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 Drug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5009
Author(s):  
Swetha Vasudevan ◽  
Ibukun A. Adejumobi ◽  
Heba Alkhatib ◽  
Sangita Roy Chowdhury ◽  
Shira Stefansky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Patient Specific ◽  
Network Structures ◽  
Breast Cancers ◽  
Drug Induced ◽  
Tcga Dataset

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancers which is treated mainly with chemotherapy and radiotherapy. Epidermal growth factor receptor (EGFR) was considered to be frequently expressed in TNBC, and therefore was suggested as a therapeutic target. However, clinical trials of EGFR inhibitors have failed. In this study, we examine the relationship between the patient-specific TNBC network structures and possible mechanisms of resistance to anti-EGFR therapy. Using an information-theoretical analysis of 747 breast tumors from the TCGA dataset, we resolved individualized protein network structures, namely patient-specific signaling signatures (PaSSS) for each tumor. Each PaSSS was characterized by a set of 1–4 altered protein–protein subnetworks. Thirty-one percent of TNBC PaSSSs were found to harbor EGFR as a part of the network and were predicted to benefit from anti-EGFR therapy as long as it is combined with anti-estrogen receptor (ER) therapy. Using a series of single-cell experiments, followed by in vivo support, we show that drug combinations which are not tailored accurately to each PaSSS may generate evolutionary pressure in malignancies leading to an expansion of the previously undetected or untargeted subpopulations, such as ER+ populations. This corresponds to the PaSSS-based predictions suggesting to incorporate anti-ER drugs in certain anti-TNBC treatments. These findings highlight the need to tailor anti-TNBC targeted therapy to each PaSSS to prevent diverse evolutions of TNBC tumors and drug resistance development.

scholarly journals Practical Approach to Triple-Negative Breast Cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 293-300 ◽  
Author(s):  
Vijayakrishna K. Gadi ◽  
Nancy E. Davidson
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Early Stage ◽  
Management Strategies ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Epidermal Growth ◽  
Proven Method

Triple negative is a term applied to breast cancers that do not meaningfully express the estrogen or progesterone hormone receptors or overexpress the human epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven method for systemic management of triple-negative breast cancer for both early-stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a comprehensive review of management strategies that are best supported by available data. We also review recent advances most likely to affect treatment of triple-negative breast cancer in the coming years with particular emphasis on targeted agents, biologics, and immunotherapy.

scholarly journals Immunotherapeutic Approaches in Triple-Negative Breast Cancer: State of the Art and Future Perspectives

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Karima Oualla ◽  
Loay Kassem ◽  
Lamiae Nouiakh ◽  
Lamiae Amaadour ◽  
Zineb Benbrahim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Poor Outcomes ◽  
Infiltrating Lymphocytes

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It accounts for 15%–20% of all breast cancers and is associated with an aggressive evolution and poor outcomes with the majority of recurrences and deaths occurring in the first 5 years. Chemotherapy remains the mainstay of treatment in the absence of effective targets, but the good understanding of immune tumor microenvironment, the identification of immune-related targets, and the role of tumor-infiltrating lymphocytes (TILs) in TNBC has allowed to develop promising immunotherapeutic strategies for this unique subset of breast cancer. Recently, immunotherapy is being extensively explored in TNBC and clinical trials have shown promising results. In this article, we tried to explain the rationale and mechanisms of targeting the immune system in TNBC, to report the results from recent clinical trials that put immunotherapy as a new standard of care in TNBC in addition to ongoing trials and future directions in the next decade.

Beyond triple-negative breast cancer and African ancestry: Tumor phenotypes among internationally diverse patient populations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1101-1101
Author(s):  
Evelyn Mawunyo Jiagge ◽  
Aisha Jibril ◽  
George Divine ◽  
Kofi K. Gyan ◽  
Jessica Miley Bensenhaver ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
African Ancestry ◽  
West African ◽  
Stem Cell Marker ◽  
Breast Cancers ◽  
East African ◽  
Increased Risk ◽  
West African Ancestry

1101 Background: Population-based incidence rates of breast cancers that are negative for estrogen receptor (ER), progesterone receptor (PR), and HER2/ neu(triple negative breast cancer {TNBC}) are higher among African American (AA) compared to White American (WA) women. Several studies show higher TNBC frequency among selected populations of African patients. The colonial-era trans-Atlantic slave trade resulted in shared West African ancestry between contemporary AA and Ghanaian (Gh) populations. The extent to which TNBC susceptibility is related to East African versus West African ancestry, and whether these associations extend to expression of other biomarkers such as Androgen Receptor (AR) and mammary stem cell marker ALDH1 is unknown. Methods: We used immunohistochemistry to assess ER, PR, HER2/ neu, AR and ALDH1 among WA (n = 153); AA (n = 76); Ethiopian (Eth)/East African (n = 90) and (Gh)/West African (n = 286) breast cancers through an IRB-approved international research program. Results: Mean age at breast cancer diagnosis was 43; 49; 60; and 57 years for the Eth; Gh; AA; and WA patients, respectively. Frequency of TNBC was significantly higher for AA and Gh patients (54% and 41%, respectively) compared to WA and Eth patients (23% and 15%, respectively); p < 0.001. These associations were unchanged when limited to patients age 50 and younger (47% and 49% for AA and Gh, respectively; versus 18% and 16% for WA and Eth, respectively); p < 0.001. Frequency of ALDH1 positivity was also higher for tumors from AA and Gh patients (32% and 36%, respectively) compared to those from WA and Eth patients (23% and 17%, respectively); p = 0.007. Significant differences were observed for distribution of AR positivity, which was 71%; 55%; 42% and 50% for the WA; AA; Gh; and Eth cases, respectively (p = 0.008). Conclusions: We found a correlation between extent of African ancestry and risk of particular BC phenotypes. West African ancestry was associated with increased risk of TNBC and breast cancers that are positive for ALDH1. Future studies of hereditary TNBC susceptibility among women with African ancestry are warranted.

Triple-Negative Breast Cancer

2019 ◽  
Author(s):  
Diane M. Radford ◽  
Jame Abraham ◽  
Stephen R. Grobmyer
Keyword(s):  
Breast Cancer ◽  
African American Women ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Cancer Breast ◽  
Gene Testing ◽  
Visceral Metastases ◽  
Epidermal Growth

Triple-negative breast cancers (TNBCs), negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, account for 15 to 20% of all female breast cancers. TNBC is heterogeneous based on gene expression microarray, and identification of TNBC subtypes and their behavior has the potential to enable more targeted, neoadjuvant, and adjuvant interventions. TNBCs usually are higher grade (Nottingham score 3) and are more common in younger, Hispanic, and African American women. They are more aggressive, have an increased likelihood of distant disease and mortality, are larger at presentation, and are more likely to be associated with lymph node metastases. Patients with TNBC are at a higher risk for visceral metastases early in the course of the disease. Genetic risk evaluation is recommended for patients with TNBC diagnosed at or before 60 years of age. Surgical management may be influenced by gene testing results. Standard adjuvant chemotherapy is anthracycline or taxane based. This review contains 5 figures, 8 tables, and 51 references. Key Words: adjuvant, BRCA, chemotherapy, hormone receptor negative, neoadjuvant, genetics, triple-negative breast cancer, breast neoplasm.

scholarly journals Disease-free Probability and Triple-Negative Breast Cancer

2012 ◽  
Vol 35 (1) ◽  
pp. 5-13
Author(s):  
Prakasit Chirappapha ◽  
Thongchai Sukarayothin ◽  
Yodying Wasuthit ◽  
Ronnarat Suvikapalornkul ◽  
Panuwat Lertsithichai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Local Recurrence ◽  
Triple Negative Breast Cancer ◽  
Distant Metastasis ◽  
Triple Negative ◽  
Free Probability ◽  
Growth Factor Receptor ◽  
Tumor Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients

Objective: To compare the probabilities of local recurrence and distant metastasis between women with triple-negative and non- triple negative breast cancers. Methods: Medical and pathological records of breast cancer patients treated between the years 2002 and 2006 were reviewed. Results: There were 256 patients with complete data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) expression determinations. There were 54 patients (21%) with triple-negative (ER-, PR-, HER2 -) cancers. Triple-negative patients were more likely to have larger tumors with higher histologic grade. The median fallow-up time was 4 years. The probabilities of local and distant recurrence were similar between the two groups of patients. Only two factors were independently and significantly associated with overall recurrence: tumor stage and tumor size. Conclusion: Triple-negative breast cancer did not have a higher risk for both local recurrence and distant metastasis when compared with non-triple negative cancer.

scholarly journals Current and emerging treatment options in triple-negative breast cancer

2011 ◽  
Vol 4 (1) ◽  
pp. 5
Author(s):  
Omer Dizdar ◽  
Kadri Altundag
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Histological Grade ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Immunohistochemical Analysis ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Chemotherapy Drugs

Triple-negative breast cancer is defined by the lack of estrogen receptor, progesterone receptor and HER2 expression with immunohistochemical analysis. Triplenegative breast cancers are poorly differentiated, characterized by high histological grade and occur at a younger age. Treatment options are limited as these tumors are naturally resistant to existing targeted therapies, i.e., endocrine treatment and trastuzumab. An improved understanding of the biology of TNBC has led to evaluation of DNA-damaging chemotherapy drugs and targeted agents, including poly (ADP-ribose) polymerase inhibitors, epidermal growth factor receptor inhibitors, angiogenesis inhibitors, etc., in the treatment of TNBC. This review focuses on outlining the current and emerging treatment options in patients with triple-negative breast cancer.

The Use of Atezolizumab + Nab-Paclitaxel for Women with PD- L1 Positive Advanced Triple-Negative Breast Cancer

2021 ◽  
Vol 8 (7) ◽  
pp. 36-43
Author(s):  
Vahideh Beygi Rezagholi ◽  
Sheby Elsa George ◽  
Gouthami. U
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Tumor Infiltrating Lymphocytes

Triple-negative breast cancer (TNBC) is an uncommon subtype of breast cancer that constitutes 15-20% of cases which has a poorer prognosis and lower survival rates (approximately 18 months or less with available treatments) compared to other types of breast cancer. As the name suggests, TNBC is immunohistologically marked by the lack of expression of factors namely estrogen receptors (ER), progesterone receptors (PR), and lack of overexpression and/or amplification of the human epidermal growth factor receptor 2 (HER2)/NEU gene. TNBC is characterized by high grades of Tumor-Infiltrating lymphocytes (TILs), programmed-death ligand 1 (PD-L1) expression, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) as observed in other cancers too. Hence, metastatic TNBC (mTNBC) therapy focuses on the advancement of immune checkpoint inhibitors which block the above immune checkpoint proteins. The use of Atezolizumab (anti-PD-L1) in combination with nab-paclitaxel (chemotherapy agent) has been marked as a relevant advance in the treatment of metastatic, PD-L1-positive TNBC. It is better to consider advanced and approved diagnostic (VENTANA PD-L1 SP142 assay) in patients who get benefit from treatment with Atezolizumab plus nab-paclitaxel. Keywords: Triple Negative Breast Cancer (TNBC), Atezolizumab, Nab-paclitaxel, Chemotherapy.

scholarly journals Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

2010 ◽  
Vol 28 (7) ◽  
pp. 1145-1153 ◽  
Author(s):  
Daniel P. Silver ◽  
Andrea L. Richardson ◽  
Aron C. Eklund ◽  
Zhigang C. Wang ◽  
Zoltan Szallasi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Single Agent ◽  
Progesterone Receptors ◽  
Gene Expression Signature ◽  
Induced Response ◽  
Breast Cancers ◽  
Brca1 Promoter Methylation ◽  
Common Pathogenesis

Purpose Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer share features suggesting common pathogenesis, we conducted a neoadjuvant trial of cisplatin in TNBC and explored specific biomarkers to identify predictors of response. Patients and Methods Twenty-eight women with stage II or III breast cancers lacking estrogen and progesterone receptors and HER2/Neu (TNBC) were enrolled and treated with four cycles of cisplatin at 75 mg/m2 every 21 days. After definitive surgery, patients received standard adjuvant chemotherapy and radiation therapy per their treating physicians. Clinical and pathologic treatment response were assessed, and pretreatment tumor samples were evaluated for selected biomarkers. Results Six (22%) of 28 patients achieved pathologic complete responses, including both patients with BRCA1 germline mutations;18 (64%) patients had a clinical complete or partial response. Fourteen (50%) patients showed good pathologic responses (Miller-Payne score of 3, 4, or 5), 10 had minor responses (Miller-Payne score of 1 or 2), and four (14%) progressed. All TNBCs clustered with reference basal-like tumors by hierarchical clustering. Factors associated with good cisplatin response include young age (P = .001), low BRCA1 mRNA expression (P = .03), BRCA1 promoter methylation (P = .04), p53 nonsense or frameshift mutations (P = .01), and a gene expression signature of E2F3 activation (P = .03). Conclusion Single-agent cisplatin induced response in a subset of patients with TNBC. Decreased BRCA1 expression may identify subsets of TNBCs that are cisplatin sensitive. Other biomarkers show promise in predicting cisplatin response.

scholarly journals Immunotherapy for Triple-Negative Breast Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2003
Author(s):  
Yifeng Cao ◽  
Chuyang Chen ◽  
Yi Tao ◽  
Weifeng Lin ◽  
Ping Wang
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Vaccine ◽  
Synergistic Effects ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Immune Checkpoints ◽  
Breast Cancer Patients

Triple-negative breast cancer (TNBC) is characterized by extensive tumor heterogeneity at both the pathologic and molecular levels, particularly accelerated aggressiveness, and terrible metastasis. It is responsible for the increased mortality of breast cancer patients. Due to the negative expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2, the progress of targeted therapy has been hindered. Higher immune response in TNBCs than for other breast cancer types makes immunotherapy suitable for TNBC therapy. At present, promising treatments in immunotherapy of TNBC include immune checkpoints (ICs) blockade therapy, adoptive T-cell immunotherapy, and tumor vaccine immunotherapy. In addition, nanomedicines exhibit great potential in cancer therapy through the enhanced permeability and retention (EPR) effect. Immunotherapy-involved combination therapy may exert synergistic effects by combining with other treatments, such as traditional chemotherapy and new treatments, including photodynamic therapy (PTT), photodynamic therapy (PDT), and sonodynamic therapy (SDT). This review focuses on introducing the principles and latest development as well as progress in using nanocarriers as drug-delivery systems for the immunotherapy of TNBC.

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