Abstract OT3-01-02: PARTNERING / PARTNER : Phase II sub-study to establish if the addition of combinations of new agents (olaparib, cell cycle and immune checkpoint inhibitors) can improve the rate of pathological complete response (pCR) and minimal residual disease (MRD) in triple negative breast cancer (TNBC) and / or germline BRCA mutated (gBRCAm) patients with evidence of residual disease after PARTNER therapy

2019 ◽  
Author(s):  
JE Abraham ◽  
A-L Vallier ◽  
W Qian ◽  
A Machin ◽  
L Grybowicz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Immune Checkpoint Inhibitors ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
New Agents ◽  
Minimal Residual

scholarly journals PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 746
Author(s):  
Beatriz Grandal ◽  
Manon Mangiardi-Veltin ◽  
Enora Laas ◽  
Marick Laé ◽  
Didier Meseure ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Rapid Development ◽  
Complete Response ◽  
Tumor Burden ◽  
Small Subset ◽  
Breast Cancers ◽  
Residual Cancer Burden

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors’ (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p = 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC, p = 0.25, and PD-L1-IC, p = 0.95) or overall survival (OS) (PD-L1-TC, p = 0.48, and PD-L1-IC, p = 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS, p = 0.0014, and OS, p = 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.

scholarly journals Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

2017 ◽  
Vol 63 (3) ◽  
pp. 691-699 ◽  
Author(s):  
Francesca Riva ◽  
Francois-Clement Bidard ◽  
Alexandre Houy ◽  
Adrien Saliou ◽  
Jordan Madic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Minimal Residual Disease ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Tp53 Mutations ◽  
Tumor Dna ◽  
Minimal Residual

Abstract BACKGROUND In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery. METHODS Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 (TP53) mutations previously characterized in tumor tissue by massively parallel sequencing (MPS). RESULTS Forty-six patients with nonmetastatic TNBC were enrolled. TP53 mutations were identified in 40 of them. Customized ddPCR probes were validated for 38 patients, with excellent correlation with MPS (r = 0.99), specificity (≥2 droplets/assay), and sensitivity (at least 0.1%). At baseline, ctDNA was detected in 27/36 patients (75%). Its detection was associated with mitotic index (P = 0.003), tumor grade (P = 0.003), and stage (P = 0.03). During treatment, we observed a drop of ctDNA levels in all patients but 1. No patient had detectable ctDNA after surgery. The patient with rising ctDNA levels experienced tumor progression during NCT. Pathological complete response (16/38 patients) was not correlated with ctDNA detection at any time point. ctDNA positivity after 1 cycle of NCT was correlated with shorter disease-free (P < 0.001) and overall (P = 0.006) survival. CONCLUSIONS Customized ctDNA detection by ddPCR achieved a 75% detection rate at baseline. During NCT, ctDNA levels decreased quickly and minimal residual disease was not detected after surgery. However, a slow decrease of ctDNA level during NCT was strongly associated with shorter survival.

scholarly journals Immunotherapy in Breast Cancer: When, How, and What Challenges?

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1687
Author(s):  
Beatriz Henriques ◽  
Fernando Mendes ◽  
Diana Martins
Keyword(s):  
Breast Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Disease Recurrence ◽  
Resistance Mechanisms ◽  
Trastuzumab Emtansine ◽  
Drug Conjugates ◽  
Therapy Strategy ◽  
Extrinsic Resistance

Breast Cancer (BC) is the second most frequent cause of cancer death among women worldwide and, although there have been significant advances in BC therapies, a significant percentage of patients develop metastasis and disease recurrence. Since BC was demonstrated to be an immunogenic tumor, immunotherapy has broken through as a significant therapy strategy against BC. Over the years, immunotherapy has improved the survival rate of HER2+ BC patients due to the approval of some monoclonal antibodies (mAbs) such as Trastuzumab, Pertuzumab and, recently, Margetuximab, along with the antibody-drug conjugates (ADC) Trastuzumab-Emtansine (T-DM1) and Trastuzumab Deruxtecan. Immune checkpoint inhibitors (ICI) showed promising efficacy in triple-negative breast cancer (TNBC) treatment, namely Atezolizumab and Pembrolizumab. Despite the success of immunotherapy, some patients do not respond to immunotherapy or those who respond to the treatment relapse or progress. The main causes of these adverse events are the complex, intrinsic or extrinsic resistance mechanisms. In this review, we address the different immunotherapy approaches approved for BC and some of the mechanisms responsible for resistance to immunotherapy.

Combination of individual tumor gene expression profiles and quantitative ultrasound and mammography imaging to understand the response to neoadjuvant chemotherapy among Hispanic-Latina women with early stages of triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12605-e12605
Author(s):  
Alexander Philipovskiy ◽  
Sumit Gaur ◽  
Karen Chambers ◽  
Roberto Gamez ◽  
Renato Aguilera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Tumor Response ◽  
Residual Disease ◽  
Complete Response ◽  
Response To Chemotherapy ◽  
Before And After ◽  
The Individual

e12605 Background: Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer (BC) characterized by the absence of targetable receptors. Traditionally, neoadjuvant chemotherapy (NACT) has been used to downstage the tumors and increase the chance for breast-conserving surgery. The pathological complete response (pCR) has been traditionally considering the best predictive marker for the disease recurrence. Patients with residual disease (RD) have a poor prognosis with a high risk of recurrence, and therefore additional chemotherapy was recommended. Therefore it is an important task for clinical researchers to identify markers to predict the individual tumor response to chemotherapy and avoid in patients potentially resistant tumors. Instead, a surgical approach can be used or combined approach with chemotherapy and immunotherapy. It is not clear yet which approach is optimal for those patients with chemotherapy-resistant tumors since there is no clinical data available and no clinical tool that helps predict the individual tumor response. In this study, we examined breast ultrasound(US) images of patients before and after the completion of NACT and correlated with response to chemotherapy. To better understand the biology of resistance to chemotherapy, we also analyzed the gene expression profile of 15 patients with RD after NACT. Methods: In this study, we retrospective analyzed breast US data from 37 Hispanic patients diagnosed with TNBC and treated with NACT. Patients underwent breast US before and after NACT with documentation of clinical complete response (cCR) or clinical residual disease (cRD). Post-operatively, the pathologic response was defined as the absence of tumor cells (pCR) or presence of residual invasive tumor (RD). A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR. Also, we analyzed formalin-fixed paraffin-embedded tumor samples from 15 patients with RD after NACT. Results: Seventeen patients (45.9%) achieved pCR, and twenty (54.1%) had RD after NACT. The most common US findings connected with RD was the deposition of calcium before NACT six (30%) patients. Gene expression analysis of RD samples identified 446 upregulated and 275 downregulated genes. Among commonly upregulated genes related to cancer, we identified GLI1, IGF1, SERPINE1, ATF3, KLK 5; 7, and TUBB2b, and genes belonging to pathways encoding extracellular matrix–related proteins, DNA-damage response proteins, and pathways related to resistance to chemotherapeutic agents such as Taxol. Conclusions: Our data suggested that gene expression profiling in combination with imaging study can be used to identify patients with TNBC potentially resistant to chemotherapy.

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