (Dunnwald et al. 2007) 50% (Blows et al. 2011 0%
NOTE: ER = estrogen receptor; PR = progesterone receptor

Testing for PR Expression in Breast Cancer

Because ER and PR expression is predictive for response with endocrine therapy and prognostic for survival outcomes, accurate immunohistochemistry (IHC) measurements for ER and PR expression in breast cancer are important (Hammond et al. 2010a).

Several different methods have been used to measure PR status. Per National Comprehensive Cancer Network (NCCN) guidelines, PR expression in invasive breast cancer or ductal carcinoma in situ (DCIS) tumor tissue should be measured with validated IHC assays (Allred et al. 2009). The ASCO/CAP guideline recommendations for ER and PR testing by IHC in breast cancer patients specify the following algorithm for optimal ER/PR testing (Hammond et al. 2010a; Hammond et al. 2010b):

 

1. Positive for ER or PR if finding of ≥ 1% of tumor cell nuclei are immunoreactive.

2. Negative for ER or PR if finding of < 1% of tumor cell nuclei are immunoreactive in the presence of evidence that the sample can express ER or PR (positive intrinsic controls are seen).

3. Uninterpretable for ER or PR if finding that no tumor nuclei are immunoreactive and that internal epithelial elements present in the sample or separately submitted from the same sample lack any nuclear staining.


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Contributors: Justin M. Balko, Pharm. D., Ph.D., Ingrid A. Mayer, M.D., M.S.C.I., Mia Levy, M.D., Ph.D., Carlos L. Arteaga, M.D.

Suggested Citation: Balko, J., I. Mayer, M. Levy, C. Arteaga. 2013. PR (PGR) in Breast Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/breast-cancer/pgr/ (Updated October 11).

Last Updated: October 11, 2013

PR (PGR) Expression in Breast Cancer

Properties
Location of mutation Not applicable
Frequency of PR expression in breast cancer 50% (Allred et al. 2009)
Implications for Targeted Therapeutics
Response to selective estrogen receptor modulators and antagonists Unknown at this timea
Response to aromatase inhibitors Unknown at this timeb

Progesterone receptor (PR) expression occurs in approximately half of breast cancer tumors (Allred et al. 2009). In patients that have ER-positive breast cancer, 83% are also PR-positive (Dunnwald et al. 2007).

a PR expression is associated with favorable prognosis in hormone-receptor positive breast cancer patients (Hammond et al. 2010). In an update of a meta-analysis of trials evaluating adjuvant tamoxifen, predictive benefit for ER but not PR was confirmed (EBCTCG 2011), consistent with several retrospective studies (Dowsett 2005; Dowsett 2006; Dowsett 2008; Viale 2007; Yamashita 2006). In breast cancer patients that are ER-negative and PR-positive, a clearer predictive role for PR status has been measured for adjuvant tamoxifen (Dowsett 2006; Dowsett 2013).

b In a large prospective substudy evaluating predictive biomarkers for adjuvant therapy with the aromatase inhibitor exemestane in comparison with tamoxifen in breast cancer patients, PR status was demonstrated to be prognostic and not predictive (TEAM substudy, Bartlett et al. 2011). This is consistent with results demonstrated in restrospective studies with the aromatase inhibitors anastazole and letrozole (Dowsett 2008; Viale 2007).

Contributors: Justin M. Balko, Pharm. D., Ph.D., Ingrid A. Mayer, M.D., M.S.C.I., Mia Levy, M.D., Ph.D., Carlos L. Arteaga, M.D.

Suggested Citation: Balko, J., I. Mayer, M. Levy, C. Arteaga. 2015. PR (PGR) Expression in Breast Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/breast-cancer/pgr/249/ (Updated June 18).

Last Updated: June 18, 2015

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