Association of cytoplasmic HMGB1 (cHMGB1) expression with local tumor recurrence in triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12595-e12595
Author(s):  
Iandra Freire Oliveira ◽  
Jhonata Lima Rocha ◽  
Anamaria Falcão Pereira ◽  
Marina Helena Silva Lopes ◽  
Aurilene Gomes Cajado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Tumor Recurrence ◽  
Triple Negative ◽  
Progesterone Receptors ◽  
High Mobility ◽  
Local Tumor ◽  
Local Tumor Recurrence ◽  
Risk Of Death ◽  
Hospital Ethics

e12595 Background: Breast cancer is one of the most frequent neoplasms worldwide, contributing to women's morbimortality. Triple-negative breast cancer (TNBC) is a highly aggressive subtype of cancer marked by negative estrogen receptors, progesterone receptors, and lack of the human epidermal growth factor 2 (C-erbB2, HER2/neu) gene overexpression. The high mobility group box-1 (HMGB1) is a factor that regulates malignant tumorigenesis, proliferation, and metastasis. Aim: Here, the HMGB1 expression was investigated as a prognostic factor for TNBC. Methods: Clinico-pathological data and surgical paraffin histopathology blocks were assessed from 85 patients treated at Haroldo Juaçaba Hospital (Ethics committee approval number 407.395). Samples were analyzed by immunofluorescence using the Tissue Microarray technique to determine the percentage of fluorescent cells with cytoplasmic HMGB1 (cHMGB1) expression. Results: The clinico-pathological data analysis indicated that patients were older than 50 years (68.2%) and diagnosed with grade 2–3 ductal carcinomas (91.8%). Tumor metastasis was observed in 9.9% of cases. TNBC patients that tumor cells presented high cHMGB1 fluorescence demonstrated increased local tumor recurrence compared with low expressing tumors (P=0.019). Five-year overall survival was simmilar between the patients with low (63%) versus high (66%) cHMGB1 expression (P=0.7441). Additionally, the risk of death was 0.8 (95% CI = 0.21–2.96). Conclusions: The cHMGB1 expression is associated with an increased tumor relapse in TNBC, not affecting patients' survival.

Cytoplasmic CCR7 (CCR7c) immunoexpression is associated with local tumor recurrence in triple-negative breast cancer

2020 ◽  
Vol 216 (12) ◽  
pp. 153265
Author(s):  
Daniel Cordeiro Gurgel ◽  
Deysi Viviana Tenazoa Wong ◽  
Alessandro Maia Bandeira ◽  
Jorge Fernando Bessa Pereira ◽  
Jedson Vieira Gomes-Filho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Tumor Recurrence ◽  
Triple Negative ◽  
Local Tumor ◽  
Local Tumor Recurrence

scholarly journals Triple-Negative Breast Cancer: Adjuvant Therapeutic Options

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Ayca Gucalp ◽  
Tiffany A. Traina
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Cytotoxic Chemotherapy ◽  
Breast Cancers ◽  
Targeted Agents ◽  
Increased Risk ◽  
Disproportionate Number

Triple-negative breast cancer (TNBC), a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2(HER2) represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents.

scholarly journals Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3357
Author(s):  
Hongmei Zheng ◽  
Sumit Siddharth ◽  
Sheetal Parida ◽  
Xinhong Wu ◽  
Dipali Sharma
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Combined Treatment ◽  
High Mobility ◽  
Sphingosine 1 Phosphate ◽  
Molecular Patterns

Triple negative breast cancer (TNBC) is a heterogeneous disease and is highly related to immunomodulation. As we know, the most effective approach to treat TNBC so far is still chemotherapy. Chemotherapy can induce immunogenic cell death, release of damage-associated molecular patterns (DAMPs), and tumor microenvironment (TME) remodeling; therefore, it will be interesting to investigate the relationship between chemotherapy-induced TME changes and TNBC immunomodulation. In this review, we focus on the immunosuppressive and immunoreactive role of TME in TNBC immunomodulation and the contribution of TME constituents to TNBC subtype classification. Further, we also discuss the role of chemotherapy-induced TME remodeling in modulating TNBC immune response and tumor progression with emphasis on DAMPs-associated molecules including high mobility group box1 (HMGB1), exosomes, and sphingosine-1-phosphate receptor 1 (S1PR1), which may provide us with new clues to explore effective combined treatment options for TNBC.

Retrospective Study about the Prevalence of (TILs) Tumor Infiltrating Lymphocytes in Non-Metastatic Triple Negative Breast Cancer Patients and its Prognostic Value

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Hesham Ahmed ElGhazaly ◽  
Manal Mohamed El-Mahdy ◽  
Azza Mohamed Adel ◽  
Nermeen Mostafa ◽  
Aya Magdy Kamal Ali
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Retrospective Study ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Free Survival ◽  
Female Patients ◽  
Risk Of Death ◽  
Reduced Risk

Abstract Background TNBC comprises a distinct disease entity with a unique microenvironment of TILs, the immunogenic potential of TNBC is derived from its genetic instability and high mutation rate. Tumors from patients with TNBC are more likely than tumors from patients with other subtypes to exhibit chromosomal instability and potential mutations. Objectives The study aims to evaluate the prevalence of CD8+ TILs biomarker by IHC in triple negative breast cancer and its prognostic value. TILs are an important prognostic value for the response of patient to chemotherapy the greater number of TILS is associated with higher probability of response to chemotherapy also decrease recurrence. TILS in triple negative breast cancer suggest a likely option for immunotherapy in this disease. Patients and Methods This is a retrospective study, which was carried on 30 female patients, Clinical data and paraffin wax block of female patients with triple negative breast cancer are to be collected from the breast cancer unit, department of clinical Oncology and Nuclear medicine Ain Shams university and Matarya teaching hospital. Results Several large systematic reviews and meta-analyses have confirmed that high levels of TILs are associated with better disease free survival and overall survival only in triple negative and HER2 positive subtypes, with no significant benefit seen in estrogen receptor positive breast carcinoma. In the Breast International Group (BIG) 02-98 trial shows that for every 10% increase in the intertumoral TILs there was a 17% reduced risk of relapse, and 27% reduced risk of death regardless of chemotherapy type. Also in eastern cooperative oncology group trial (ECOG) 2197, and 1199 showed that for every 10% increase in TILs, a 14% reduction of risk of recurrence, and 19% reduction in risk of death were observed. Conclusion Our study showed that All our patients (100%) were positive for CD8+, with a minimum range of 1% and a maximum range of 60%, most of the patients (20 patients) had CD8% between (10% to 20%). High levels of CD8 + TILs are good prognostic indicators in TNBC. our study showed that there were associations of CD8+ TILs infiltrate status with longer progression free survival and better overall survival in triple-negative breast cancer, but were not statistically significant probably due to our small sample size.

scholarly journals WDHD1 is essential for the survival of PTEN-inactive triple-negative breast cancer

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Ayse Ertay ◽  
Huiquan Liu ◽  
Dian Liu ◽  
Ping Peng ◽  
Charlotte Hill ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Synthetic Lethality ◽  
Essential Gene ◽  
Growth Factor Receptor ◽  
High Mobility ◽  
Protein Translation ◽  
Sirna Screen ◽  
Potential Biomarker

AbstractTriple-negative breast cancer (TNBC) is the most aggressive type of breast cancer that lacks the oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, making it difficult to target therapeutically. Targeting synthetic lethality is an alternative approach for cancer treatment. TNBC shows frequent loss of phosphatase and tensin homologue (PTEN) expression, which is associated with poor prognosis and treatment response. To identify PTEN synthetic lethal interactions, TCGA analysis coupled with a whole-genome siRNA screen in isogenic PTEN-negative and -positive cells were performed. Among the candidate genes essential for the survival of PTEN-inactive TNBC cells, WDHD1 (WD repeat and high-mobility group box DNA-binding protein 1) expression was increased in the low vs. high PTEN TNBC samples. It was also the top hit in the siRNA screen and its knockdown significantly inhibited cell viability in PTEN-negative cells, which was further validated in 2D and 3D cultures. Mechanistically, WDHD1 is important to mediate a high demand of protein translation in PTEN-inactive TNBC. Finally, the importance of WDHD1 in TNBC was confirmed in patient samples obtained from the TCGA and tissue microarrays with clinic-pathological information. Taken together, as an essential gene for the survival of PTEN-inactive TNBC cells, WDHD1 could be a potential biomarker or a therapeutic target for TNBC.

Comparative effectiveness of first-line nab-paclitaxel versus paclitaxel monotherapy in triple-negative breast cancer

2019 ◽  
Vol 8 (14) ◽  
pp. 1173-1185 ◽  
Author(s):  
Patricia Luhn ◽  
Stephen Y Chui ◽  
“Angela” Fu-Chi Hsieh ◽  
Jingbo Yi ◽  
Almut Mecke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Similar Efficacy ◽  
Hazard Ratio ◽  
First Line ◽  
Risk Of Death ◽  
The Us ◽  
Similar Risk

Aim: This observational study evaluated the effectiveness of nab-paclitaxel versus paclitaxel monotherapy as first-line (1L) treatment for metastatic triple-negative breast cancer (mTNBC). Materials & methods: 200 patients from the US Flatiron Health electronic health record-derived database (mTNBC diagnosis, January 2011–October 2016) who received 1L nab-paclitaxel (n = 105) or paclitaxel (n = 95) monotherapy were included. Overall survival and time to next treatment were evaluated. Results: The adjusted overall survival hazard ratio was 0.98 (95% CI: 0.67–1.44), indicating a similar risk of death between groups. Adjusted time to next treatment hazard ratio was 0.89 (95% confidence interval: 0.62–1.29). Conclusion: Nab-paclitaxel and paclitaxel monotherapy showed similar efficacy, suggesting their interchangeability as 1L treatments for mTNBC.

Triple negative breast cancer: An institutional review

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22214-e22214
Author(s):  
M. Dioca ◽  
M. Savignano ◽  
L. Gimenez ◽  
L. Marino ◽  
C. Delfino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Menopausal Status ◽  
Stage I ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk

e22214 Background: Triple negative breast cancer (BC) is a distinct group of tumors that show common but heterogeneous morphologic, genetic, and immunophenotypic features. Despite differences in the definition and prevalence, it comprises 8% to 20% of all breast cancers and is associated with an aggressive clinical course with significant risk of either local or systemic relapse and subsequent increased risk of death on short term follow up (particularly in the first 5 years).We study the pathological characteristics and the clinical outcome of a cohort of 77 triple negative BC patients (pts) diagnosed at our Institution. Methods: Between January 1999 and September 2008, 77 (stage I to III) triple negative BC pts. were retrospectively analyzed. All pts had their receptor status, Her neu, ck-5, ck-6 and staining for EGFR by the same pathologist. Pathological parameters (Pp) analyzed were: status of axilary lymph nodes (LN), nuclear grade, histologic grade, mitotic index and vascular invasion and the use of antraciclins in the adjuvant setting. Univariate and multivariate analysis (proporcional hazard regression Cox model) for the Pp associated with relapse, and the log rank test to compare two curves of each Pp for disease free survival (DFS), and overall survival (OS) were performed. Results: The median age was 57.8 years (range 30–86 years).The median follow up time was 57.7 months (range, 4- 241). From 77 Pts. analized, 65 (84.4%) were basal-like and 43 (64.6%) of those were GH3. Stage at the time of presentation was: 16 (20,7%) stage I; 40 (51,9%) stage II; 21 (27,7%) stage III. Pre-menopausal status was 29,48% (23 pts.), and 61% (47 pts) were LN negative. Overall, relapse rate was 38.5 % (n= 30), 63 Pts (81.8%) are still alive. Median DFS was not reached. Global DFS and OS were 59% and 79% respectively, and status of LN was the only prognostic factor. LN- vs LN+ DFS (p< 00.02) and OS p (< 0.02).All others Pp analyzed were not statistically significative. Conclusions: Despite previous studies have demonstrated that triple negative is an independent marker of poor prognosis in BC as a whole, in the LN-negative, and LN-positive groups, in this basal like population only positive LN was an independent poor prognostic factor for DFS and OS. No significant financial relationships to disclose.

scholarly journals Mixed Effects and Mechanisms of Cannabinoids for Triple-Negative Breast Cancer Treatment

2021 ◽  
Author(s):  
Khanh Tran
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Progesterone Receptors ◽  
Antitumor Effects ◽  
Current Therapies ◽  
Cancer Types ◽  
Her 2 ◽  
Tumour Activity

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors (ER), progesterone receptors, and HER-2 receptors. Thus, TNBC tumours do not benefit from the current therapies targeting ER or HER-2. Therefore, there is an urgent need to develop novel treatment for this subtype of breast cancer. Marijuana is a common name given to Cannabis plants, a group of plants in the Cannabis genus of the Cannabaceae family. Cannabis plants are among the oldest cultivated crops, traced back at least 12,000 years and are well known for their multi-purpose usage, including medicinal purposes. The main active compounds extracted from Cannabis plants are 21-carbon-containing terpenophenolics, which are referred to as phytocannabinoids. Of these, the tetrahydrocannabinol (THC) group contains highly potent cannabinoids, including delta-9-tetrahydrocannabinol (∆9-THC) and delta-8-tetrahydrocannabinol (∆8-THC), which are the most abundant THCs and are largely responsible for psychological and physiological effects of marijuana. The use of Cannabis plants for medicinal purposes was first recorded in 2337 BC in China, where Cannabis plants were used to treat pains, rheumatism, and gout. Recently, several cannabinoids have been approved for a number of treatments, one of which is the treatment of nausea and vomiting caused by chemotherapy in cancer patients. Furthermore, increasing evidence shows that cannabinoids not only attenuate side effects due to cancer treatment, but might also potentially possess direct antitumor effects in several cancer types, including breast cancer. However, anti-tumour activity of marijuana has been variable in different studies and even promoted tumour growth in some cases. In addition, the mechanisms of cannabinoid action in cancer remain unclear. This review summarizes evidence about the mixed actions of cannabinoids in cancer in general and triple-negative breast cancer in particular.

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