Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b

Snell, Cameron; Gough, Madeline; Liu, Cheng; Middleton, Kathryn; Pyke, Chris; Shannon, Catherine; Woodward, Natasha; Hickey, Theresa E.; Armes, Jane E.; Tilley, Wayne D.

doi:10.1038/s41416-018-0331-3

Cited by 9 publications

(9 citation statements)

References 52 publications

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“…For this reason, PgR absence may be due, at least in part, to the presence of a non-functional ER. 7,32 This fact could explain why the subgroup of PgR– BC has a lower response to endocrine therapies. 31 A recent study examined the clinical and biological features of BC women stratified according to ER and PgR tumor expression as double positive (ER+, PgR+), single positive (ER+, PgR–) and double negative (ER–, PgR–).…”

Section: Discussionmentioning

confidence: 99%

Role of androgen receptor expression in early stage ER+/PgR−/HER2– breast cancer

et al. 2020

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Background: Progesterone receptor (PgR) negative breast cancer (BC) is an aggressive subtype with poor prognosis and reduced response to endocrine treatments. Several studies have suggested that androgen receptor (AR) expression is associated with a favorable tumor biology, longer recurrence free survival (RFS), and overall survival. In the literature no data exist regarding the role of AR expression in early stage estrogen receptor (ER)+/PgR– BCs. The aim of this study was to evaluate the prognostic role of AR expression in this setting. Patients and methods: This is a monocentric retrospective study in which 208 patients who underwent surgical intervention for ER+/PgR−/Human Epidermal growth factor Receptor 2 (HER2)– BC were included. The primary objective was to analyze the relationship between AR expression and RFS. Results: At a median follow-up of 77 months, 75 patients (36%) had a disease relapse (all sites included). AR expression was significantly higher in patients who did not relapse compared with those who relapsed with an impact on RFS (hazard ratio [HR] = 0.99, p = 0.025). Patients with AR expression ⩾80% had a lower risk of relapse compared with those with AR <80% (HR = 0.53, p = 0.008). In addition, breast tumors with higher AR expression had good biological features (low ki67 and nuclear grade) compared with BCs with lower AR expression, at least partly explaining the different outcome. Conclusions: The results of this study support the potential prognostic role of AR in patients with ER+/PgR− BCs and may contribute to the identification of subgroups of high-risk patients.

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Section: Discussionmentioning

confidence: 99%

Role of androgen receptor expression in early stage ER+/PgR−/HER2– breast cancer

et al. 2020

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“…Aromatase is often expressed in human breast cancer tissues. Aromatase inhibition is the most effective endocrine treatment of postmenopausal women with ER-positive breast cancer [20].…”

Section: Steroid Hormones In Etiology Of Breast Cancermentioning

confidence: 99%

Breast Cancer: Targeting of Steroid Hormones in Cancerogenesis and Diagnostics

Valko-Rokytovská

Očenáš

Salayová

et al. 2021

IJMS

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Breast cancer is the most common malignancy in women with high mortality. Sensitive and specific methods for the detection, characterization and quantification of endogenous steroids in body fluids or tissues are needed for the diagnosis, treatment and prognosis of breast cancer and many other diseases. At present, non-invasive diagnostic methods are gaining more and more prominence, which enable a relatively fast and painless way of detecting many diseases. Metabolomics is a promising analytical method, the principle of which is the study and analysis of metabolites in biological material. It represents a comprehensive non-invasive diagnosis, which has a high potential for use in the diagnosis and prognosis of cancers, including breast cancer. This short review focuses on the targeted metabolomics of steroid hormones, which play an important role in the development and classification of breast cancer. The most commonly used diagnostic tool is the chromatographic method with mass spectrometry detection, which can simultaneously determine several steroid hormones and metabolites in one sample. This analytical procedure has a high potential in effective diagnosis of steroidogenesis disorders. Due to the association between steroidogenesis and breast cancer progression, steroid profiling is an important tool, as well as in monitoring disease progression, improving prognosis, and minimizing recurrence.

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“…Interestingly, it is speculated that tamoxifen resistance and the worse prognosis are associated solely with methylation of PGRA promoter, resulting in the functional predominance of PgR-B [ 57 ]. High frequency of ERα:PgR-B interaction was predictive of relapse on an adjuvant AI, and in some cases, a substantial amount of ERα:PgR-B interactions coexisted with a lack of IHC-detectable PgR expression [ 125 ].…”

Section: The Biology Of Erα(+)/pgr(−) Bcmentioning

confidence: 99%

Lost but Not Least—Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer

Kunc

Popęda

Biernat

et al. 2021

Cancers

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Estrogen receptor α (ERα) and progesterone receptor (PgR) are crucial prognostic and predictive biomarkers that are usually co-expressed in breast cancer (BC). However, 12–24% of BCs present ERα(+)/PgR(−) phenotype at immunohistochemical evaluation. In fact, BC may either show primary PgR(−) status (in chemonaïve tumor sample), lose PgR expression during neoadjuvant treatment, or acquire PgR(−) phenotype in local relapse or metastasis. The loss of PgR expression in ERα(+) breast cancer may signify resistance to endocrine therapy and poorer outcomes. On the other hand, ERα(+)/PgR(−) BCs may have a better response to neoadjuvant chemotherapy than double-positive tumors. Loss of PgR expression may be a result of pre-transcriptional alterations (copy number loss, mutation, epigenetic modifications), decreased transcription of the PGR gene (e.g. by microRNAs), and post-translational modifications (e.g. phosphorylation, sumoylation). Various processes involved in the down-regulation of PgR have distinct consequences on the biology of cancer cells. Occasionally, negative PgR status detected by immunohistochemical analysis is paradoxically associated with enhanced transcriptional activity of PgR that might be inhibited by antiprogestin treatment. Identification of the mechanism of PgR loss in each patient seems challenging, yet it may provide important information on the biology of the tumor and predict its responsiveness to the therapy.

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Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b

Cited by 9 publications

References 52 publications

Role of androgen receptor expression in early stage ER+/PgR−/HER2– breast cancer

Role of androgen receptor expression in early stage ER+/PgR−/HER2– breast cancer

Breast Cancer: Targeting of Steroid Hormones in Cancerogenesis and Diagnostics

Lost but Not Least—Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer

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