scholarly journals Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases

2021 ◽  
Author(s):  
Wing-Hong Jonathan Ho ◽  
Andrew M. K. Law ◽  
Etienne Masle-Farquhar ◽  
Lesley E. Castillo ◽  
Amanda Mawson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Cancer ◽  
Interferon Response ◽  
Breast Cancers ◽  
Oligoadenylate Synthetase ◽  
Cancer Metastases ◽  
Kaplan Meier ◽  
Programmed Death ◽  
Activating Mutation ◽  
Metastatic Activity

Abstract BackgroundThe interferon response can influence the primary and metastatic activity of breast cancers and can interact with checkpoint immunotherapy to modulate its effects. Using N-ethyl-N-nitrosourea mutagenesis we found a mouse with an activating mutation in oligoadenylate synthetase 2 ( Oas2 ), a sensor of viral double stranded RNA, that resulted in an interferon response and prevented lactation in otherwise healthy mice. MethodsTo determine if activation of Oas2 could alter the course of mammary cancer we combined the Oas2 mutation with the MMTV-PyMT oncogene model of breast cancer and examined disease progression and the effects of checkpoint immunotherapy using Kaplan-Meier survival analysis with immunohistochemistry and flow cytometry. ResultsOas2 mutation prevented pregnancy from increasing metastases to lung. Checkpoint immunotherapy with antibodies against programmed death-ligand 1 (PD-L1) was more effective when the Oas2 mutation was present. ConclusionsThese data establish OAS2 as a therapeutic target for agents designed to reduce metastases and increase the effectiveness of checkpoint immunotherapy in cases of pregnancy-associated breast cancer and outside of pregnancy in cases showing the lactation and involution-mimicry phenotypes.

scholarly journals Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 636 ◽  
Author(s):  
Regina Padmanabhan ◽  
Hadeel Shafeeq Kheraldine ◽  
Nader Meskin ◽  
Semir Vranic ◽  
Ala-Eddin Al Moustafa
Keyword(s):  
Breast Cancer ◽  
Mathematical Models ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Breast Cancers ◽  
Treatment Protocols ◽  
Cancer Subtypes ◽  
Cancer Management ◽  
Her2 Breast Cancer ◽  
Programmed Death

Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2+) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2+ breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2+ breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2+ breast cancer management, we also review mathematical models pertaining to the dynamics of HER2+ breast cancer and immune checkpoint inhibitors.

scholarly journals Performing Data Mining to Explain the Correlation between the BIRC5 Gene and Prognosis in Breast Cancer Patients

2020 ◽  
Author(s):  
Hong Dongsheng ◽  
Zhang YanFang ◽  
Ye Ziqi ◽  
Chen Jing ◽  
Lu Xiaoyang
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Cancer Cell Line ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Kaplan Meier ◽  
Er Positive

Abstract Background: Breast cancer is the most commonly malignant cancers in women, and BIRC5 has been found to be overexpressed in a variety of human tumors. Its expression is associated with the prognosis of many cancers. However, whether BIRC5 mRNA could be used as an independent prognostic factor for breast cancer remains inconsistent in previous studies.Methods: Altered BIRC5 expression in normal tissue relative to various tumor tissue and in breast cancer patients with different molecular subtypes, clinical outcomes and chemotherapy responses were examined using the Oncomine, GOBO and Kaplan-Meier plotter datasets.Results: We found that many breast cancers had increased BIRC5 mRNA expression, and GOBO analysis showed that triple-negative cell lines displayed highest BIRC5 mRNA expression levels in the breast cancer cell line panel. Moreover, BIRC5 high mRNA expression was significantly associated with longer relapse-free survival (RFS) in all breast cancer patients. In particular, sub analysis revealed that high mRNA expression of BIRC5 was significantly associated with better survival in ER positive (HR = 2.05, p = 1e-16), but not in ER negative breast cancer (HR = 1.24, p = 0.1), furthermore, the results also demonstrated that BIRC5 high expression was significantly associated with longer RFS in luminal A (HR = 1.51, p = 3.1e-06) and luminal B (HR = 1.28, p = 0.026).Conclusions: In conclusion, BIRC5 is involved in the development and progression of breast cancer and may be a suitable prognostic marker for human breast cancer.

Interferon in Breast Cancer

1977 ◽  
Vol 63 (2) ◽  
pp. 155-162 ◽  
Author(s):  
Eugenia S. De Lustig ◽  
Nuria Cortada De De La Peña ◽  
Abel Canonico
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Mammary Cancer ◽  
Inverse Correlation ◽  
Interferon Response ◽  
Normal Donor ◽  
Interferon Production ◽  
Human Breast ◽  
Remission Period

The interferon production ability by leukocytes in vitro from 37 patients with mammary cancer was studied. The leukocytes were derived from patients between 27 and 80 years of age, 6 months and up to 28 years after removal of the primary tumor. The interferon titer of 34/37 human breast cancer leukocytes was 2–8 times lower than that of 35 normal donor leukocytes and 3 non-neoplastic diseases. No correlation between interferon titers, the patient's age, and the histologic tumor features was observed; however, interferon production was observed to return to normal in those patients who had a long remission period or whose tumors were locally confined. Interferon response of patients under different therapy was modified: radiotherapy affected interferon production more severely than chemotherapy. A tendency for association between the skin DNCB test and interferon response was found. An inverse correlation was observed between interferon titers and the PHA-induced transformation index.

scholarly journals Methylated PLK2 is a prognostic biomarker in taxane-treated breast cancers

2020 ◽  
Vol 7 (2) ◽  
pp. 7
Author(s):  
Priti Chivers ◽  
Laura Lattanzio ◽  
Ornella Garrone ◽  
Daniela Vivenza ◽  
Nel Syed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Promoter Methylation ◽  
Cpg Island ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Breast Cancers ◽  
Kaplan Meier ◽  
Treated Breast ◽  
Neo Adjuvant Chemotherapy ◽  
Drug Responsiveness

Background: In search of potential biomarkers of drug responsiveness the tumour suppressor PLK2 has been identified as a mediator of taxane sensitivity in some tumour types, based on its role of G2M checkpoint regulation.Objective: The current study set out to evaluate PLK2 methylation in breast cancer treated with neo-adjuvant chemotherapy including a taxane, as a biomarker of disease progression.Methods: Silencing of PLK2 in MCF-7 cells followed by taxane treatment was assessed using apoptotic readout for proof of principle. DNA was extracted from 64 cases of diagnostic surgical FFPE sections. Using pyrosequencing, levels of PLK2 promoter methylation were measured.Results: Silencing of PLK2 resulted in a significantly reduced apoptotic response following paclitaxel treatment (compared with scramble transfected controls). An association with higher levels of CpG island promoter methylation was seen for those cases with a progression-free survival (PFS) of less than 12 months. Kaplan-Meier analysis showed there was an association between overall survival (OS) and level of methylation (p = .06).Conclusions: Thus, based on data obtained from this pilot study, further larger studies evaluating the utility of PLK2 methylation as a potential predictive biomarker in breast cancer are warranted.

Increased favorability of small breast cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12576-e12576
Author(s):  
Shigeto Maeda ◽  
Kosho Yamanouchi ◽  
Takanori Hirayama ◽  
Shinichiro Kobayashi ◽  
Hiroyuki Tokunag ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Medical Center ◽  
The Other ◽  
Stage I ◽  
Biological Behavior ◽  
Breast Cancers ◽  
Hospital Organization ◽  
Kaplan Meier ◽  
Small Breast ◽  
Magnetic Resonance Imaging Mri

e12576 Background: Breast cancer is classified into three prognostic groups based on the following biologic factors: estrogen-receptor (ER) status, progesterone-receptor (PR) status, and nuclear grade (NG). According to this classification, we determined the biological behavior in order to understand if a small breast cancer is biologically more favorable than a large one (T1-2 breast cancers). Methods: The inclusion criteria for this study were (1) presence of T1-2 breast cancer measurable by magnetic resonance imaging (MRI) or ultrasound(US), and (2) availability for determination of ER, PR, and NG histological status. Inflammatory breast cancer, male breast cancer, tumors of unknown size on MRI or US, and complications due to other cancers were excluded from this study. From April 2007 to December 2019, 1173 patients with surgically proven breast cancer presented at National Hospital Organization Nagasaki Medical Center, and 1080 patients were retrospectively analyzed. The favorable (F), intermediate (I), and unfavorable (UF) groups were defined as follows. F: NG1 (ER+PR+, ER+PR-, ER-PR+), UF: NG2 (ER-PR-) or NG3 (ER-PR-, ER+PR-, ER-PR+). IF: all other types of F and UF. Overall survival (OS) was calculated using the Kaplan-Meier method. All statistical analyses were performed using JMP 9.0.2, and probability values of <0.05 were considered statistically significant. Results: Number (%), age (year), size (cm), and 10-year OS (%) in the F, I, and UF groups are presented in the table. The tumor size in F group was significantly smaller than that in the other groups and had better prognoses. The F, I, and UF distribution of tumors less than 1 cm in size were 66%, 29%, and 5%, respectively. On the other hand, the F, I, and UF distribution of tumors 1-2 cm, 2-3 cm, 3-4 cm, 4-5 cm in sizes were (42%, 41%, 17%), (34%, 46%, 20%), (31%, 39%, 30%), and (27%, 45%, 28%), respectively. The 10-year OS of F group stage I, I group stage I, F group stage II, and UF group stage I were 99%, 94%, 93%, and 80%, respectively. Conclusions: Small breast cancers, especially those less than 1 cm in size, were shown to be significantly biologically favorable. Small breast cancers are candidates for de-escalation of treatment. [Table: see text]

scholarly journals The Prognosis of Single Hormone Receptor-Positive Breast Cancer Stratified by HER2 Status

2021 ◽  
Vol 11 ◽  
Author(s):  
Hengqiang Zhao ◽  
Yiping Gong
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Total Population ◽  
Molecular Subtypes ◽  
Her2 Status ◽  
Breast Cancers ◽  
Cancer Specific Survival ◽  
Hormone Receptor Positive ◽  
Kaplan Meier ◽  
Positive Breast Cancer

Single estrogen receptor (ER)+ and progesterone receptor (PR)+ tumors account for about10% of all breast cancers. However, the prognosis of these single hormone receptor-positive (HR+) tumor remains unclear. We aimed to investigate the characteristics of single HR+ breast tumors according to HER2 status in order to improve the treatment of patients with single HR+. Patients from the SEER program (2010-2016) were divided into ER+PR-, ER-PR+, ER+PR+ and ER-PR- molecular subtypes stratified by HER2 status. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared by Kaplan–Meier curves after propensity score matching (PSM). A total of 203,406 patients were enrolled. Single ER+ and PR+ tumors account for 11.9% of the total population. For HER2- subtype, patients with ER+PR- (n = 16906 pairs) and ER-PR+ (n = 1395 pairs) had worse prognoses than those with ER+PR+ with hazard ratio (HR) and 95% confidence interval (CI) of 1.52 (1.41-1.64) and 2.25 (1.76-2.88) for OS; and 1.94 (1.76-2.14) and 2.57 (1.94-3.40) for BCSS, respectively; ER+PR- showed a better prognosis than ER-PR+ (n = 1394 pairs) and ER-PR- (n = 9626 pairs) with HR (95% CI) of 1.32 (1.06-1.65) and 1.44 (1.33-1.55) for OS, and 1.32 (1.03-1.69) and 1.46 (1.34-1.60) for BCSS, respectively; ER-PR+ had a similar prognosis relative to ER-PR- (n = 1395 pairs) after PSM. For HER2+ subtype, patients with ER-PR+, ER+PR-, and ER-PR- had similar OS and BCSS; ER+PR+ showed a similar prognosis compare with ER-PR+ (n = 535 pairs), but had better OS and BCSS than ER+PR- (n = 5376 pairs) and ER-PR- (n = 8143 pairs) after PSM. In addition, ER+PR+HER2+ showed similar OS and better BCSS compared with ER+PR+HER2- after PSM. In conclusion, single PR+ patients experienced poorer prognoses than single ER+ patients, and may be treated as ER-PR- patients in HER2- subtype. In HER2+ patients, both single ER+ and single PR+ cases showed similar prognoses compared with ER-PR- cases, and may be treated as ER-PR- patients.

scholarly journals Clinical significance of extranodal extension in sentinel lymph node positive breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xia Yang ◽  
XiaoXi Ma ◽  
Wentao Yang ◽  
Ruohong Shui
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Lymph Node ◽  
Cox Regression ◽  
Rank Test ◽  
Breast Cancers ◽  
Cox Regression Analysis ◽  
Extranodal Extension ◽  
Kaplan Meier ◽  
Nodal Burden

Abstract The precise stage of lymph node (LN) metastasis is a strong prognostic factor in breast cancers, and sentinel lymph node (SLN) is the first station of nodal metastasis. A number of patients have extranodal extension (ENE) in SLN, whereas the clinical values of ENE in SLN in breast cancers are still in exploration. The aim of our study was to evaluate the predictive and prognostic values of ENE in SLN in breast cancers, and to investigate the feasibility of ENE to predict non-SLN metastasis, nodal burden, disease free survival (DFS) and overall survival (OS) in clinical practice. 266 cases of primary invasive breast cancer (cT1-2N0 breast cancer) underwent SLN biopsy and axillary lymph node dissection (ALND) between 2008 and 2015 were extracted from the pathology database of Fudan University Shanghai Cancer Center. ENE in SLN was defined as extension of neoplastic cells through the lymph-nodal capsule into the peri-nodal adipose tissue, and was classified as no larger than 2 mm and larger than 2 mm group. The associations between ENE and clinicopathological features, non-SLN metastasis, nodal burden, DFS, and OS were analyzed. In the 266 patients with involved SLN, 100(37.6%) were positive for ENE in SLN. 67 (25.2%) cases had ENE no larger than 2 mm in diameter, and 33(12.4%) had ENE larger than 2 mm. Among the clinicopathological characteristics, the presence of ENE in SLN was associated with higher pT and pN stages, PR status, lympho-vascular invasion. Logistic regression analysis indicated that patients with ENE in SLN had higher rate of non-SLN metastasis (OR4.80, 95% CI 2.47–9.34, P < 0.001). Meanwhile, in patients with SLN micrometastasis or 1–2 SLNs involvement, ENE positive patients had higher rate of non-SLN metastasis, comparing with ENE negative patients (P < 0.001, P = 0.004 respectively). The presence of ENE in SLN was correlated with nodal burden, including the pattern and number of involved SLN (P < 0.001, P < 0.001 respectively), the number of involved non-SLN and total positive LNs (P < 0.001, P < 0.001 respectively). Patients with ENE had significantly higher frequency of pN2 disease (P < 0.001). For the disease recurrence and survival status, Cox regression analysis showed that patients with ENE in SLN had significantly reduced DFS (HR 3.05, 95%CI 1.13–10.48, P = 0.008) and OS (HR 3.34, 95%CI 0.74–14.52, P = 0.092) in multivariate analysis. Kaplan–Meier curves and log-rank test showed that patients with ENE in SLN had lower DFS and OS (for DFS: P < 0.001; and for OS: P < 0.001 respectively). Whereas no significant difference was found in nodal burden between ENE ≤ 2 mm and > 2 mm groups, except the number of SLN metastasis was higher in patients with ENE > 2 mm. Cox regression analysis, Kaplan–Meier curves and log-rank test indicated that the size of ENE was not an independent factor of DFS and OS. Our study indicated that ENE in SLN was a predictor for non-SLN metastasis, nodal burden and prognosis in breast cancers. Patients with ENE in SLN had a higher rate of non-SLN metastasis, higher frequency of pN2 disease, and poorer prognosis. Patients with ENE in SLN may benefit from additional ALND, even in SLN micrometastasis or 1–2 SLNs involvement patients. The presence of ENE in SLN should be evaluated in clinical practice. Size of ENE which was classified by a 2 mm cutoff value had no significant predictive and prognostic values in this study. The cutoff values of ENE in SLN need further investigation.

scholarly journals Inflammatory Breast Cancer from Metastatic Ovarian Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-3 ◽  
Author(s):  
Vuthinun Achariyapota ◽  
Tuenjai Chuangsuwanich ◽  
Mongkol Benjapibal
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Inflammatory Breast Cancer ◽  
Clinical Importance ◽  
Advanced Ovarian Cancer ◽  
Metastatic Breast ◽  
Breast Cancers ◽  
Primary Ovarian Cancer ◽  
Cancer Metastases ◽  
Malignant Breast

Metastases to the breast from tumors other than breast carcinomas are extremely rare and represent only 0.2–1.3% of all diagnosed malignant breast tumors. Furthermore, while the most common sites for advanced ovarian cancer metastases are the liver, lung, and pleura, metastasis to the breast from a primary ovarian cancer is uncommon and has only been reported in 0.03–0.6% of all breast cancers. Here we describe a case report of a 50-year-old female patient with a rare case of breast metastases from an advanced ovarian cancer, presenting as inflammatory breast cancer. Our observations emphasize the clinical importance of distinguishing between primary and metastatic breast cancer during diagnosis for the purpose of appropriate prognosis and treatment.

scholarly journals Principles governing A-to-I RNA editing in the breast cancer transcriptome

2014 ◽  
Author(s):  
Debora Fumagalli ◽  
David Gacquer ◽  
Françoise Rothé ◽  
Anne Lefort ◽  
Frederick Libert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rna Editing ◽  
Cell Lines ◽  
Normal Breast ◽  
The Cancer Genome Atlas ◽  
Interferon Response ◽  
Breast Cancer Cell Lines ◽  
Type I ◽  
Breast Cancers ◽  
Cancer Transcriptome

A-to-I editing substitutes inosines for adenosines at specific positions in mRNAs and can substantially alter a cell's transcriptome. Currently, little is known about how RNA editing operates in cancer. Transcriptome analysis of 68 normal and cancerous breast tissues revealed that the editing enzyme ADAR acts uniformly, on the same loci, across tissues. Controlled ADAR expression experiments demonstrated that the editing frequency at all loci is proportional to both ADAR expression levels and the individual locus' editability?a propensity to be edited determined by the surrounding nucleotide sequence. Comparison of tumor transcriptomes to those of normal breast and breast organoids, i.e. pure normal breast epithelial cells, demonstrated that the editing frequency is increased in tumor cells. This was consistent with ADAR immunohistochemistry. We also demonstrated that type I interferon response and ADAR DNA copy number explain together 53% of ADAR expression in breast cancers, an observation also valid in nearly all of 20 other cancer types in The Cancer Genome Atlas. Interferon exposure increased ADAR mRNA, protein expression and editing in four breast cell lines. Finally, ADAR silencing using shRNA lentivirus transduction in breast cancer cell lines led to more cell proliferation and less apoptosis. Our results reveal that A-to-I editing is a pervasive, yet reproducible, source of variation that is controlled by two factors, 1q amplification and inflammation, both highly prevalent among human cancers. This suggests the potential for a new class of therapeutic targets and an unexpected role for inflammation in cancers.

Overexpressed FAM166B Predicts Favorable Prognosis and Associated With Metabolic Pathways and Tumor Immune Infiltrates in BRCA

2021 ◽  
Author(s):  
Yi Zhou ◽  
Huiqin Zhu ◽  
Gao He ◽  
Hongfei Zhang ◽  
Xuyu Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Immune Therapy ◽  
High Expression ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Protein Coding ◽  
Kaplan Meier ◽  
Cox Analysis

Abstract Background: Breast cancer is one of the most common and lethal cancer worldwide. Though surgery, chemotherapy, endocrine therapy and immune therapy have boost patients' survival rate, to establish more molecular biomarkers that can detect the early metastasis and shed a light on breast cancer treatment still requires efforts. Based on previous studies, adipose tissue had a metabolic crosstalk in breast cancer. FAM166B is a protein-coding gene which was reported to be found in adipose tissues. Yet whether FAM166B has a role in breast cancer had not been determined.Methods: In this study, 1109 BRCA patients and 113 adjacent cancer samples and clinical characteristics data were downloaded from TCGA data portal, R software and Strawberry Perl were used for all pre-processing processes. Kaplan-Meier plotter, univariate and multivariate Cox analysis were used to investigate FAM166B potential in BRCA prognosis. GSEA was performed to investigate the biological function of FAM166B. Furthermore, TIMER was utilized to identify the association between FAM166B and tumor-infiltrating immune cells.Results: We found out increased FAM166B expression correlates with better prognosis in BRCA. By conducting Multivariate Cox analysis, we draw a conclusion that FAM166B could be an independent prognosis factor. Moreover, the GSEA revealed that FAM166B could possibly restrain the cell metabolism and glucose converting pathways. Also, a high expression of FAM166B was correlated with increased immune infiltration levels like CD4+ T cells and decreased macrophages, especially in luminal and basal breast cancers. Conclusion: Our study illustrated that FAM166B is an independent prognostic factor in BRCA. A high expression of FAM166B indicates a better prognosis of breast cancer patients and it may restrain the tumor cell metabolism and likely play a role in immune cell infiltration.

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