scholarly journals Moringa Oleifera Seed Extract Concomitantly Supplemented with Chemotherapy Worsens Tumor Progression in Mice with Triple Negative Breast Cancer and Obesity

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2923
Author(s):  
Elizabeth R. M. Zunica ◽  
Shengping Yang ◽  
Ann Coulter ◽  
Christy White ◽  
John P. Kirwan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Triple Negative Breast Cancer ◽  
Moringa Oleifera ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Metastatic Breast ◽  
Seed Extract ◽  
Edible Plant ◽  
Anti Cancer

Triple negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype with limited treatment options. Obesity and insulin resistance are associated with a worse prognosis in those with TNBC. Moringa oleifera (moringa) is a tropical edible plant used for both food and medicinal purposes and found to have anti-obesity and anti-cancer effects in vitro and in preclinical models. The anti-cancer effects of moringa seed extract alone and in combination with chemotherapy were evaluated in immunocompromised female mice with diet-induced obesity bearing MDA-MB-231-derived xenograft tumors. Moringa supplementation protected against high-fat diet- and chemotherapy-induced increases in fasting glucose and improved insulin sensitivity. Moringa supplementation alone did not attenuate tumor growth relative to chemotherapy alone, and in combination worsened tumor progression. Moringa supplementation alone reduced angiogenesis, but this effect was abrogated in combination with chemotherapy. Moringa supplementation may be an effective strategy to improve metabolic health in mice with obesity and TNBC and reduce angiogenesis in tumors, but may have a negative interaction when used as a concurrent complementary therapy. Caution should be taken when considering the consumption of moringa seed extracts while receiving chemotherapy for breast cancer treatment. Further investigations of alternative timings of moringa therapy are warranted.

Functional hotness score based on three genes predicts long-term survival of triple-negative breast cancer independent from tumor mutational burden.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12583-e12583
Author(s):  
Eriko Katsuta ◽  
Li Yan ◽  
Mateusz Opyrchal ◽  
Pawel Kalinski ◽  
Kazuaki Takabe
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Cancer Prognosis ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Expression Levels ◽  
Cancer Immunity ◽  
Anti Cancer

e12583 Background: Cytotoxic T-lymphocytes (CTLs) infiltration into tumor is a positive prognostic factor in breast cancer. Infiltration of CTLs are believed to be driven by mutation-induced neoantigens, thus, higher tumor mutation burden (TMB) is considered an important predictor of tumor immunogenicity and response to immunotherapy, but the association between intratumoral CTL counts and TMB in the overall cancer prognosis remains unclear. Methods: Utilizing publicly available breast cancer cohorts, we established Functional Hotness Score (FHS), based on CD8A, GZMB and CXCL10 gene expression levels of bulk tumors. The associations of FHS and breast cancer patient prognosis as well as distinct immunity markers were analyzed. Results: Breast cancer patients with high-FHS tumors demonstrated significantly better survival. FHS was lower in metastatic breast cancer. Among breast cancer subtypes, triple-negative breast cancer (TNBC) showed the highest FHS. FHS predicted patient survival not in hormone receptor (HR)-positive but in HR-negative, especially TNBCs. The high-FHS TNBCs enhanced not only CD8+ T cell infiltration, but also a broader type-1 anti-cancer immunity. The patients with the high-FHS patients showed better prognosis not only in high-TMB tumors but also in low-TMB TNBCs. The combination of high-TMB with high-FHS identified the unique subset of patients who did not recur over time. Conclusions: In conclusion, TNBCs with high-FHS based on the expression levels of CD8A, GZMB and CXCL10 showed improved prognosis with higher anti-cancer immunity regardless of TMB, and constituting an independent prognostic marker of survival, particularly robust when combined with TMB.

Tumor-infiltrating lymphocytes in androgen receptor-positive, triple-negative breast cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 5-5 ◽  
Author(s):  
Roberto Antonio Leon-Ferre ◽  
Mei-Yin Polley ◽  
Heshan Liu ◽  
Victoria Cafourek ◽  
Judy Caroline Boughey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Metastatic Breast ◽  
Tumor Infiltrating Lymphocytes ◽  
Surgical Specimen ◽  
Er Positive ◽  
Infiltrating Lymphocytes

5 Background: Triple-negative breast cancer (TNBC) is an immunogenic breast cancer subtype, with a greater percentage of tumors containing tumor-infiltrating lymphocytes (TILs) compared to non-TNBC. TILs are prognostic for recurrence and predictive for chemotherapy benefit in TNBC, but not in estrogen receptor (ER)-positive tumors. A subset of TNBC expresses the androgen receptor (AR), and resembles ER-positive breast cancer in terms of demographics (older age) and clinical course (later recurrences that tend to involve bone). However, little is known regarding the association between TILs and AR expression in TNBC. Methods: From a cohort of 9982 women with surgically-treated non-metastatic breast cancer, patients who met criteria for TNBC (ER/PR < 1% and HER2-negative) by centralized-pathology review were included as previously published [Leon-Ferre et al, Breast Cancer Res Treat 2017]. Stromal TILs in these tumors were quantified on full-face hematoxylin and eosin sections from the surgical specimen, following the 2014 TIL Working Group recommendations [Salgado et al, Ann Oncol 2014]. The expression of AR [EPR1535(2), Abcam] was scored as a continuous variable (1% increments), and categorized as absent (0%), low (1-25% ), low-moderate (26-50%) moderate (51-75%) and high (> 75%) and correlated with TIL density. Results: 605 patients met criteria for TNBC. The median age was 56 years. Most tumors were T1-2 (95%), N0-1 (86%), and high grade (88%). The median stromal TIL content was 20% (0-90%). Tumor tissue was available for AR staining in 509/605 patients. 165 (32%) tumors expressed AR as follows: low: 12%, low-moderate: 7%, moderate: 5%, and high: 8%. Apocrine tumors (n = 30) expressed AR most frequently (86%) and at higher levels (AR high: 50%). For all 509 tumors, the median stromal TIL content according to AR expression was AR absent: 20%, AR low: 20%, AR low-moderate: 15%, AR high: 10%. AR and stromal TILs (both as continuous variables) demonstrated a weak inverse correlation (correlation coefficient -0.1064, p = 0.017). Conclusions: AR expression in TNBC is associated with lower levels of stromal TILs. Additional data correlating the AR, stromal TILs and outcomes in this cohort will be presented at the meeting.

scholarly journals Novel antibody–drug conjugates for triple negative breast cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592091598 ◽  
Author(s):  
Aiko Nagayama ◽  
Neelima Vidula ◽  
Leif Ellisen ◽  
Aditya Bardia
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Clinical Development ◽  
Antibody Drug Conjugate ◽  
Drug Conjugates ◽  
Anti Cancer ◽  
Late Stages ◽  
Antibody Drug

Triple negative breast cancer (TNBC) is a heterogenous subtype of breast cancer often associated with an aggressive phenotype and poor prognosis. Antibody–drug conjugate (ADC), comprising of a monoclonal antibody linked to a cytotoxic payload by a linker, is gaining increasing traction as an anti-cancer therapeutic. Emerging ADC drugs such as sacituzumab govitecan (IMMU-132) and trastuzumab deruxtecan (DS-8201a) are in late stages of clinical development for patients with metastatic breast cancer, including TNBC. In this article, we review and discuss the development and clinical application of ADCs in patients with advanced TNBC.

scholarly journals RNF8–CDH1 Co-Expression Predicts Clinical Benefit of Chemoradiotherapy in Triple-Negative Breast Cancer

2021 ◽  
Vol 11 (7) ◽  
pp. 655
Author(s):  
Chieh-Ni Kao ◽  
Sin-Hua Moi ◽  
Ming-Feng Hou ◽  
Chi-Wen Luo ◽  
Fang-Ming Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Unmet Need ◽  
Ring Finger ◽  
High Index ◽  
Anti Cancer ◽  
Suitable Treatment

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and exhibits an overall poor outcome. Due to the lack of targeted therapy, conventional systemic chemotherapy has been the main strategy for the treatment of TNBC. Further evidence has shown that combining radiation with chemotherapy is also a suitable treatment based on DNA repair deficiencies in patients with TNBC. However, the preferred treatment for metastatic TNBC remains unclear. Therefore, identification of biomarkers is an unmet need in personalized therapy for TNBC. RNF8 (ring finger protein 8) is a ubiquitin ligase implicated in TNBC metastasis; however, its role in TNBC pathogenesis is unclear. The purpose of the present study was to investigate the roles of the RNF8–CDH1(Cadherin 1) axis in node-positive TNBC patients. We found that the RNF8high/CDH1low index was significantly higher in patients with TNBC than in patients without TNBC. Furthermore, patients with an RNF8high/CDH1low index displayed poorer outcomes than those with an RNF8low-medium/CDH1medium-high index. Notably, as compared to patients with an RNF8low-medium/CDH1medium-high index, those with an RNF8high/CDH1low index had a poorer survival rate with chemotherapy treatment alone. The combination of radiation and chemotherapy resulted in a better survival rate than chemotherapy alone in patients with an RNF8high/CDH1low index. Taken together, the RNF8high/CDH1low index not only functions as a prognostic and therapeutic marker but may also act as a target in the development of anti-cancer agents for patients with TNBC.

scholarly journals Selection of aptamers against triple negative breast cancer cells using high throughput sequencing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Débora Ferreira ◽  
Joaquim Barbosa ◽  
Diana A. Sousa ◽  
Cátia Silva ◽  
Luís D. R. Melo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Throughput ◽  
Triple Negative Breast Cancer ◽  
High Throughput Sequencing ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Target Cells ◽  
Cancer Tissue ◽  
Surface Receptors

AbstractTriple-negative breast cancer is the most aggressive subtype of invasive breast cancer with a poor prognosis and no approved targeted therapy. Hence, the identification of new and specific ligands is essential to develop novel targeted therapies. In this study, we aimed to identify new aptamers that bind to highly metastatic breast cancer MDA-MB-231 cells using the cell-SELEX technology aided by high throughput sequencing. After 8 cycles of selection, the aptamer pool was sequenced and the 25 most frequent sequences were aligned for homology within their variable core region, plotted according to their free energy and the key nucleotides possibly involved in the target binding site were analyzed. Two aptamer candidates, Apt1 and Apt2, binding specifically to the target cells with $$K_{d}$$ K d values of 44.3 ± 13.3 nM and 17.7 ± 2.7 nM, respectively, were further validated. The binding analysis clearly showed their specificity to MDA-MB-231 cells and suggested the targeting of cell surface receptors. Additionally, Apt2 revealed no toxicity in vitro and showed potential translational application due to its affinity to breast cancer tissue sections. Overall, the results suggest that Apt2 is a promising candidate to be used in triple-negative breast cancer treatment and/or diagnosis.

scholarly journals The extracellular-regulated protein kinase 5 (ERK5) enhances metastatic burden in triple-negative breast cancer through focal adhesion protein kinase (FAK)-mediated regulation of cell adhesion

Oncogene ◽  
2021 ◽  
Author(s):  
Qiuping Xu ◽  
Jingwei Zhang ◽  
Brian A. Telfer ◽  
Hao Zhang ◽  
Nisha Ali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Kinase ◽  
Tumor Growth ◽  
Focal Adhesion ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Adhesion Protein ◽  
Focal Adhesion Protein

AbstractThere is overwhelming clinical evidence that the extracellular-regulated protein kinase 5 (ERK5) is significantly dysregulated in human breast cancer. However, there is no definite understanding of the requirement of ERK5 in tumor growth and metastasis due to very limited characterization of the pathway in disease models. In this study, we report that a high level of ERK5 is a predictive marker of metastatic breast cancer. Mechanistically, our in vitro data revealed that ERK5 was critical for maintaining the invasive capability of triple-negative breast cancer (TNBC) cells through focal adhesion protein kinase (FAK) activation. Specifically, we found that phosphorylation of FAK at Tyr397 was controlled by a kinase-independent function of ERK5. Accordingly, silencing ERK5 in mammary tumor grafts impaired FAK phosphorylation at Tyr397 and suppressed TNBC cell metastasis to the lung without preventing tumor growth. Collectively, these results establish a functional relationship between ERK5 and FAK signaling in promoting malignancy. Thus, targeting the oncogenic ERK5-FAK axis represents a promising therapeutic strategy for breast cancer exhibiting aggressive clinical behavior.

Effectiveness of combination with eribulin in third line of chemotherapy for triple negative breast cancer (case report)

2021 ◽  
Vol 1 (31) ◽  
pp. 20-24
Author(s):  
M. V. Kalugin ◽  
K. A. Ivanova ◽  
E. I. Borisova ◽  
S. S. Nakhapetyan ◽  
S. L. Gutorov
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Breast Cancer Case ◽  
Cancer Case ◽  
Antitumor Action ◽  
Illustrative Case ◽  
Development Of Resistance ◽  
Triple Negative Phenotype

In most cases triple negative breast cancer is characterized by an aggressive course of disease and early development of resistance to chemotherapy. Thereafter, the late-line treatment choice, usually after anthracyclines and taxanes, is problematic due to the limited amount of effective and low-toxic cytostatics. In our opinion, in this situation the use of eribulin which possesses unique antitumor action mechanisms is a good option. An illustrative case of a pronounced antitumor effect of eribulin in metastatic breast cancer with triple negative phenotype resistant to previous lines of chemotherapy is presented.

scholarly journals How shall we treat locally advanced triple negative breast cancer?

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 1649
Author(s):  
Paulo Luz ◽  
David Dias ◽  
Ana Fortuna ◽  
Luis Bretes ◽  
Beatriz Gosalbez
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Surrogate Marker ◽  
Metastatic Breast ◽  
Complete Response ◽  
Number Of Patients ◽  
Her 2 ◽  
Near Future

Triple negative breast cancer (TNBC) has been shown to respond to neoadjuvant chemotherapy (NACT). It has been established that achieving pathological complete response (pCR) for certain aggressive subtypes of breast cancer, including HER-2 (over-expressed) and TNBC, provides an important surrogate marker for predicting long-term clinical response and survival outcomes. How to increase the number of patients that achieve pCR remains challenging. Platinum-based NACT seems to be part of the solution and capecitabine, an active drug in metastatic breast cancer, but not a standard one in earlier stages may have found its place in the adjuvant setting. In the near future immunotherapy can play a role in early TNBC

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