scholarly journals A Case of Disease Improvement after Treatment with Everolimus plus Exemestane in a Patient with Hormone Receptor-Positive Metastatic Breast Cancer with Bone Metastases

2015 ◽  
Vol 8 (1) ◽  
pp. 101-105 ◽  
Author(s):  
J. Thaddeus Beck ◽  
Ryan Mantooth

Breast cancer is one of the most frequently diagnosed cancers and a leading cause of death in women worldwide. Despite significant advances in the treatment of hormone receptor-positive breast cancer, tumor metastasis occurs frequently and is associated with poor long-term prognosis. The mammalian target of rapamycin (mTOR) pathway plays a central role in cancer cell growth, proliferation, and resistance to endocrine therapies. Therefore, mTOR inhibitors such as everolimus in combination with nonsteroidal aromatase inhibitors might reverse endocrine resistance and improve clinical outcomes in patients. Here, we report on a case of infiltrating lobular carcinoma of the breast with metastases to the bone. Histopathologic analysis showed that the patient was estrogen and progesterone receptor positive and human epidermal growth factor-2 negative. This case represents the clinical spectrum of complications caused by metastasis: the patient experienced a considerable amount of skeletal-related complications, had previously received chemotherapy, and experienced disease progression while taking nonsteroidal aromatase inhibitors. After treatment with oral everolimus 10 mg daily plus oral exemestane 25 mg daily, the patient's disease was ameliorated. Combination therapy was well tolerated, with minimal adverse effects that were manageable with concomitant medications. Although further analyses in larger populations are necessary, the addition of everolimus to exemestane might provide an effective new treatment option for patients with bone metastasis.

2021 ◽  
Author(s):  
Nicholas P. McAndrew ◽  
Richard S. Finn

The natural history of hormone receptor–positive breast cancer tends to be more favorable than other subtypes such as human epidermal growth factor receptor 2–amplified and triple-negative. In addition, the natural dependence on steroid hormone signaling has allowed for therapeutic targeting of this pathway and significant improvements in survival while maintaining quality of life: the two main goals in management of the disease. The sequential use of endocrine agents including the selective estrogen receptor modulators (tamoxifen), aromatase inhibitors (letrozole, anastrozole, and exemestane) and the selective estrogen receptor degrader fulvestrant has been the backbone of management for years. In the past decade, the introduction of molecularly targeted agents against intracellular targets such as mammalian target of rapamycin (everolimus), cyclin-dependent kinases 4 and 6 (palbociclib, ribociclib, and abemaciclib), and phosphatidylinositol 3-kinase (alpelisib) has offered patients effective nonchemotherapy-based options, which are improving outcomes. Although knowledge gaps still exist in regard to the optimal sequencing of these new regimens, they have expanded our repertoire of options for patients and have shifted the need for cytotoxic chemotherapy and its associated complications to later lines. Still, formatting a plan for these patients includes taking into account traditional prognostic factors such as menopausal status, previous treatments, disease-free interval for those patients with early breast cancer that has recurred, and tumor burden. To assist in developing this treatment plan, we will review the current data with systemic agents in the management of these patients.


2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 5-5
Author(s):  
E. Aboelkheir* ◽  
A. Ashour ◽  
S. Fadel ◽  
W. Arafat

Introduction: The standard treatment of hormone receptor positive Her2 negative metastatic breast cancer is endocrine therapy with or without targeted therapy (e.g.CDK4/6inhibitors and mTOR inhibitors). Chemotherapy is indicated only in visceral crisis and the presence of visceral metastases is not indication for chemotherapy Aim of study The retrospective study aimed to characterize treatment and outcomes for patients with hormone receptor positive metastatic breast cancer in Alexandria clinical oncology department to review change in treatment trend during the last 10 years. Physician questionnaire to determine their preferences in choosing treatment. Methods Retrospective study using patient files of adult female diagnosed and treated at Clinical Oncology and Nuclear Medicine Department, Alexandria Main University Hospitals during the period from January 2010 to December 2019. Physician questionnaire was done by physician recruitment via online survey & scientific meetings. Results: The study identified 611 women with hormone receptor positive metastatic breast cancer, median age was 50years, 48.9% were postmenopausal, 56.7% of hormone receptor positive, Her2 negative patients received chemotherapy as first line systemic treatment, 69.5% of these patients received chemotherapy as first line treatment in the first 5years. But, 48.8% of these patients received chemotherapy as first line in the last 5years and the study showed that median overall survival for all studied patients was 34 months. In contrast, the physician questionnaire showed that 75% of physicians prefer endocrinal therapy as first line treatment for hormone receptor positive, Her2 negative metastatic breast cancer. Conclusion: There is significant change in practice pattern in choosing the first line treatment between the first and last 5 years. Also, there is a discrepancy between practice pattern and physician preferences in choosing the first line systemic treatment for hormone receptor positive, Her2 negative metastatic breast cancer. The reason is the unavailability of most targeted agents (e.g; CDK4/6 inhibitors and mTOR inhibitors) and some hormonal agents such as fulvestrant.


Author(s):  
Sheridan Wilson ◽  
Stephen K. Chia

Hormone receptor–positive (HR+) breast cancer is the most prevalent subtype of breast cancer in both early- and advanced-stage disease. Thus, the treatment of HR+ breast cancer has had the greatest global influence in improving clinical outcomes overall. Although the first-line metastatic breast cancer (MBC) trials comparing a third-generation aromatase inhibitor (AI) to tamoxifen have favored the AI, one of the challenges in translating these findings into clinical practice stems from the influence of prior adjuvant endocrine therapy, particularly the increasing use of adjuvant AIs today, on the choice of endocrine agent in the advanced setting because of the development of acquired resistance. Because the majority of patients enrolled into these studies were either endocrine-treatment naïve or exposed to tamoxifen only, the “real-life” applicability of the evidence is unclear. Because a superior dose of the selective estrogen receptor (ER) downregulator fulvestrant has now been established, its role as first-line therapy is being re-established. We are now starting to see the promise realized with blocking cross-talking growth factor pathways in addition to the ER pathway. The greatest efficacy is seen with the mammalian target of rapamycin (mTOR) inhibitor everolimus in combination with exemestane and, perhaps to a lesser extent, anti-HER2–directed therapy in combination with an AI. Future gains will likely involve a greater understanding of the redundancy and compensation induced by blocking these pathways, trials involving blocking multiple pathways in addition to hormonal agents, and the molecular interrogation of the individual's tumor in search of predictive biomarkers and “actionable” genomic aberrations.


2021 ◽  
Vol 28 (3) ◽  
pp. 1803-1822
Author(s):  
Samitha Andrahennadi ◽  
Amer Sami ◽  
Mita Manna ◽  
Mehrnoosh Pauls ◽  
Shahid Ahmed

Background: Hormone receptor-positive and HER2-negative breast cancer (HR + BC) is the most prevalent breast cancer. Endocrine therapy is the mainstay of treatment, however, due to the heterogeneous nature of the disease, resistance to endocrine therapy is not uncommon. Over the past decades, the emergence of novel targeted therapy in combination with endocrine therapy has shown improvement in outcomes of HR + BC. This paper reviews available data of targeted therapy and the results of pivotal clinical trials in the management of HR + BC. Methods: A literature search in PubMed and Google Scholar was performed using keywords related to HR + BC and targeted therapy. Major relevant studies that were presented in international cancer research conferences were also included. Results: Endocrine therapy with tamoxifen and aromatase inhibitors are backbone treatments for women with early-stage HR + BC leading to a significant reduction in mortality. They can also be used for primary prevention in women with a high risk of breast cancer. Preliminary data has shown the efficacy of adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitor, abemaciclib, in high-risk disease in combination with aromatase inhibitors. For most women with advanced HR + BC, endocrine therapy is the primary treatment. Recent evidence has shown that the use of CKD 4/6 inhibitors, mTOR inhibitors, and PI3K inhibitors in combination with endocrine therapy has been associated with better outcomes and delays initiation of chemotherapy. Several novel agents are under study for HR + BC. Discussion: Targeted treatment options for HR + BC have evolved. The future of overcoming resistance to targeted therapy, novel compounds, and predictive markers are key to improving HR + BC outcomes.


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