Endocrine therapy for ER-positive/HER2-negative metastatic breast cancer

Reinert, Tomás; Paula, Bruno de; Shafaee, Maryam Nemati; Souza, Pedro Henrique de; Ellis, Matthew J.; Bines, José

doi:10.21037/cco.2018.06.06

Cited by 29 publications

(18 citation statements)

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“…Tamoxifen is the most commonly used SERM treatment and is mostly recommended for premenopausal women (38). It has shown a 31% reduction in the five-year mortality rate among hormone receptor-positive women (39) and around 500,000 women are alive today as a result of tamoxifen therapy alone (40). Aromatase inhibitors are competitive inhibitors of the aromatase enzyme and inhibit the synthesis of estrogen.…”

Section: Endocrine Therapy and Mechanism Of Actionmentioning

confidence: 99%

Molecular Mechanisms of Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer

Belachew

Sewasew

2021

Front. Endocrinol.

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The estrogen receptor is a vital receptor for therapeutic targets in estrogen receptor-positive breast cancer. The main strategy for the treatment of estrogen receptor-positive breast cancers is blocking the estrogen action on estrogen receptors by endocrine therapy but this can be restricted via endocrine resistance. Endocrine resistance occurs due to both de novo and acquired resistance. This review focuses on the mechanisms of the ligand-dependent and ligand-independent pathways and other coregulators, which are responsible for endocrine resistance. It concludes that combinatorial drugs that target different signaling pathways and coregulatory proteins together with endocrine therapy could be a novel therapeutic modality to stop endocrine resistance.

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Section: Endocrine Therapy and Mechanism Of Actionmentioning

confidence: 99%

Molecular Mechanisms of Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer

Belachew

Sewasew

2021

Front. Endocrinol.

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“…We are currently moving toward the era of personalized treatment, which is why knowledge regarding TNM stage and histopathological grading alone, although it supplies independent prognostic information, is inadequate for optimum patient treatment. Consequently, molecular biomarkers, such as ER and PR status, can provide prognostic information and additionally predict the response to therapy, and they have therefore become the center of research [7,33,34,35,36,37,38,39,40,41,42].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, these regimes are currently, according to National Comprehensive Cancer Network (NCCN) guidelines, an indispensable part of the adjuvant therapy for women with hormone receptor-positive (HR+) BC [2,3]. Clinical studies have confirmed that a high HR expression, such as estrogen receptor (ER), progesterone receptor (PR), and vitamin D receptor (VDR), increases the course of the disease [4,5,6,7,8]. In this study, we decided to further investigate the above-mentioned HR expressions, all being nuclear receptors, activated by their steroid hormones and being important targets for both prevention and treatment of BC.…”

Section: Introductionmentioning

confidence: 99%

Hormone Receptor Expression in Multicentric/Multifocal versus Unifocal Breast Cancer: Especially the VDR Determines the Outcome Related to Focality

Zehni

Jacob

Mumm

et al. 2019

IJMS

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The aim of this study was to evaluate the prognostic impact that hormone receptor (HR) expressions have on the two different breast cancer (BC) entities—multifocal versus unifocal BC. As the prognosis determining aspects, we investigated the overall survival (OS) and disease-free survival (DFS) by univariate and multivariate analysis. To underline the study’s conclusions, we additionally considered the histopathological grading and the tumor node metastasis (TNM) staging. A retrospective analysis was performed on survival-related events in a series of 320 breast cancer patients treated at the Department of Gynecology and Obstetrics at the Ludwig Maximillian University in Munich between 2000 and 2002. All three steroid receptors analyzed by immunohistochemistry, namely, the estrogen receptor (ER), the progesterone receptor (PR), and the vitamin D receptor (VDR), showed a significantly positive influence on the course of the disease, but only for the unifocal breast tumor patients. The prognosis of patients with multifocal breast cancer was either not affected by estrogen and/or progesterone receptor expression or even involved a worse etiopathology for the vitamin D receptor-positive patients. The estrogen receptor in unifocal breast cancer and the vitamin D receptor in multifocal breast cancer were especially identified as an independent prognostic marker for overall survival, when adjusted for age, grading, and staging. Altogether, our results strengthen the need to further investigate the behavior of the hormone receptors in breast cancer and understand why they have different effects on each focality type. Moreover, the studies for an adopted vitamin D supplementation due to breast cancer focality type must be enlarged to fully comprehend the remarkable and interesting role played by the vitamin D receptor.

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“…Endocrine therapy regimes led to a decline in the BC-associated mortality rate of approximately 30%, which makes them indispensable for the treatment of hormone-receptor-positive (HR+) BC [9][10][11]. Furthermore, clinical trials indicate a strong correlation between the expression of "classical steroid hormone receptors", such as ER and PR, and the progression of the disease [12][13][14][15][16]. Nevertheless, some tumors are resistant to those established therapeutic options, so the identification of new therapeutic targets is consequently central to research interests [17].…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer

Zehni

Batz

Cavaillès

et al. 2021

Cancers

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The aim of this retrospective study was to assess the prognostic value of cytoplasmic versus nuclear RXRα expression in breast cancer (BC) tissue samples and to correlate the results with clinicopathological parameters. In 319 BC patients, the expression of RXRα was evaluated via immunohistochemistry. Prognosis-determining aspects were calculated through uni- and multivariate analyses. Correlation analysis revealed a trend association with nuclear RXRα expression regarding an improved overall survival (OS) (p = 0.078), whereas cytoplasmic RXRα expression was significantly correlated with a poor outcomes in terms of both OS (p = 0.038) and disease-free survival (DFS) (p = 0.037). Strengthening these results, cytoplasmic RXRα was found to be an independent marker for DFS (p = 0.023), when adjusted to clinicopathological parameters, whereas nuclear RXRα expression was positively associated with lower TNM-staging, i.e., pT (p = 0.01), pN (p = 0.029) and pM (p = 0.001). Additionally, cytoplasmic RXRα expression was positively associated with a higher histopathological tumor grading (p = 0.02). Cytoplasmic RXRα was also found to be a negative prognosticator for Her-2neu-negative and triple-negative patients. Altogether, these findings support the hypothesis that the subcellular localization of RXRα plays an important role in carcinogenesis and the prognosis of BC. The expression of cytoplasmic RXRα is correlated with a more aggressive course of the disease, whereas nuclear RXRα expression appears to be a protective factor. These data may help to identify high-risk BC subgroups in order to find possible specific options in targeted tumor therapy.

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Endocrine therapy for ER-positive/HER2-negative metastatic breast cancer

Cited by 29 publications

References 0 publications

Molecular Mechanisms of Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer

Molecular Mechanisms of Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer

Hormone Receptor Expression in Multicentric/Multifocal versus Unifocal Breast Cancer: Especially the VDR Determines the Outcome Related to Focality

Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer

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