Regulation of Immunity in Breast Cancer

Breast cancer affects millions of women worldwide, leading to many deaths and significant economic burden. Although there are numerous treatment options available, the huge potentials of immunotherapy in the management of localized and metastatic breast cancer is currently being explored. However, there are significant gaps in understanding the complex interactions between the immune system and breast cancer. The immune system can be pro-tumorigenic and anti-tumorigenic depending on the cells involved and the conditions of the tumor microenvironment. In this review, we discuss current knowledge of breast cancer, including treatment options. We also give a brief overview of the immune system and comprehensively highlight the roles of different cells of the immune system in breast tumorigenesis, including recent research discoveries. Lastly, we discuss some immunotherapeutic strategies for the management of breast cancer.

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Exosomal MicroRNAs and Organotropism in Breast Cancer Metastasis

Cancers ◽

10.3390/cancers12071827 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1827 ◽

Cited By ~ 2

Author(s):

Grace L. Wong ◽

Sara Abu Jalboush ◽

Hui-Wen Lo

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Tumor Microenvironment ◽

Cancer Metastasis ◽

Current Knowledge ◽

Metastatic Breast ◽

Tumor Stroma ◽

Breast Cancer Metastasis ◽

Exosomal Mirnas ◽

Made In

Breast cancer is the most frequent malignancy for women in which one in eight women will be diagnosed with the disease in their lifetime. Despite advances made in treating primary breast cancer, there is still no effective treatment for metastatic breast cancer. Consequently, metastatic breast cancer is responsible for 90% of breast cancer-related deaths while only accounting for approximately one third of all breast cancer cases. To help develop effective treatments for metastatic breast cancer, it is important to gain a deeper understanding of the mechanisms by which breast cancer metastasizes, particularly, those underlying organotropism towards brain, bone, and lungs. In this review, we will primarily focus on the roles that circulating exosomal microRNAs (miRNAs) play in organotropism of breast cancer metastasis. Exosomes are extracellular vesicles that play critical roles in intercellular communication. MicroRNAs can be encapsulated in exosomes; cargo-loaded exosomes can be secreted by tumor cells into the tumor microenvironment to facilitate tumor–stroma interactions or released to circulation to prime distant organs for subsequent metastasis. Here, we will summarize our current knowledge on the biogenesis of exosomes and miRNAs, mechanisms of cargo sorting into exosomes, the exosomal miRNAs implicated in breast cancer metastasis, and therapeutic exosomal miRNAs.

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Exploring Unmet Needs from an Online Metastatic Breast Cancer Support Group: A Qualitative Study

Medicina ◽

10.3390/medicina57070693 ◽

2021 ◽

Vol 57 (7) ◽

pp. 693

Author(s):

Aravinthan Kadravello ◽

Seng-Beng Tan ◽

Gwo-Fuang Ho ◽

Ranjit Kaur ◽

Cheng-Har Yip

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Support Group ◽

Unmet Needs ◽

Treatment Options ◽

Metastatic Breast ◽

Public Hospitals ◽

Online Support ◽

Online Support Group ◽

The Public

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.

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Treatment Options in Anthracycline and/or Taxane Pretreated Patients with Metastatic Breast Cancer

Onkologie ◽

10.1159/000342209 ◽

2012 ◽

Vol 35 (9) ◽

pp. 476-478

Author(s):

Lina Pugliano ◽

Evandro de Azambuja

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Treatment Options ◽

Metastatic Breast ◽

Pretreated Patients

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Effect and Safety of Anti-PD-1/PD-L1 Monotherapy for Metastatic Breast Cancer: A meta-analysis

10.21203/rs.2.12425/v1 ◽

2019 ◽

Author(s):

Yihang Qi ◽

Xiangyi Kong ◽

Xiangyu Wang ◽

Jie Zhai ◽

Yi Fang ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Survival Rate ◽

Response Rate ◽

Meta Analysis ◽

Treatment Options ◽

Metastatic Breast ◽

Clinical Activity ◽

Breast Cancer Patients ◽

Severe Grade

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.

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cPLA2 Blockade Attenuates S100A7-Mediated Breast Tumorigenicity by Inhibiting the Immunosuppressive Tumor Microenvironment

10.21203/rs.3.rs-829313/v1 ◽

2021 ◽

Author(s):

SANJAY MISHRA ◽

Manish Charan ◽

Rajni Kant Shukla ◽

Pranay Agarwal ◽

Swati Misri ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Tumor Microenvironment ◽

Tumor Growth ◽

Breast Cancer Cells ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Immunosuppressive Tumor Microenvironment ◽

Tumor Growth And Metastasis ◽

Breast Cancer Growth

Abstract Background: Metastasis is the major cause of mortality in breast cancer; however, the molecular mechanisms remain elusive. In our previous study, we demonstrated that S100A7/RAGE mediates breast cancer growth and metastasis by recruitment of tumor-associated macrophages. However, the downstream S100A7-mediated inflammatory oncogenic signaling cascade that enhances breast tumor growth and metastasis by generating the immunosuppressive tumor microenvironment (iTME) has not been studied. In this present study, we aimed to investigate the S100A7 and cPLA2 cross-talk in enhancing tumor growth and metastasis through enhancing the iTME.Methods: Human breast cancer tissue and plasma samples were used to analyze the expression of S100A7, cPLA2, and PGE2 titer. S100A7-overexpressing or downregulated human metastatic breast cancer cells were used to evaluate the S100A7-mediated downstream signaling mechanisms. Bi-transgenic mS100a7a15 overexpression, TNBC C3(1)/Tag transgenic, and humanized patient-derived xenograft mouse models and cPLA2 inhibitor (AACOCF3) were used to investigate the role of S100A7/cPLA2/PGE2 signaling in tumor growth and metastasis. Additionally, CODEX, a highly advanced multiplexed imaging was employed to delineate the effect of S100A7/cPLA2 inhibition on the recruitment of various immune cells.Results: S100A7 and cPLA2 are highly expressed and positively correlated in malignant breast cancer patients. S100A7/RAGE upregulates cPLA2/PGE2 axis in aggressive breast cancer cells. Furthermore, S100A7 is positively correlated with PGE2 in breast cancer patients. Moreover, cPLA2 pharmacological inhibition suppressed S100A7-mediated tumor growth and metastasis in multiple pre-clinical models. Mechanistically, S100A7-mediated activation of cPLA2 enhances the recruitment of immunosuppressive myeloid cells by increasing PGE2 to fuel breast cancer growth and its secondary spread. We revealed that cPLA2 inhibitor mitigates S100A7-mediated breast tumorigenicity by suppressing the iTME. Furthermore, CODEX imaging data showed that cPLA2 inhibition increased the infiltration of CD4+/CD8+ T cells in the TME. Analysis of metastatic breast cancer samples revealed a positive correlation between S100A7/cPLA2 with CD163+ tumor-associated M2-macrophages.Conclusions: Our study shows that cross-talk between S100A7 and cPLA2 plays an important role in enhancing breast tumor growth and metastasis by generating an immunosuppressive tumor microenvironment and reducing infiltration of T cells. Furthermore, S100A7 could be used as a novel non-invasive prognostic marker and cPLA2 inhibitors as promising drugs against S100A7-overexpressing metastatic breast cancer.

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Should All Patients With HR-Positive HER2-Negative Metastatic Breast Cancer Receive CDK 4/6 Inhibitor As First-Line Based Therapy? A Network Meta-Analysis of Data from the PALOMA 2, MONALEESA 2, MONALEESA 7, MONARCH 3, FALCON, SWOG and FACT Trials

Cancers ◽

10.3390/cancers11111661 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1661 ◽

Cited By ~ 4

Author(s):

Valentina Rossi ◽

Paola Berchialla ◽

Diana Giannarelli ◽

Cecilia Nisticò ◽

Gianluigi Ferretti ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Soft Tissues ◽

Meta Analysis ◽

Treatment Options ◽

Indirect Comparison ◽

Metastatic Breast ◽

Line Treatment ◽

First Line ◽

First Line Treatment

Background: We aim to understand whether all patients with hormonal receptor (HR)-positive (+)/human epidermal growth factor receptor-2 (HER2)-negative (−) metastatic breast cancer (MBC) should receive cyclin D-dependent kinase (CDK) 4/6 inhibitor-based therapy as a first-line approach. Methods: A network meta-analysis (NMA) using the Bayesian hierarchical arm-based model, which provides the estimates for various effect sizes, were computed. Results: First-line treatment options in HR+/HER2− MBC, including CDK 4/6 inhibitors combined with aromatase inhibitors (AIs) or fulvestrant (F), showed a significantly longer progression-free survival (PFS) in comparison with AI monotherapy, with a total of 26% progression risk reduction. In the indirect comparison across the three classes of CDK 4/6 inhibitors and F endocrine-based therapies, the first strategy resulted in longer PFS, regardless of specific CDK 4/6 inhibitor (HR: 0.68; 95% CrI: 0.53–0.87 for palbociclib + AI, HR: 0.65; 95% CrI: 0.53–0.79 for ribociclib + AI, HR: 0.63; 95% CrI: 0.47–0.86 for abemaciclib + AI) and patient’s characteristics. Longer PFS was also found in patients with bone-only and soft tissues limited disease treated with CDK 4/6 inhibitors. Conclusions: CDK 4/6 inhibitors have similar efficacy when associated with an AI in the first-line treatment of HR+ MBC, and are superior to either F or AI monotherapy, regardless of any other patients or tumor characteristics.

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