The impact of xenoestrogens on effectiveness of treatment for hormone-dependent breast cancer  – current state of knowledge and perspectives for research

Boszkiewicz, Kamila; Sawicka, Ewa; Piwowar, Agnieszka

doi:10.26444/aaem/124165

Cited by 5 publications

(3 citation statements)

References 49 publications

(72 reference statements)

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“…This may have significance for breast cancer in that S-(-)equol producer status has been linked to lower breast cancer risk [89]; however, further studies are needed to evaluate the bacterial metabolism of soy isoflavones in breast cancer patients whose tumors contain distinct estrogen receptor profiles. In summary, while there are obviously considerable commercial drivers behind the popular usage of dietary soy isoflavones as antioxidants and anti-inflammatory agents, their potential to counteract or modulate endocrine responses remains a concern [90,91].…”

Section: Human Exposure To Environmental Estrogens and Implications F...mentioning

confidence: 99%

The G Protein-Coupled Estrogen Receptor (GPER): A Critical Therapeutic Target for Cancer

Hall,

Filardo

2023

Cells

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Estrogens have been implicated in the pathogenesis of various cancers, with increasing concern regarding the overall rising incidence of disease and exposure to environmental estrogens. Estrogens, both endogenous and environmental, manifest their actions through intracellular and plasma membrane receptors, named ERα, ERβ, and GPER. Collectively, they act to promote a broad transcriptional response that is mediated through multiple regulatory enhancers, including estrogen response elements (EREs), serum response elements (SREs), and cyclic AMP response elements (CREs). Yet, the design and rational assignment of antiestrogen therapy for breast cancer has strictly relied upon an endogenous estrogen–ER binary rubric that does not account for environmental estrogens or GPER. New endocrine therapies have focused on the development of drugs that degrade ER via ER complex destabilization or direct enzymatic ubiquitination. However, these new approaches do not broadly treat all cancer-involved receptors, including GPER. The latter is concerning since GPER is directly associated with tumor size, distant metastases, cancer stem cell activity, and endocrine resistance, indicating the importance of targeting this receptor to achieve a more complete therapeutic response. This review focuses on the critical importance and value of GPER-targeted therapeutics as part of a more holistic approach to the treatment of estrogen-driven malignancies.

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Section: Human Exposure To Environmental Estrogens and Implications F...mentioning

confidence: 99%

The G Protein-Coupled Estrogen Receptor (GPER): A Critical Therapeutic Target for Cancer

Hall,

Filardo

2023

Cells

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“…Furthermore, the majority of breast cancers are hormone-dependent, 21 and hormones could stimulate cancer cell growth by interacting with respective receptors 22 including estrogen receptors, progesterone receptors, glucocorticoid receptors (GR), and androgen receptors. 23,24 Recent research showed that GR was found to be highly expressed in breast cells.…”

Section: Introductionmentioning

confidence: 99%

Enhancing the Inhibition of Breast Cancer Growth Through Synergistic Modulation of the Tumor Microenvironment Using Combined Nano-Delivery Systems

Wu,

Lu,

Zhao

et al. 2024

IJN

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“…Breast cancer is the most common cancer in women, affecting 2.1 million women worldwide each year and causing the largest number of cancer-related deaths in women [ 1 ]. According to the data providing by American Cancer Society, 13% of women will develop breast cancer in their lifetime, and 3% of them will die from it [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Aromatase Inhibitors and Risk of Metabolic and Cardiovascular Adverse Effects in Breast Cancer Patients—A Systematic Review and Meta-Analysis

Boszkiewicz

Piwowar

Petryszyn

2022

JCM

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Aromatase inhibitors (AIs) have been considered first-line therapy for patients with hormone-dependent breast cancer due to their high efficacy and good tolerability. However, AIs are not free of adverse events, and studies show that therapy with AIs is associated with an increased risk of cardiovascular events and the development of insulin resistance and diabetes. We searched the Cochrane Central Register of Controlled Trials, PubMed and EMBASE up to 27 October 2020 for the prevalence of cardiovascular and/or metabolic adverse effects during treatment with AIs in postmenopausal women with breast cancer. A meta-analysis was performed using a random effects model. Odds ratios and 95% confidence intervals were calculated and illustrated using forest plot charts. We performed separate analyses depending on trial design. Twenty two studies met the inclusion criteria. AIs were associated with a higher risk of cardiovascular events, especially when we compared study arms in which AIs were used (alone or in sequence with TAM) with the arms in which TAM was used alone (OR = 1.16; 95%CI 1.04–1.30) or when comparing patients taking AIs alone to patients taking TAM alone or in sequence with AIs (OR = 1.24; 95%CI 1.11–1.38). A pooled analysis of five trials comparing adjuvant AIs to TAM showed the odds for arterial hypertension being 1.31 times higher for patients taking AIs; however, this did not reach statistical significance (OR = 1.31; 95%CI 0.47–3.65). We have not shown an increased risk of dyslipidemia or weight gain with the use of AIs. Our results suggest that postmenopausal women with breast cancer treated with AIs have an increased risk of cardiovascular events in comparison with TAM, potentially due more to a cardioprotective effect of the latter than the cardiotoxicity of AIs. We were unable to prove a similar association for hypertension, dyslipidemia, hyperglycemia or weight gain. Further high-quality RCTs and post-marketing safety observational studies are needed to definitively evaluate the impact of AIs on metabolic disorders in breast cancer patients.

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The impact of xenoestrogens on effectiveness of treatment for hormone-dependent breast cancer – current state of knowledge and perspectives for research

Cited by 5 publications

References 49 publications

The G Protein-Coupled Estrogen Receptor (GPER): A Critical Therapeutic Target for Cancer

The G Protein-Coupled Estrogen Receptor (GPER): A Critical Therapeutic Target for Cancer

Enhancing the Inhibition of Breast Cancer Growth Through Synergistic Modulation of the Tumor Microenvironment Using Combined Nano-Delivery Systems

Aromatase Inhibitors and Risk of Metabolic and Cardiovascular Adverse Effects in Breast Cancer Patients—A Systematic Review and Meta-Analysis

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