49P The role of circulating cell-free DNA measured by a simple fluorescent assay to predict relapse in triple negative breast cancer receiving neoadjuvant chemotherapy

Background Triple-negative breast cancer (TNBC) is associated with higher aggressiveness and mortality than hormone-positive breast cancer because of the lack of approved therapeutic targets. Patients with TNBC who attain a pathological complete response (pCR) after neoadjuvant chemotherapy have improved survival. Platinum-based agents show promising activity in TNBC; however, their use remains controversial. We conducted a meta-analysis to assess the role of platinum-based agents in neoadjuvant chemotherapy in patients with TNBC. Methods We performed an extensive literature search of the Pubmed, Embase, and Cochrane databases. We calculated pooled odds ratios (OR) with 95% confidence intervals (CI) for the identified studies. Results Eight randomized controlled trials with 1345 patients were included in the analysis. The addition of platinum-based agents improved pCR compared with neoadjuvant therapy based on anthracyclines, cyclophosphamide, taxanes, and fluorouracil (49.1% vs. 35.9%; OR: 1.87, 95% CI: 1.23–2.86). Hematological adverse events were similar in both groups, except for more thrombocytopenia in the platinum-based group (OR: 7.96, 95% CI: 3.18–19.93). Conclusion The addition of platinum-based agents to neoadjuvant chemotherapy improved pCR rates in patients with TNBC, with a slight increase in hematological toxicities. Platinum-based agents might thus be an accessible and economically viable option in patients with TNBC.

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PROGNOSIS OF NEOADJUVANT CHEMOTHERAPY EFFICACY WITH IMMUNOBIOLOGIC TUMOR MARKERS IN PATIENTS WITH TRIPLE NEGATIVE BREAST CANCER

Likarska sprava ◽

10.31640/jvd.5-6.2019(5) ◽

2019 ◽

pp. 46-54

Author(s):

S. A. Lyalkin ◽

N. O. Verevkina ◽

L. A. Syvak

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Fold Increase ◽

Predictive Role ◽

High Level ◽

Chemotherapy Efficacy ◽

Cd4 Lymphocytes

Treatment of patients with triple negative breast cancer (TNBC) remains one of the most difficult problems in clinical oncology. Despite the negative prognosis for TNBC, there exists the group of patients with better response to the therapy and better prognosis, which proves the heterogenity of TNBC. The aim of the study was to evaluate the predictive role of tumor infiltrative lymphocytes (TIL) and their subpopulations (CD4+, CD8+ and FOXP3) in patients with TNBC. The predictive role of clinical, morphologic and immunohystochemical tumor features on neoadjuvant chemotherapy (NACT) efficacy was assessed in 52 TNBC patients. The risk of incomplete pathomorphologic response after NACT is related with 2 biomarkers: level of TIL and stromal CD4+ lymphocytes. The increase of TIL level decreases of the risk of incomplete pathomorphologic response (P = 0.01), ОR = 0.07 (95 % CІ 0.01–0.55) while standartization on CD4+ level. The high level of TIL at the time of diagnosis significantly decreases the risk of incomplete pathomorphologic response (OR = 0,2; P = 0,02). The group of patients with the ratio of stromal lymphocytes CD4low/CD8low had the eight-fold increase of the risk of incomplete pathomorphologic response comparing with the group with the ratio CD4high/CD8high (ОR = 8,0; Р = 0,03); the patient with the ratio stromal lymphocytes CD8low/ FOXP3low had the almost two-fold increase of the risk of incomplete pathomorphologic response comparing with the group with the ratio CD8high/FOXP3high (ОR = 2,1; Р = 0,03).

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The role of neoadjuvant chemotherapy of triple-negative breast cancer in St. Petersburg City Clinical Oncological Dispensary

Tumors of female reproductive system ◽

10.17650/1994-4098-2016-12-2-26-34 ◽

2016 ◽

Vol 12 (2) ◽

pp. 26-34 ◽

Cited By ~ 1

Author(s):

A. G. Manikhas ◽

R. N. Babeshkin ◽

R. M. Paltuev ◽

G. M. Manikhas

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative

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Prognostic Influence of Residual Tumor-Infiltrating Lymphocyte Subtype After Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.636716 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jesse Lopes da Silva ◽

Lucas Zanetti de Albuquerque ◽

Fabiana Resende Rodrigues ◽

Guilherme Gomes de Mesquita ◽

Priscila Valverde Fernandes ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Immune Cell ◽

Clinical Stage ◽

Residual Tumor ◽

Tissue Microarrays ◽

Curative Surgery

ObjectiveThis study aimed to examine the prevalence and prognostic role of tumor microenvironment (TME) in triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NACT) through immunohistochemical characterization.MethodsThe internal database of the Brazilian National Cancer Institute for women diagnosed with TNBC who underwent NACT and thereafter curative surgery between January 2010 and December 2014 was queried out. Core biopsy specimens and tissue microarrays containing surgical samples of TNBC from 171 and 134 women, respectively, were assessed by immunohistochemistry for CD3, CD4, CD8, CD14, CD56, CD68, CD117, FOXP3, PD-1, PD-L1, and PD-L2. Immune cell profiles were analyzed and correlated with response and survival.ResultsMean age was 50.5 years, and most cases were clinical stage III [143 cases (83.6%)]. According to the multivariate analysis, only Ki67 and clinical stage significantly influenced the pattern of response to systemic treatment (p = 0.019 and p = 0.033, respectively). None of the pre-NACT IHC markers showed a significant association with event-free survival (EFS) or overall survival (OS). As for post-NACT markers, patients with high CD14 had significantly shorter EFS (p = 0.015), while patients with high CD3 (p = 0.025), CD4 (p = 0.025), CD8 (p = 0.030), CD14 (p = 0.015), FOXP3 (p = 0.005), high CD4/FOXP3 (p = 0.034), and CD8/FOXP3 (p = 0.008) showed longer EFS. Only high post-NACT CD4 showed significantly influenced OS (p = 0.038).ConclusionThe present study demonstrated that the post-NACT TIL subtype can be a determining factor in the prognosis of patients with TNBC.

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Abstract GS3-07: Genome-wide copy number analysis of chemotherapy-resistant metastatic triple-negative breast cancer from cell-free DNA

10.1158/1538-7445.sabcs17-gs3-07 ◽

2018 ◽

Cited By ~ 1

Author(s):

DG Stover ◽

HA Parsons ◽

G Ha ◽

S Freeman ◽

B Barry ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Copy Number ◽

Triple Negative ◽

Copy Number Analysis ◽

Cell Free Dna ◽

Free Dna ◽

Genome Wide

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Association of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2017.76.0033 ◽

2018 ◽

Vol 36 (6) ◽

pp. 543-553 ◽

Cited By ~ 67

Author(s):

Daniel G. Stover ◽

Heather A. Parsons ◽

Gavin Ha ◽

Samuel S. Freeman ◽

William T. Barry ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Copy Number ◽

Triple Negative ◽

Copy Number Alterations ◽

Cell Free Dna ◽

Primary Tumors ◽

Free Dna ◽

Genome Wide ◽

Somatic Copy Number Alterations

Purpose Cell-free DNA (cfDNA) offers the potential for minimally invasive genome-wide profiling of tumor alterations without tumor biopsy and may be associated with patient prognosis. Triple-negative breast cancer (TNBC) is characterized by few mutations but extensive somatic copy number alterations (SCNAs), yet little is known regarding SCNAs in metastatic TNBC. We sought to evaluate SCNAs in metastatic TNBC exclusively via cfDNA and determine if cfDNA tumor fraction is associated with overall survival in metastatic TNBC. Patients and Methods In this retrospective cohort study, we identified 164 patients with biopsy-proven metastatic TNBC at a single tertiary care institution who received prior chemotherapy in the (neo)adjuvant or metastatic setting. We performed low-coverage genome-wide sequencing of cfDNA from plasma. Results Without prior knowledge of tumor mutations, we determined tumor fraction of cfDNA for 96.3% of patients and SCNAs for 63.9% of patients. Copy number profiles and percent genome altered were remarkably similar between metastatic and primary TNBCs. Certain SCNAs were more frequent in metastatic TNBCs relative to paired primary tumors and primary TNBCs in publicly available data sets The Cancer Genome Atlas and METABRIC, including chromosomal gains in drivers NOTCH2, AKT2, and AKT3. Prespecified cfDNA tumor fraction threshold of ≥ 10% was associated with significantly worse metastatic survival (median, 6.4 v 15.9 months) and remained significant independent of clinicopathologic factors (hazard ratio, 2.14; 95% CI, 1.4 to 3.8; P < .001). Conclusion We present the largest genomic characterization of metastatic TNBC to our knowledge, exclusively from cfDNA. Evaluation of cfDNA tumor fraction was feasible for nearly all patients, and tumor fraction ≥ 10% is associated with significantly worse survival in this large metastatic TNBC cohort. Specific SCNAs are enriched and prognostic in metastatic TNBC, with implications for metastasis, resistance, and novel therapeutic approaches.

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