scholarly journals Breast Cancer: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Sheeba Cantanelli, MPAS, PA-C
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Parp Inhibitor ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Vitamin D Levels ◽  
The Impact

Sheeba Cantanelli, MPAS, PA-C, of UT Southwestern Medical Center, Simmons Comprehensive Cancer Center, discusses results from studies evaluating adjuvant therapy with a PARP inhibitor in BRCA-mutated HER2-negative metastatic breast cancer; immunotherapy in the treatment of early-stage triple-negative breast cancer; adjuvant capecitabine after neoadjuvant chemotherapy in triple-negative breast cancer; the addition of palbociclib to fulvestrant in HR-positive, HER2-negative advanced breast cancer; and the impact of vitamin D levels on outcomes. Reporting is provided by The ASCO Post.

321 Phase I clinical trial assessing the combination of systemic chemokine modulatory regimen targeting TLR3 with neoadjuvant chemotherapy in triple negative breast cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A347-A347
Author(s):  
Shipra Gandhi ◽  
Mateusz Opyrchal ◽  
Cayla Ford ◽  
Victoria Fitzpatrick ◽  
Melissa Grimm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase I ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Standard Dose ◽  
Surrogate Marker ◽  
Comprehensive Cancer Center ◽  
Cancer Center

BackgroundNeoadjuvant chemotherapy (NAC) with taxanes is the standard of care in triple negative breast cancer (TNBC). Intratumoral prevalence of CD8+ cytotoxic T-lymphocytes (CTLs) is associated with an improvement in relapse-free survival (RFS) and overall survival (OS), while regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) are associated with poor survival. Higher ratio of CTL/Treg is associated with higher probability of obtaining pathological complete response (pCR), a surrogate marker for RFS. Intratumoral production of CCL5, CXCL9, CXCL10 and CXCL11 is critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction. Previous studies have shown that CXCL9 expression in the pre-treatment breast tissue is associated with a three-fold higher rate of achieving pCR. Our preclinical data show that Chemokine modulating (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b, and celecoxib (COX-2 inhibitor) increases CTL-attracting, and decreases MDSC-, Treg-favoring chemokines, increasing CTL/Treg ratio in tumor microenvironment, with preferential tumor tissue activation than adjacent healthy tissues. We hypothesize that the combination of CKM with paclitaxel will result in infiltration of TNBC with CTLs, and along with doxorubicin/cyclophosphamide (AC), result in higher pCR, translating into improved RFS and OS.MethodsIn this phase I study NCT04081389, eligibility includes age ≥18 years, confirmed resectable TNBC, radiographically measurable disease ≥1 cm, ECOG PS ≤ 2, adequate organ and marrow function. Patients with autoimmune disease, serious mood disorders, invasive carcinoma within 3 years, history of peptic ulcers or hypersensitivity to NSAIDs will be excluded. We plan to treat three patients with early stage TNBC with paclitaxel 80 mg/m2 IV weekly for 12 weeks, rintatolimod 200 mg IV, celecoxib 200 mg oral twice daily, and accelerated titration of IFN-α2b at doses 0, 5, or 10 million units (MU)/m2 [Dose Levels (DL) 1, 2 and 3 respectively] on days 1–3 (no intra-patient dose escalation) in weeks 1–3. Dose-limiting toxicity (DLT) is defined as grade 3 or higher toxicities within the first 3 weeks. Any DLT will mandate recruitment per the 3+3 model. If no DLT, three patients will be enrolled at DL 4 at 20 MU/m2 IFN- α2b. This will be followed by standard dose-dense AC, and then surgery. The primary endpoint is safety and tolerability of combination and to identify the appropriate DL of CKM and paclitaxel for extended efficacy study. The secondary endpoints include investigation of efficacy (pCR and breast MRI response), along with RFS and OS. Intratumoral biomarkers will be analyzed in an exploratory manner.ResultsN/AConclusionsN/ATrial RegistrationNCT04081389Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-73718.

scholarly journals Transcriptome Analysis Derives a Novel Prognostic 7-mRNA Signature in Early-Stage Triple-Negative Breast Cancer

2021 ◽  
Author(s):  
Yun-Song Yang ◽  
Yi-Xing Ren ◽  
Shuang Hao ◽  
Xiao-En Xu ◽  
Xi Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Cox Regression ◽  
Early Stage ◽  
Distant Recurrence ◽  
Cancer Center ◽  
Transcriptome Data ◽  
Normal Tissues

Abstract Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease and patients with early-stage TNBCs have distinct likelihood of distant recurrence. Methods: In this study, We extracted transcriptome data for 189 pathologically confirmed pT1-2 node-negative TNBC patients at Fudan University Shanghai Cancer Center. Candidate mRNAs were filtered, which was followed by differential expressed mRNAs analysis, survival analysis, and LASSO Cox regression model. All-subsets regression program was used for constructing a multi-mRNA signature in the training set (n=159); the accuracy and prognostic value were then validated using an independent validation set (n=158). Results: Here, we profiled the transcriptome data from 189 early-stage TNBC patients along with 50 paired normal tissues, and developed a prognostic signature based on seven mRNAs (ACAN, KRT5, TMEM101, LCA5, RPP40, LAGE3, CDKL2).In both the training (n=159) and validation cohorts (n=158), the signature could identify patients with relatively high recurrence risks and serve as an independent prognostic factor. Furthermore, the signature had better prognostic value than traditional clinicopathological features in both sets. Among the seven mRNAs, TMEM101 was identified as a prognostic biomarker of early-stage TNBC. Additional cell experiments suggested that TMEM101 could facilitate migration and proliferation of TNBC cells. Conclusions: Our 7-mRNA signature could accurately predict recurrence risks of early-stage TNBCs. Clinical and genomic low risk TNBC patients may safely avoid adjuvant chemotherapy.

The Impact of Platinum-Containing Chemotherapies in Advanced Triple-Negative Breast Cancer: Meta-Analytical Approach to Evaluating Its Efficacy and Safety

2021 ◽  
pp. 1-10
Author(s):  
Rui Yang ◽  
You-Yang Shi ◽  
Xiang-Hui Han ◽  
Sheng Liu
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Cochrane Library ◽  
Control Group ◽  
Chemotherapy Group ◽  
Significant Difference ◽  
The Impact

<b><i>Background:</i></b> Triple-negative breast cancer (TNBC), the most common type of breast cancer, is associated with poor patient prognosis. Platinum-containing chemotherapies are commonly used in the treatment and prevention of advanced TNBC. <b><i>Objectives and Methods:</i></b> To systematically evaluate the effectiveness and safety of platinum-containing chemotherapies in patients with advanced TNBC, we searched several databases, including PubMed, Medline, Embase, ClinicalTrials.gov, Cochrane Library, CNKI, CBM, and the Chinese Cochrane Center, to collect published randomized controlled clinical studies of platinum-containing chemotherapies for advanced TNBC before November 2020. The meta-analysis was performed using Review Manager version 5.3. To assess effectiveness and safety, dichotomous and continuous variables were assessed using odds ratio (OR) and mean difference (MD), respectively, with 95% CI. <b><i>Results:</i></b> A total of 1,222 patients with advanced TNBC were enrolled in 11 eligible trials, including 489 patients in the treatment group (platinum-containing) and 447 patients in the control group (non-platinum-containing). We also retrieved information whether a PARP inhibitor was combined with platinum-containing chemotherapy for patients with metastatic TNBC and identified 224 patients who received a PARP inhibitor combined with platinum-containing chemotherapy and 62 patients in the platinum-containing group who did not. The platinum-containing chemotherapy group had a significantly better objective response rate (OR 1.43, 95% CI 1.20–1.71, <i>p</i> &#x3c; 0.001) and longer progression-free survival (PFS; MD 1.15, 95% CI 0.03–2.28, <i>p</i> &#x3c; 0.05) than the non-platinum-containing chemotherapy group. However, there was no significant difference in overall survival (OS) of patients with advanced TNBC between the two groups (MD 2.04, 95% CI –0.83 to 4.91, <i>p</i> &#x3e; 0.05). Related adverse effects of platinum-containing chemotherapies involved gastrointestinal reaction, myelosuppression and liver function damage. Platinum-containing chemotherapies were not associated with an increased incidence of adverse side effects compared with non-platinum-containing chemotherapies, with the exception of nausea and vomiting (OR 2.22, 95% CI 1.10–4.46, <i>p</i> &#x3c; 0.05). Furthermore, the addition of the PARP inhibitor iniparib to gemcitabine and carboplatin treatment improved the rate of clinical benefit, OS and PFS. <b><i>Conclusions:</i></b> Platinum-containing chemotherapy remains a highly recommended therapeutic regimen due to greater effectiveness and tolerance for patients with advanced TNBC.

scholarly journals Mapping Intellectual Structures and Research Hotspots of Triple Negative Breast Cancer: A Bibliometric Analysis

2022 ◽  
Vol 11 ◽  
Author(s):  
Kai-jun Hao ◽  
Xiao Jia ◽  
Wen-ting Dai ◽  
Ze-min Huo ◽  
Hua-qiang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Parp Inhibitor ◽  
Cancer Center ◽  
Burst Detection ◽  
Scientific Publications ◽  
Tumor Cell Migration ◽  
Research Hotspots

BackgroundTriple negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype with a poor prognosis due to its extremely aggressive nature and lack of effective treatment options. This study aims to summarize the current hotspots of TNBC research and evaluate the TNBC research trends, both qualitatively and quantitatively.MethodsScientific publications of TNBC-related studies from January 1, 2010 to October 17, 2020 were obtained from the Web of Science database. The BICOMB software was used to obtain the high-frequency keywords layout. The gCLUTO was used to produce a biclustering analysis on the binary matrix of word-paper. The co-occurrence and collaboration analysis between authors, countries, institutions, and keywords were performed by VOSviewer software. Keyword burst detection was performed by CiteSpace.ResultsA total of 12,429 articles related to TNBC were identified. During 2010-2020, the most productive country/region and institution in TNBC field was the USA and The University of Texas MD Anderson Cancer Center, respectively. Cancer Research, Journal of Clinical Oncology, and Annals of Oncology were the first three periodicals with maximum publications in TNBC research. Eight research hotspots of TNBC were identified by co-word analysis. In the core hotspots, research on neoadjuvant chemotherapy, paclitaxel therapy, and molecular typing of TNBC is relatively mature. Research on immunotherapy and PARP inhibitor for TNBC is not yet mature but is the current focus of this field. Burst detection of keywords showed that studies on TNBC proteins and receptors, immunotherapy, target, and tumor cell migration showed bursts in recent three years.ConclusionThe current study revealed that TNBC studies are growing. Attention should be paid to the latest hotspots, such as immunotherapy, PARP inhibitors, target, and TNBC proteins and receptors.

scholarly journals Does Race Affect Outcomes in Triple Negative Breast Cancer?

2010 ◽  
Vol 4 ◽  
pp. 117822341000400 ◽  
Author(s):  
Jasgit C. Sachdev ◽  
Saira Ahmed ◽  
Muhammad M. Mirza ◽  
Aamer Farooq ◽  
Lori Kronish ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Menopausal Status ◽  
Cancer Center ◽  
Early Event ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Significant Difference ◽  
The Impact

Background There is discordance among studies assessing the impact of race on outcome of patients with Triple Negative Breast Cancer (TNBC). We assessed survival outcomes for African American (AA) versus Caucasian (CA) women with TNBC treated at an urban cancer center in Memphis, TN with a predominant AA patient population. Methods Patients with Stage I-III TNBC were identified from our breast database. Event free survival (EFS) and Breast cancer specific survival (BCSS) were the primary outcome measures. Cox proportional hazards models were fitted for EFS and BCSS. Results Of the 124 patients, 71% were AA. No significant association between race and stage ( P = 0.21) or menopausal status ( P = 0.15) was observed. Median age at diagnosis was significantly lower for AA versus CA women (49.5 vs. 55 years, P = 0.024). 92% of the patients received standard neo/adjuvant chemotherapy, with no significant difference in duration and type of chemotherapy between the races. With a median follow up of 23 months, 28% of AA vs. 19% of CA women had an event ( P = 0.37). 3 year EFS and BCSS trended favorably towards CA race (77% vs. 64%, log rank P = 0.20 and 92% vs. 76%, P = 0.13 respectively) with a similar trend noted on multiple variable modeling (EFS: HR 0.62, P = 0.29; BCSS: HR 0.36, P = 0.18). AA women ≥50 years at diagnosis had a significantly worse BCSS than the CA women in that age group ( P = 0.012). Conclusion Older AA women with TNBC have a significantly worse breast cancer specific survival than their CA counterparts. Overall, there is a trend towards lower survival for AA women compared to Caucasians despite uniformity of tumor phenotype and treatment. The high early event rate, irrespective of race, underscores the need for effective therapies for women with TNBC.

scholarly journals Breast – conserving Surgery in Early – Stage Triple – Negative Breast Cancer: Is There a Higher Risk of Locoregional Recurrence?

2012 ◽  
Vol 12 (1) ◽  
pp. 11-14
Author(s):  
Jelena Maksimenko ◽  
Arvids Irmejs ◽  
Genadijs Trofimovics ◽  
Edvins Miklasevics
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Locoregional Recurrence ◽  
Triple Negative ◽  
Early Stage ◽  
Statistical Significance ◽  
Group Versus ◽  
Significant Difference ◽  
The Impact ◽  
Mastectomy Group

SummaryIntroduction.Triple- negative breast cancer (TNBC) is an aggressive disease with poor prognosis and high risk of locoregional recurrence (LRR).Aim of the Study.Is to examine the impact of type of surgery on locoregional recurrence in women with early- stage invasive triplenegative breast cancer (TNBC).Materials and Methods.A total of 68 women with stage I- II (T1N0M0, T2N0M0, T1N1M0, or T2N1M0) invasive, unifocal TNBC with hitologically tumor- free surgical margins were included. Patients were stratified into two groups according to surgical treatment, breast- conserving therapy (BCT) in 36 of 68 patients versus mastectomy in 32 of 68 patients. The two common founder mutations in BRCA1 (4153delA and 5382insC) in Latvia were tested using a multiplex- specific polymerase chain reaction(PCR) assay. Clinicopathological data and survival outcomes were analyzed.Results.There were no statistically significant differences in relation to age, stage, tumor size, histological type, tumor grade and nodal status between two groups. 24 patients (77.4%) in the mastectomy group and 27(75%) patients in the BCT group received chemotherapy, these difference was not statistically significant. 10(32.2%) of 32 patients in the mastectomy group and 34(94%) of 36 patients in the BCT group received postoperative radiation (P< 0.0001). There was no statistically significant difference noted in rates of distant metastases (5 cases (16.1%) in the mastectomy group versus 4 cases (11.1%) in the BCT group; P < 0.725)). A higher proportion of patients in the BCT group experienced locoregional recurrence compared with patients in the mastectomy group (3 cases (8.3%) versus 0 case (0%), respectively), but this did not reach statistical significance (P< 0.241). It was found that the tumor histology, grade, age at presentation and BRCA1 mutation status were not significant predictors of local recurrence. There was no significant difference in 5- year breast cancer- related survival between two groups (P>0.05).Conclusions.Patients after BCT have a higher locoregional recurrence rates compared to mastectomy, but this did not reach statistical significance. According to our study data BCT is not a contraindication in the TNBC.

Dissecting the Heterogeneity of Triple-Negative Breast Cancer

2012 ◽  
Vol 30 (15) ◽  
pp. 1879-1887 ◽  
Author(s):  
Otto Metzger-Filho ◽  
Andrew Tutt ◽  
Evandro de Azambuja ◽  
Kamal S. Saini ◽  
Giuseppe Viale ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Parp Inhibitor ◽  
High Sensitivity ◽  
Phase Iii ◽  
Breast Cancers ◽  
Cancer Subtypes

Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers. It is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. TNBC is associated with a significantly higher probability of relapse and poorer overall survival in the first few years after diagnosis when compared with other breast cancer subtypes. This is observed despite its usual high sensitivity to chemotherapy. In the advanced setting, responses observed with chemotherapy lack durability. Early-stage clinical studies suggested impressive potential when a poly (ADP-ribose) polymerase (PARP) inhibitor is given for the treatment of advanced TNBC with BRCA gene dysfunction. The molecular complexity of TNBC has led to proposed subclassifications, which will be of great value for the development of targeted therapies. In this review, we discuss the biology of TNBC at the pathologic and the molecular levels. We also elaborate on the role of systemic therapies and the results of the first phase III clinical trial evaluating the addition of iniparib, a novel investigational anticancer agent that does not possess characteristics typical of the PARP inhibitor class, in combination with chemotherapy in advanced TNBC.

scholarly journals The Early-Stage Triple-Negative Breast Cancer Landscape Derives a Novel Prognostic Signature and Therapeutic Target

2021 ◽  
Author(s):  
Yun-Song Yang ◽  
Yi-Xing Ren ◽  
Cheng-Lin Liu ◽  
Shuang Hao ◽  
Xiao-En Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Target ◽  
Prognostic Value ◽  
Triple Negative ◽  
Cox Regression ◽  
Early Stage ◽  
Cancer Center ◽  
Transcriptome Data ◽  
Prognostic Signature

Abstract Purpose: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. Patients with early-stage TNBCs have distinct likelihood of distant recurrence. Current therapeutic guidance is still limited.Methods: We extracted transcriptome data for 189 pathologically confirmed pT1-2N0M0 TNBC patients at Fudan University Shanghai Cancer Center. Candidate mRNAs were filtered, which was followed by differential expressed mRNAs analysis, survival analysis, and LASSO Cox regression model. All-subsets regression program was used for constructing a multi-mRNA signature in the training set (n=159); the accuracy and prognostic value were then validated using an independent validation set (n=158). Results: Here, we profiled the transcriptome data from 189 early-stage TNBC patients along with 50 paired normal tissues. Early-stage TNBCs are featured of basal-like and immune-suppressed subtype and homologous recombination ability deficiency. We developed a prognostic signature contained seven mRNAs from transcriptome data (ACAN, KRT5, TMEM101, LCA5, RPP40, LAGE3, CDKL2). In both the training (n=159) and validation cohorts (n=158), the signature could identify patients with relatively high recurrence risks and serve as an independent prognostic factor. The signature had better prognostic value than traditional clinicopathological features in both sets. Among the seven mRNAs, TMEM101 is highly expressed in TNBC and represents a potential therapeutic target. Inhibition of TMEM101 impaired tumor progression.Conclusions: Our 7-mRNA signature could accurately predict recurrence risks of early-stage TNBCs. Clinical and genomic low risk TNBC patients may have the opportunity to avoid adjuvant chemotherapy

scholarly journals 320 Phase IIa study of alpha-DC1 vaccine against HER2/HER3, chemokine modulation regimen and pembrolizumab in patients with asymptomatic brain metastasis from triple negative or HER2+ breast cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A346-A346
Author(s):  
Shipra Gandhi ◽  
Peter Forsyth ◽  
Mateusz Opyrchal ◽  
Kamran Ahmed ◽  
Hung Khong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Disease Progression ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Th1 Cells ◽  
Her2 Breast Cancer

BackgroundBrain metastases develop in up to 50% patients with metastatic triple negative breast cancer (TNBC) and HER2+ BC and are an increasing source of morbidity and mortality. HER3, overexpressed in triple negative and HER2+ brain metastatic breast cancer (BMBC), is a resistance factor to HER2-targeted therapies and a driver of CNS metastasis. Disease progression is associated with loss of anti-HER2/3 immunity. We have demonstrated that alphaDC1 loaded with glioma-specific peptides induce intratumoral production of chemokines (CXCL9, CXCL10, CXCL11, CCL5) which attract CXCR3- and CCR5- expressing cytotoxic T-lymphocytes (CTLs) and T-helper 1 (Th1) cells to brain tumors, inducing clinical responses and long-term disease stabilization in patients with aggressive recurrent primary brain tumors. Our preclinical data show that Chemokine modulating (CKM) regimen [rintatolimod, interferon (IFN)-α2b and COX-2 inhibitor] also selectively attracts effector CTLs and Th1 cells (but not suppressive regulatory T-cells or myeloid-derived suppressor cells) into tumors. Importantly, CKM preferentially promotes CTL migration into tumor rather than healthy tissues, providing rationale for its systemic use. We hypothesize that anti-HER2/3 type 1 polarized DC1s in combination with CKM and anti-PD1 will result in improved Th1/CTL response against HER2/3 epitopes, reduce brain recurrence and systemic progression.MethodsThis is a phase II single-arm, non-randomized multicenter study (NCT04348747). Eligibility includes patients with triple negative and HER2+ BMBC ≥ 18 years, ECOG PS ≤ 1, normal marrow and organ function with asymptomatic untreated brain metastases who receive αDC1 q2 weeks x 3, with CKM [200 mg IV rintatolimod, IFN-α 20 million units/m2 IV, celecoxib 200 mg oral BID] on days 1-3 with second and third dose of αDC1, followed by pembrolizumab 200 mg IV. Thereafter, pembrolizumab is given every 3 weeks, along with αDC1 and CKM every 3 months as booster dose until disease progression, intolerable side effects or withdrawal from study, or up to 24 months. Baseline and 3-week post-CKM treatment peripheral (non-CNS) biopsies are required for six patients. Primary objective is CNS response rate (RR) using RANO-BM criteria. If no CNS response is observed after 12 patients, study will be terminated. If ≥ 1 response observed, then 9 more patients will be enrolled, for a total of 21 patients. If ≥ 3 CR observed, the proposed therapy will be considered promising for further study. Secondary objectives include non-CNS RR per RECIST v1.1, median CNS, non-CNS and overall progression-free survival, overall survival and safety. Analysis of change in intratumoral biomarkers is an exploratory objective.ResultsN/AConclusionsN/ATrial RegistrationNCT04348747Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-19-04120.

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