Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review

Leptomeningeal disease (LMD) represents a devastating complication of advanced breast cancer (ABC), with survival of <5 months with multimodal treatment. The role of endocrine therapy (ET), due to its favorable toxicity profile and first-line indication in luminal ABC, appears promising in the setting of LMD, where symptom stabilization and quality-of-life preservation are the main goals; however, evidenced-based data are lacking. We conducted a thorough review of published evidence, aiming to investigate the role of ET in LMD treatment in luminal ABC. Twenty-one of 342 articles, evaluating 1302 patients, met inclusion criteria. ET use was rarely reported. New targeted agents show CNS activity. Research is lacking on the role of ET and targeted agents in BC-LMD treatment.

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Regulatory Interplay between miR-181a-5p and Estrogen Receptor Signaling Cascade in Breast Cancer

Cancers ◽

10.3390/cancers13030543 ◽

2021 ◽

Vol 13 (3) ◽

pp. 543

Author(s):

Rosaria Benedetti ◽

Chiara Papulino ◽

Giulia Sgueglia ◽

Ugo Chianese ◽

Tommaso De Marchi ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Endocrine Therapy ◽

Mirna Expression ◽

Estrogen Receptor Alpha ◽

Estrogen Signaling ◽

Integrated Analysis ◽

Tumor Resistance ◽

Estrogen Receptor Signaling

The efficacy and side effects of endocrine therapy in breast cancer (BC) depend largely on estrogen receptor alpha (ERα) expression, the specific drug administered, and treatment scheduling. Although the benefits of endocrine therapy outweigh any adverse effects in the initial stages of BC, later- or advanced-stage tumors acquire resistance to treatments. The mechanisms underlying tumor resistance to therapy are still not well understood, posing a major challenge for BC patient care. Epigenetic regulation and miRNA expression may be involved in the switch from a treatment-sensitive to a treatment-resistant state and could provide a valid therapeutic strategy for ERα negative BC. Here, a hybrid lysine-specific histone demethylase inhibitor, MC3324, displaying selective estrogen receptor down-regulator-like activities in BC, was used to highlight the interplay between epigenetic and ERα signaling. MC3324 anticancer action is mediated by microRNA (miRNA) expression regulation, indicating an innovative function for this molecule. Integrated analysis suggests a crosstalk between estrogen signaling, ERα interactors, miRNAs, and their putative targets. Specifically, miR-181a-5p expression is regulated by MC3324 and has an impact on cellular levels of ERα. A comparison of breast tumor versus healthy mammary tissues confirmed the important role of miR-181a-5p in ERα regulation and points to its putative predictive function in BC therapy.

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The Emerging Role of Extracellular Vesicles in Endocrine Resistant Breast Cancer

Cancers ◽

10.3390/cancers13051160 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1160

Author(s):

Giusi La Camera ◽

Luca Gelsomino ◽

Amanda Caruso ◽

Salvatore Panza ◽

Ines Barone ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Extracellular Vesicles ◽

Molecular Mechanisms ◽

Endocrine Resistance ◽

Disease Recurrence ◽

Estrogen Receptor Α ◽

Research Area ◽

Tumor Evolution

Breast cancer is the most common solid malignancy diagnosed in females worldwide, and approximately 70% of these tumors express estrogen receptor α (ERα), the main biomarker of endocrine therapy. Unfortunately, despite the use of long-term anti-hormone adjuvant treatment, which has significantly reduced patient mortality, resistance to the endocrine treatments often develops, leading to disease recurrence and limiting clinical benefits. Emerging evidence indicates that extracellular vesicles (EVs), nanosized particles that are released by all cell types and responsible for local and systemic intercellular communications, might represent a newly identified mechanism underlying endocrine resistance. Unraveling the role of EVs, released by transformed cells during the tumor evolution under endocrine therapy, is still an open question in the cancer research area and the molecular mechanisms involved should be better defined to discover alternative therapeutic approaches to overcome resistance. In this review, we will provide an overview of recent findings on the involvement of EVs in sustaining hormonal resistance in breast cancer and discuss opportunities for their potential use as biomarkers to monitor the therapeutic response and disease progression.

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