scholarly journals PTH1R-CaSR Cross Talk: New Treatment Options for Breast Cancer Osteolytic Bone Metastases

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yanmei Yang ◽  
Bin Wang

Metastatic breast cancer (BrCa) is currently incurable despite great improvements in treatment of primary BrCa. The incidence of skeletal metastases in advanced BrCa occurs up to 70%. Recent findings have established that the distribution of BrCa metastases to the skeleton is not a random process but due to the favorable microenvironment for tumor invasion and growth. The complex interplay among BrCa cells, stromal/osteoblastic cells, and osteoclasts in the osseous microenvironment creates a bone-tumor vicious cycle (a feed-forward loop) that results in excessive bone destruction and progressive tumor growth. Both the type 1 PTH receptor (PTH1R) and extracellular calcium-sensing receptor (CaSR) participate in the vicious cycle and influence the skeletal metastatic niche. Thus, this review focuses on how the PTH1R and CaSR signaling pathways interact and contribute to the pathogenesis of BrCa bone metastases. The effects of intermittent PTH and allosteric modulators of CaSR for the use of bone-anabolic agents and prevention of BrCa bone metastases constitute a proof of principle for therapeutic consideration. Understanding the interplay between PTH1R and CaSR signaling in the development of BrCa bone metastases could lead to a novel therapeutic approach to control both osteolysis and tumor burden in the bone.

2002 ◽  
Vol 9 (6) ◽  
pp. 480-489 ◽  
Author(s):  
Catherine H. Van Poznak

Background Bone is the most common site of breast cancer metastases. Skeletal metastases may be associated with harmful and painful events such as fractures, spinal cord compression, and hypercalcemia. By inhibiting osteoclasts and bone resorption, bisphosphonates can interrupt the process of bone destruction and decrease the risk of skeletal complications. Methods A review of the literature was undertaken regarding the use of bisphosphonates in breast cancer management, with particular attention to prospective, randomized clinical trials that have influenced the treatment of bone metastases. Results Large prospective, randomized trials have demonstrated that bisphosphonates are effective in reducing skeletal-related complications from metastatic breast cancer. Conclusions For many patients with osseous lesions from breast cancer, bisphosphonate therapy is a useful intervention in managing their disease. Bisphosphonates are the treatment of choice for hypercalcemia of malignancy and bisphosphonates reduce the risk of pathologic fractures, spinal cord compromise, the need for radiation or surgery to bone, and bone pain.


2016 ◽  
Vol 10 ◽  
pp. BCBCR.S32783 ◽  
Author(s):  
Simon B. Zeichner ◽  
Hiromi Terawaki ◽  
Keerthi Gogineni

Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC) disease. Although there have been many new treatment options approved by the Food and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic breast cancer, relatively few new agents have been approved for patients with mTNBC. There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patient's treatment course. Select synergistic combinations can produce faster and more significant response rates compared with monotherapy and are typically used in the setting of visceral threat or symptomatic disease. Preclinical studies have implicated other possible targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing new chemotherapeutic strategies and agents, including targeted therapy and immunotherapy. In this review, we evaluate the standard systemic and future treatment options in mTNBC.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1377
Author(s):  
Konstantinos Venetis ◽  
Roberto Piciotti ◽  
Elham Sajjadi ◽  
Marco Invernizzi ◽  
Stefania Morganti ◽  
...  

Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient’s survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients’ survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic.


Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 693
Author(s):  
Aravinthan Kadravello ◽  
Seng-Beng Tan ◽  
Gwo-Fuang Ho ◽  
Ranjit Kaur ◽  
Cheng-Har Yip

Background and Objective: Despite the increasing treatment options for patients with metastatic breast cancer (MBC), unmet needs remain common, especially in low and middle-income countries where resources are limited and MBC patients face many challenges. They often join support groups to cope with their unmet needs. Currently, many MBC patients connect with each other via online support group in view of the constant availability of support and rapid information exchange. The objective of this study is to determine the unmet needs of women with MBC from an online support group. Material and Methods: Messages in an online support group of twenty-two MBC patients over a period of three years from August 2016 till August 2019 were thematically analyzed. Results: Three themes were generated, (1) unmet information needs (2) unmet financial needs (3) unmet support needs. Women needed information on side effects of treatment, new treatment options and availability of clinical trials. Although Malaysia has universal health care coverage, access to treatment remains a major challenge. When treatment was not available in the public hospitals, or waiting lists were too long, women were forced to seek treatment in private hospitals, incurring financial catastrophe. Insufficient private insurance and inadequate social security payments force many women to consider stopping treatment. Women felt that they were not getting support from their clinicians in the public sector, who were quick to stop active treatment and advise palliation. On the other hand, clinicians in the private sector advise expensive treatment beyond the financial capability of the patients. Women with families also face the challenge of managing their family and household in addition to coping with their illness. Conclusions: There is a need for healthcare professionals, policy makers, and civil society to better address the needs of MBC patients through patient-centered, multidisciplinary and multi-organizational collaboration.


2019 ◽  
Author(s):  
Yihang Qi ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
Jie Zhai ◽  
Yi Fang ◽  
...  

Abstract Background. Given that no approved targeted agents for metastatic triple-negative breast cancer (mTNBC) and no opportunity of surgery for metastatic breast cancer (MBC), new treatment options are urgently to be discovered. The anti-PD-1/PD-L1 immunotherapy may be effective, and what we should be aware of is the response rate and adverse events. Methods. The PUBMED, EMBASE, Cochrane and www.clinicaltrials.gov databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1; metastatic; breast cancer. R© package Meta was used to pool incidence. Results. Six studies including 586 advanced breast cancer patients treated with anti-PD-1/PD-L1 agents were included in this meta-analysis. The anti-PD-1/PD-L1 agents include pembrolizumab, atezolizumab and avelumab. Among these patients, CR was 1.26%, PR was 7.65%, ORR was 9.85% and DCR was 18.33%. We also found that the response rate was closely associated with the expression of PD-L1 biomarker (PD-L1+ vs PD-L1-): the CR was 2.71% vs 0.00%; the PR was 9.93% vs 2.69%; the ORR was 10.62% vs 3.07%; the DCR was 17.95% vs 4.71%. 1-year overall survival rate and 6-months progression-free survival rate were 43.34% and 17.24%. Respectively, the overall incidence of AEs was 64.18% in any grade and 12.94% in severe grade. The incidence of irAEs was 14.75%. Besides, the incidence of discontinue and death due to treatment-related AEs was about 3.06% and 0.31% respectively. When the detailed AEs were analyzed, most treatment-related AEs of any grade were arthraigia, asthenia, decreased appetite; most common treatment-related AEs of severe grade were anemia, autoimmune hepatitis, diarrhea; the most common irAEs were hypothyroidism , followed by hyperthyroidism, pneumonitis and infusion-related reaction. Conclusions. Anti-PD-1/PD-L1 monotherapy showed a manageable safety profile and had a durable anti-tumor clinical activity in a subset of patients with mTNBC or MBC. PD-L1 expression may be correlated to a higher probability of clinical response.


2021 ◽  
Vol 23 (1) ◽  
pp. 78-81
Author(s):  
Inna P. Ganshina ◽  
Olga O. Gordeeva ◽  
Mariam S. Manukyan

Metastatic triple negative breast cancer (mTNBC) is a difficult task for the chemotherapist in view of the disease aggressiveness, biological heterogeneity of the tumor, as well as the limit of therapy options. The approved modern drugs, such as immunotherapy and PARP inhibitors, have improved the treatment results in women with mTNBC. However, not all women are the candidates for this kind of therapy due to the lack of suitable points of application. In this context, high hopes are placed on the new treatment options currently being studied in clinical trials. The review summarizes data on advanced drugs that have demonstrated their efficacy in this multiplex group of women, but not yet registered at the territory of the Russian Federation Russian Federation, and will allow us to form an idea of the future algorithm of treatment of women with mTNBC.


Surgery ◽  
2013 ◽  
Vol 153 (6) ◽  
pp. 771-778 ◽  
Author(s):  
Omar M. Rashid ◽  
Masayuki Nagahashi ◽  
Subramaniam Ramachandran ◽  
Laura Graham ◽  
Akimitsu Yamada ◽  
...  

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