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 PD-L1 expression is associated with higher residual cancer burden in triple-negative breast cancers with residual disease after neoadjuvant chemotherapy

2020 ◽  
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 ◽  
Small Subset ◽  
Breast Cancers ◽  
Residual Cancer ◽  
Cancer Burden ◽  
Residual Cancer Burden

AbstractThe 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 immune checkpoint inhibitors (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 (E1L3N clone, cutoff for positivity: ≥ 1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of surgical specimens 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 DFS (p=0.38) or OS (p=0.48), but high Ki67 levels after NAC were strongly associated with a poor prognosis (DFS 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 Evaluation of PD-L1 and tumor infiltrating lymphocytes in paired pretreatment biopsies and post neoadjuvant chemotherapy surgical specimens of breast carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lucas Grecco Hoffmann ◽  
Luis Otavio Sarian ◽  
José Vassallo ◽  
Geisilene Russano de Paiva Silva ◽  
Susana Oliveira Botelho Ramalho ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Histological Grade ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Immunohistochemical Expression ◽  
Residual Cancer Burden ◽  
Grade 3 ◽  
The Impact

AbstractHerein it was evaluated the impact of PD-L1 immunohistochemical expression and stromal tumor-infiltrating lymphocyte (sTIL) counts in pretreatment needle core biopsy on response to neoadjuvant chemotherapy (NACT) for patients with breast carcinomas (BC). In 127 paired pre- and post-NACT BC specimens, immunohistochemical expression of PD-L1 was evaluated in stroma and in neoplastic cells. In the same samples sTILs were semi-quantified in tumor stroma. Post-NACT specimens were histologically rated as having residual cancer burden (RCB of any degree), or with complete pathological response (pCR). PD-L1 expression and higher sTIL counts were associated with histological grade 3 BC. PD-L1 expression was also associated with the non-luminal-HER2+ and triple negative immunohistochemical profiles of BC. Pathological complete response was associated with histological grade 3 tumors, and with the non-luminal-HER2+ and triple negative profiles. Additionally, our results support an association between PD-L1 expression and pCR to NACT. It was also observed that there is a trend to reduction of sTIL counts in the post-NACT specimens of patients with pCR. Of note, PD-L1 was expressed in half of the hormone receptor positive cases, a finding that might expand the potential use of immune checkpoint inhibitors for BC patients.

Can MRI accurately identify which patients with operable breast cancer will have a pathologic complete response after neoadjuvant therapy?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 616-616
Author(s):  
Carolyn Nessim ◽  
Isabelle Trop ◽  
Andre Robidoux ◽  
Eleftherios P Mamounas ◽  
Jean-Francois Boileau
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Predictive Value ◽  
Triple Negative ◽  
Residual Disease ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Breast Cancers ◽  
Number Of Patients

616 Background: With the introduction of targeted therapy based on tumor subtypes, an increasing number of patients that receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR). Previous studies have shown that the accuracy of MRI is poor at predicting the response to neoadjuvant chemotherapy in locally advanced and often non-resectable breast cancers, where the rate of pCR is low. The purpose of this study is to evaluate MRI’s ability to predict a pCR in operable breast cancers after neoadjuvant therapy. Methods: All patients enrolled in the NSABP B-40, B-41, FB-5 and FB-6 protocols in a single tertiary care centre, that had an MRI done before and after neoadjuvant therapy were reviewed. A radiologist, blinded to the pathology results, interpreted the pre- and post- treatment MRI’s and made a prediction as to whether or not patients would have a pCR. In this study, a true negative was defined as a reading of a complete response on MRI that was confirmed as a pCR on final pathology. pCR was defined as having no residual invasive or in situ disease in the breast. Results: 129 women with a median age of 51 years were identified. 90% had invasive ductal carcinoma; 8% had invasive lobular. 58% were ER+, 21% were triple negative and 21% were Her2+. 16% of patients had a pCR. 25% of patients had no residual invasive cancer in the breast. pCR rates for ER+ tumors was 5%, triple negative 37%, and Her2+ 26%. 19% of patients that had a pCR had a total mastectomy. The sensitivity and specificity of MRI for predicting residual disease were 88% and 52% respectively. The positive predictive value was 90% and the negative predictive value was 46% with an accuracy of 82%. Conclusions: MRI has limited value for determining which patients had a pCR after neoadjuvant chemotherapy, even in operable breast cancers. When residual disease is suspected on MRI, it is unlikely that a pCR has been achieved. Surgical excision following neoadjuvant therapy remains the gold standard to identify which patients have achieved a pCR. Other modalities will need to be used in order to accurately determine which patients would be eligible for studies evaluating non operative management following neoadjuvant therapy.

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.

scholarly journals Prognostic Impact of Stromal Immune Infiltration before and after Neoadjuvant Chemotherapy (NAC) in Triple Negative Inflammatory Breast Cancers (TNIBC) Treated with Dose-Dense Dose-Intense NAC

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2657
Author(s):  
Luca Campedel ◽  
Paul Blanc-Durand ◽  
Asker Bin Asker ◽  
Jacqueline Lehmann-Che ◽  
Caroline Cuvier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Prognostic Impact ◽  
Breast Cancers ◽  
Dose Dense ◽  
The Impact

Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13–3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07–3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36–3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05–3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.

A meta-analysis of platinum-based neoadjuvant chemotherapy versus standard neoadjuvant chemotherapy for triple-negative breast cancer

2019 ◽  
Vol 15 (23) ◽  
pp. 2779-2790 ◽  
Author(s):  
Dong Wang ◽  
Jiafu Feng ◽  
Bei Xu
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Randomized Clinical Trials ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Complete Response ◽  
Breast Cancers ◽  
Dna Damaging Agents ◽  
Platinum Agents

Aim: Platinum agents are DNA damaging agents with promising activity in breast cancers, especially in triple-negative subgroup. This meta-analysis was conducted to compare the treatments of platinum-based neoadjuvant chemotherapy (NAC) and standard NAC for triple-negative breast cancers (TNBCs). Materials & methods: Diverse electronic databases were searched to identify the randomized clinical trials that directly compared the treatments of platinum-based NAC versus NAC in TNBC patients. Toxicity of platinum-based regimens was further evaluated. Results: Addition of platinum agents significantly improved the pathological complete response rates in TNBC patients compared with the standard NAC. Unfortunately, platinum-based regimens were more likely to develop higher incidence of hematologic toxicities. Conclusion: Platinum-based NAC regimens could achieve significant pathological complete response improvement with well-tolerated toxicity in TNBC patients.

A new measurement of residual cancer burden to predict survival after neoadjuvant chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 536-536 ◽  
Author(s):  
W. Symmans ◽  
F. Peintinger ◽  
C. Hatzis ◽  
H. Kuerer ◽  
V. Valero ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Cox Regression ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Continuous Measure ◽  
Residual Cancer ◽  
Cancer Burden ◽  
Residual Cancer Burden ◽  
Ajcc Stage

536 Background: The strength of association between tumor response and survival is critical for neoadjuvant chemotherapy trials. Pathologic complete response (pCR) reliably predicts survival benefit, but residual disease contains a range of pathologic responses that likely contain different prognostic groups, including near complete response and resistance. Methods: Pathologic slides and reports were reviewed from 432 patients in two completed neoadjuvant trials: 1) fluorouracil, doxorubicin and cyclophosphamide (FAC) in 189 patients, and 2) paclitaxel followed by FAC (T/FAC) in 243 patients. Paclitaxel was administered as twelve weekly (n=126) or four 3-weekly cycles (n=117). Residual cancer burden (RCB) was calculated as an index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We compared four RCB categories, from RCB-0 (pCR) to RCB-3 (chemoresistant), and post-treatment revised AJCC Stage (0-III) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses (stratified by ER status). Results: The pCR rate was greater after T/FAC than FAC (24% vs. 16%, LR p<0.05), and after weekly (vs. 3-weekly) paclitaxel in T/FAC (30% vs. 16%, LR p<0.01). In patients with residual disease, RCB measurements were significantly lower after T/FAC than FAC (t-test, p<0.0001), but were not different between paclitaxel schedules in T/FAC. RCB was a continuous predictor of DRFS after T/FAC (HR=1.86, 95%CI 1.51–2.30) or FAC (HR=1.67, CI 1.38–2.01) with median follow-up 5 and 8 years, respectively. The resistant category RCB-3 predicted relapse more strongly than AJCC Stage III and identified a larger group of high-risk patients ( Table ). Conclusions: RCB is a new continuous measure of pathologic response that is defined from routine pathologic materials, represents the distribution of residual disease, is a significant predictor of DRFS, and defines chemotherapy resistance more effectively than revised AJCC Stage. [Table: see text] [Table: see text]

Are BRCA1 mutations a predictive factor for anthracycline-based neoadjuvant chemotherapy response in triple-negative breast cancers?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 580-580 ◽  
Author(s):  
T. Petit ◽  
M. Wilt ◽  
J. Rodier ◽  
D. Muller ◽  
J. Ghnassia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Platinum Compounds ◽  
Response To Chemotherapy ◽  
Chemotherapy Efficacy

580 Background: BRCA1 being involved in DNA repair and apoptosis, its mutations may influence response to chemotherapy. In vitro studies demonstrated that loss of BRCA1 function increased sensitivity to platinum compounds and induced resistance to anthracyclines. BRCA1-related breast cancers tend to be ductal carcinomas with high tumor grade, absence of hormonal receptors and no HER2 overexpression, so called triple-negative. We retrospectively analyzed anthracycline-based neoadjuvant chemotherapy efficacy in triple- negative tumors according to BRCA1 status. Methods: 393 breast cancer pts were treated with FEC100 neoadjuvant chemotherapy (FU 500 mg/m2, epirubicine 100 mg/m2, cyclophosphamide 500 mg/m2) between 1/2000 and 12/2006. Out of them, 14% had a triple-negative phenotype (55 pts). Patients with young age at diagnosis or family history of breast cancer were offered genetic testing for BRCA1 and BRCA2 mutations. Twelve of these patients had a BRCA1 deleterious mutation with a triple-negative tumor. Characteristics of these 12 pts at diagnosis were: median age = 38, tumor stage = 7 T2N0, 2 T2N1, 2 T3N0, 1 T3N1. Results: Pathological complete response was defined as absence of invasive tumor in breast and axillary nodes. After 6 cycles of FEC100, 42% of patients with triple-negative tumors (23/55) had a pathological complete response, compared to 17% (2/12) with a BRCA1 mutation. Only one of the 12 BRCA1 patients had an axillary node involvement. Conclusions: In our series, BRCA1 deleterious mutations decreased anthracycline-based chemotherapy efficacy in triple- negative breast cancers. Platinum compounds should be evaluated in these BRCA1-related tumors. No significant financial relationships to disclose.

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