scholarly journals Spatial Profiling Identifies Prognostic Features of Response to Adjuvant Therapy in Triple Negative Breast Cancer (TNBC)

2022 ◽  
Vol 11 ◽  
Author(s):  
Arutha Kulasinghe ◽  
James Monkman ◽  
Esha T. Shah ◽  
Nicholas Matigian ◽  
Mark N. Adams ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Differential Expression Analysis ◽  
Tumour Microenvironment ◽  
Chemotherapy Response ◽  
Prognostic Features ◽  
Chemotherapeutic Response ◽  
Er Alpha

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has few effective treatment options due to its lack of targetable hormone receptors. Whilst the degree of tumour infiltrating lymphocytes (TILs) has been shown to associate with therapy response and prognosis, deeper characterization of the molecular diversity that may mediate chemotherapeutic response is lacking. Here we applied targeted proteomic analysis of both chemotherapy sensitive and resistant TNBC tissue samples by the Nanostring GeoMx Digital Spatial Platform (DSP). By quantifying 68 targets in the tumour and tumour microenvironment (TME) compartments and performing differential expression analysis between responsive and non-responsive tumours, we show that increased ER-alpha expression and decreased 4-1BB and MART1 within the stromal compartments is associated with adjuvant chemotherapy response. Similarly, higher expression of GZMA, STING and fibronectin and lower levels of CD80 were associated with response within tumour compartments. Univariate overall-survival (OS) analysis of stromal proteins supported these findings, with ER-alpha expression (HR=0.19, p=0.0012) associated with better OS while MART1 expression (HR=2.3, p=0.035) was indicative of poorer OS. Proteins within tumour compartments consistent with longer OS included PD-L1 (HR=0.53, p=0.023), FOXP3 (HR=0.5, p=0.026), GITR (HR=0.51, p=0.036), SMA (HR=0.59, p=0.043), while EPCAM (HR=1.7, p=0.045), and CD95 (HR=4.9, p=0.046) expression were associated with shorter OS. Our data provides early insights into the levels of these markers in the TNBC tumour microenvironment, and their association with chemotherapeutic response and patient survival.

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.

Triple Negative Breast Cancer Pathologic Diagnosis and Current Chemotherapy Treatment Options

2014 ◽  
Vol 10 (01) ◽  
pp. 25
Author(s):  
Bernardo L Rapoport ◽  
Simon Nayler ◽  
Georgia S Demetriou ◽  
Shun D Moodley ◽  
Carol A Benn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Treatment Options ◽  
Single Agent ◽  
Pathologic Complete Response ◽  
Metastatic Breast ◽  
Pathologic Diagnosis ◽  
Metastatic Setting

Triple negative breast cancer (TNBC) comprises 12–20 % of all breast cancers and are a heterogeneous group of tumors, both clinically and pathologically. These cancers are characterized by the lack of expression of the hormone receptors estrogen receptor (ER) and progesterone receptor (PR), combined with the lack of either overexpression or amplification of the human epidermal growth factor receptor-2(HER2)gene. Conventional cytotoxic chemotherapy and DNA damaging agents continue to be the mainstay of treatment of this disease in the neoadjuvant, adjuvant, and metastatic setting. The lack of predictive markers in identifying potential targets for the treatment of TNBC has left a gap in directed therapy in these patients. Platinum agents have seen renewed interest in TNBC based on an increasing body of preclinical and clinical data suggesting encouraging activity. However, comparisons between chemotherapy regimens are mostly retrospective in nature and the best agents or drug combinations for TNBC have not been established in prospective randomized trials. Numerous studies have now shown that TNBC has significantly higher pathologic complete response (pCR) rates compared with hormone receptor positive breast cancer when treated with neoadjuvant chemotherapy, and pCR correlates well with better outcomes for these patients. Patients with TNBC account for a larger number of deaths in the setting of metastatic breast cancer. There is no preferred treatment for the first-line metastatic setting. Although individual agents are recommended, given the often aggressive nature of TNBC and the presence of extensive visceral disease, the use of a combination of drugs, rather than a single agent, is often advocated. This review article will outline the pathologic diagnosis of TNBC and the treatment options available to these patients in the neoadjuvant, adjuvant, and metastatic setting, including an assessment of future directions of treatment.

Pathologic response to neoadjuvant therapy with nabpaclitaxel plus carboplatin followed by anthracycline regimen in triple-negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12117-e12117
Author(s):  
Juan David Cardenas ◽  
Carmen Esteban ◽  
Iciar Garcia Carbonero ◽  
Adriana Rosero ◽  
Katherin Martinez Barroso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Conservative Surgery ◽  
Stage Ii ◽  
Hematologic Toxicity

e12117 Background: Triple-negative breast cancer (TNBC) remains a poor prognosis subtype of breast cancer (BC). We are lacking of definitive effective combinations in this tumor. So, it is warranted to explore new combinations. Neo-adjuvant setting is one of the most effective scenarios to explore a treatment efficacy. We aimed to evaluate efficacy of Nab-paclitaxel plus Carboplatin followed byanthracycline regimen by pathologic complete response (pCR: no disease in breast and axilla) in women with TNBC. Secondary endpoints were toxicity profile and breast conserving surgery. Methods: Women with stage II or III disease were included. Hormone receptors and HER2 negativity was confirmed by immunohistochemistry and/or FISH. Patients received Nab-paclitaxel 125 mg/m2 plus Carboplatin AUC 2 intravenously on days 1, 8 every 21 for four cycles followed by Epirubicin 90 mg/m2 and Cyclophosphamide 600 mg/m2 intravenously every 2 weeks for 4 cycles and subsequent surgery. Breast Magnetic Resonance was done in all cases at diagnosis and before surgery. We obtained informed consent from all patients. Results: Thirty-two patients with confirmed clinical stage II (56.3%) or III (43.7%) TNBC were treatedbetween January 2015 and February 2019. The median age of the patients was 53.1 years (30.3-77.6 years). The average of received chemotherapy was 12 doses (7-14). The mean dose of nab-paclitaxel plus carboplatin was 8 doses. All patients received surgery with or without radiotherapy. There was only one case (3.1%) of progression during neoadjuvant treatment. The rate of pCR was 50% (16) in breast and axilla, partial response 43.8% (14) and stable disease 3.1% (1). Conservative surgery was performed in 50% of patients (16). The 3/4 grade toxicities were asthenia 3.1% (1), nausea/vomiting 6.3% (2), thrombocytopenia 6.3% (2), leukopenia 6.3% (2), neutropenia 40.6% (13), febrile neutropenia 6.3% (2), diarrhea 3.1% (1), allergy 3.1% (1), peripheral neurotoxicity 3.1% (1). After a median follow-up of 18.3 months (5.0–41.9) 93.8% (30) of patients are alive. Two patients (6.3%) had early local relapse and distant relapse, respectively, and are deceased due to progression disease. Conclusions: Nab-paclitaxel plus carboplatin followed by anthracycline regimencombination as neoadjuvant treatment in TNBC achieved an encouraging rate of pCR, allowing conservative surgery in half of our patients. Toxicities were not severe in most patients and hematologic toxicity was manageable with G-CSF.

scholarly journals Novel role of PELP1 in regulating chemotherapy response in mutant p53-expressing triple negative breast cancer cells

2015 ◽  
Vol 150 (3) ◽  
pp. 487-499 ◽  
Author(s):  
Samaya R. Krishnan ◽  
Binoj C. Nair ◽  
Gangadhara R. Sareddy ◽  
Sudipa Saha Roy ◽  
Mohan Natarajan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Chemotherapy Response ◽  
Mutant P53
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