PD-L1 expression and TOP3A mutation as prognostic factors for adjuvant chemotherapy in triple negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 541-541
Author(s):  
Xue Wang ◽  
Peng Yuan ◽  
Feng Du ◽  
Lina Cui ◽  
Fangchao Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Functional Enrichment ◽  
Pathway Enrichment Analysis ◽  
Genetic Characteristics ◽  
Significant Difference

541 Background: Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is markedly heterogeneous and lacks specific targets. The aim of this study is to explore potential predictors and therapeutic targets based on clinical and genetic characteristics. Methods: 138 patients with triple-negative breast cancer after surgical treatment were 1:1 randomly assigned to the paclitaxel combined with carboplatin (TCb) group or the epirubicin combined with cyclophosphamide sequential paclitaxel (EC-T) adjuvant chemotherapy group. PD-L1 was retrospectively analyzed by surgically resected specimens, and 733 cancer-related genes were detected by NGS. Pathway enrichment analysis was performed using DAVID for functional enrichment genetic alterations. Cox regression models and Kaplan-Meier were used to evaluate disease-free survival (DFS). Results: In this study, there was no significant difference in DFS between the TCb and EC-T groups. 31 (22.5%) of 138 TNBC patients were positive for PD-L1 expression, including 15 (10.9%) patients positive for PD-L1 in tumor cells (TCs) and 29 (21.0%) patients positive for PD-L1 in tumor-infiltrating immune cells (TICs). Patients with positive PD-L1 expression, either in TCs or TICs, achieved better DFS [HR=0.13 (95% CI: 0.02-0.93), p=0.016], the difference was also shown in the EC-T group [HR=0 (95% CI: 0- inf), p=0.037], but not in the TCb group [HR=0 (95% CI: 0.04-2.1), p=0.189]. In addition, we identified 7 patients with mutations in DNA topoisomerase IIIα(TOP3A), a homologous recombination (HR)-related gene, and patients with mutations in this gene had worse DFS than those without mutations [HR=4]. However, there was no statistically significant association between BRCA mutation and response to either therapeutic regimens. Conclusions: In this TNBC patient population, immunohistochemistry (IHC) and NGS analyses identified potential prognostic markers. PD-L1 positive and TOP3A mutation were significantly associated with early triple-negative breast cancer prognosis.

scholarly journals Survival outcomes of neoadjuvant versus adjuvant chemotherapy in triple-negative breast cancer: a meta-analysis of 36480 cases. 

2020 ◽  
Author(s):  
Lin-Yu Xia ◽  
Qing-Lin Hu ◽  
Jing Zhang ◽  
Wei-Yun Xu ◽  
Xiao-Shi Li
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Current Evidence ◽  
Survival Outcomes ◽  
Significant Difference

Abstract Background: The survival outcomes of neoadjuvant chemotherapy (NACT) versus adjuvant chemotherapy (ACT) for patients with triple-negative breast cancer (TNBC) remain unclear. Therefore, in this study, a meta-analysis was conducted to analyze current evidence on the survival outcomes of NACT versus ACT in TNBC. Methods: A systematic search was performed on the PubMed and Embase databases to identify relevant articles investigating the survival outcomes of NACT versus ACT in TNBC. Results: A total of nine studies involving 36480 patients met the selection criteria. Among them,10728 (29.41%) received NACT, and 25752 (70.59%) received ACT. The pathological complete response (pCR) rate was 35% (95% CI = 0.23-0.48). Compared with ACT, the overall survival (OS) of NACT was poor (HR = 1.59; 95%CI = 1.25-2.02; P=0.0001), and there was no significant difference in disease-free survival (DFS) between the two treatments (HR = 0.85; 95%CI = 0.54-1.34; P=0.49). NACT with pCR significantly improved the OS (HR = 0.53; 95%CI = 0.29-0.98; P=0.04) and DFS (HR = 0.52; 95%CI = 0.29-0.94; P=0.03), while the OS (HR = 1.18; 95%CI = 1.09-1.28; P<0.0001) and DFS (HR = 2.36; 95%CI = 1.42-3.89; P=0.0008) of patients with residual disease (RD) following NACT were worse compared to those receiving ACT. Conclusion: These findings suggest that, for TNBC, NACT with pCR is superior to ACT in improving OS and DFS. and it turns to be opposite when patients receiving NACT with RD.

scholarly journals Survival outcomes of neoadjuvant versus adjuvant chemotherapy in triple-negative breast cancer: a meta-analysis in 36480 cases.

2020 ◽  
Author(s):  
Lin-Yu Xia ◽  
Qing-Lin Hu ◽  
Jing Zhang ◽  
Wei-Yun Xu ◽  
Xiao-Shi Li
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Current Evidence ◽  
Survival Outcomes ◽  
Significant Difference

Abstract Background The survival outcomes of neoadjuvant chemotherapy(NACT) versus adjuvant chemotherapy(ACT) in triple-negative breast cancer (TNBC) remains unclear. Therefore, in this study, a meta-analysis was conducted to analyze current evidence on the survival outcomes of neoadjuvant versus ACT in TNBC. Methods A systematic search of PubMed and Embase databases were done to identify relevant articles investigating the survival outcomes of NACT versus ACT in TNBC. Results A total of nine studies involving 36480 patients met the selection criteria.Of them,10728(29.41%) received NACT, and 25752(70.59%) received ACT.The pathological complete response (pCR) rate is 35% (95% CI = 0.23-0.48). Compared with ACT, the overall survival(OS) of NACT was poor(HR = 1.59; 95%CI = 1.25-2.02; P=0.0001), and there was no significant difference in disease-free survival(DFS) between them(HR = 0.85; 95%CI = 0.54-1.34; P=0.49). NACT with pCR can significantly improve the OS(HR = 0.53; 95%CI = 0.29-0.98; P=0.04) and DFS(HR = 0.52; 95%CI = 0.29-0.94; P=0.03), while the OS(HR = 1.18; 95%CI = 1.09-1.28; P<0.0001) and DFS(HR = 2.36; 95%CI = 1.42-3.89; P=0.0008) of patients with residual disease(RD) following NACT were worse compared with ACT. Conclusion The findings suggest that, for TNBC, Patients receiving NACT with pCR can significantly improve OS and DFS compared with ACT and it turns to be opposite when patients receiving NACT with RD.

ALEXANDRA/IMpassion030: A phase III study of standard adjuvant chemotherapy with or without atezolizumab in early-stage triple-negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS598-TPS598
Author(s):  
Heather L. McArthur ◽  
Michail Ignatiadis ◽  
Sebastian Guillaume ◽  
Andrew Bailey ◽  
Jorge Luis Martinez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Lymph Node Status ◽  
Phase 3 ◽  
Metastatic Setting

TPS598 Background: Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer and promising clinical activity has been reported with the anti–PD-L1 antibody, atezolizumab, in Phase 1/1b metastatic TNBC trials. Furthermore, the randomized phase 3 IMpassion130 study demonstrated enhanced anti-tumor activity when atezolizumab was co-administered with chemotherapy in the first line metastatic setting, with benefit mainly observed in PD-L1+ cohort. ALEXANDRA/IMpassion030 will evaluate the efficacy and safety of atezolizumab in combination with standard anthracycline/taxane adjuvant chemotherapy in early TNBC patients. Methods: ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard chemotherapy versus chemotherapy alone in early TNBC. In total, 2300 patients with operable stage II or III TNBC, confirmed by central pathology review, will be randomized. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant treatment will consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary end-point is invasive disease-free survival (iDFS) and secondary end-points include iDFS by PD-L1 and lymph node status, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first patient was enrolled on August 2nd 2018, and approximately 430 sites are expected to be opened globally in 30 countries. Clinical trial information: NCT03498716.

Triple Negative Breast Cancer Patients Treated with Radiation Therapy: Improvement in Survival and Local Control With Adjuvant Chemotherapy Compared To Neoadjuvant Chemotherapy – A Hypothesis Generating Report

2021 ◽  
Author(s):  
Mary Roselin Nittala ◽  
Satyaseelan Packianathan ◽  
Gary L. Shultz ◽  
Paul Roberts ◽  
Eswar K. Mundra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
African American ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
African American Women ◽  
Local Control ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival

Abstract Background Triple negative breast cancer (TNBC) (estrogen receptor (ER) – negative, progesterone receptor (PR) - negative, and human epidermal growth factor receptor 2 (HER2) -negative) is an aggressive subtype of breast cancer that is more common in younger women, carries a poorer prognosis and has a greater metastatic potential than receptor positive subtypes. Radiation therapy’s ability to improve outcomes, especially the overall survival is controversial, more so among African American patients. The objective of this study is to evaluate local control and survival rates of TNBC patients treated with radiotherapy (RT) in our institution with a sizeable cohort of African American women. Methods This is a retrospective analysis of 67 TNBCs (2007–2017) at an academic state institution who underwent a lumpectomy and /or mastectomy (surgery) followed by adjuvant irradiation to a median total dose of 50 Gy (range 40.5–50.40 Gy). Chemotherapy was administered in a neoadjuvant (32) or adjuvant setting (35). For all 67 TNBCs, local control (LC), overall survival (OS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method. The significance of survival variables was analyzed using the Cox univariate and multivariate proportional hazards model. A p-value of less than 0.05 was considered statistically significant. The SPSS 24.0 software was used for data analysis. Results The baseline characteristics of all 67 TNBCs were measured with median follow up of 58 months (range 10–142 months). Patients were stratified into two groups (neoadjuvant chemotherapy-RT (32) vs. adjuvant chemotherapy-RT (35)). The five-year rates for LC, DFS and OS were 14.8 % vs. 47.9 % (p = 0.002), 24.2% vs. 53.1 % (p = 0.015), and 65.1% vs. 92.2% (0.002) respectively. On Cox multivariate analysis, patients who received adjuvant chemotherapy were associated with statistically improved significant LC (p = 0.002) and OS (p = 0.002). The variables included were: BMI (p = 0.050), distance travelled (p = 0.027), 8th AJCC TNM staging (p = 0.018) and tumor grade (p = 0.022). Conclusion In this hypothesis-generating report, among TNBC patients undergoing RT, adjuvant chemotherapy appears to be better than neoadjuvant chemotherapy in determining the clinical outcomes.

scholarly journals Survival Outcome and Impact of Chemotherapy in T1 Node-Negative Triple-Negative Breast Cancer: A SEER Database Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jingyi Zhang ◽  
Wenna Wang ◽  
Jiayu Wang ◽  
Yang Luo ◽  
Shanshan Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Large Scale ◽  
Triple Negative ◽  
Survival Rates ◽  
Seer Database ◽  
Cancer Specific Survival ◽  
Small Tumor ◽  
Significant Difference

Objective. Although triple-negative breast cancer (TNBC) has been considered to be an aggressive disease, the outcome of small-tumor (T1abcN0M0) TNBC and the effect of adjuvant chemotherapy on TNBC survival remain controversial. Methods. We identified 4565 T1abcN0M0 TNBC patients in the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2015. After propensity score matching (PSM), 3214 patients were finally analyzed. Survival rates were compared among T1a, T1b, and T1c patients and between patients with and without adjuvant chemotherapy. Results. We classified 424, 1040, and 3101 cases as T1a, T1b, and T1c TNBC, respectively. A total of 2760 (60.5%) patients received adjuvant chemotherapy, accounting for 25.5%, 56.0%, and 66.8% of T1a, T1b, and T1c patients, respectively. Rates of 5-year breast cancer-specific survival (BCSS) for T1a, T1b, and T1c patients receiving chemotherapy were 97.8%, 94.1%, and 94.5%, respectively, compared with 97.2%, 94.0%, and 89.9% in patients without chemotherapy. Patients receiving adjuvant chemotherapy had higher 5-year BCSS (94.5% vs. 89.9%, P  = 0.004) in the T1c subgroup, but no significant difference was detected in T1a or T1b patients due to adjuvant chemotherapy. Conclusion. Small-tumor TNBC showed very good prognosis. Adjuvant chemotherapy improved prognosis in T1c TNBC cases to a greater extent than in T1a and T1b patients. More large-scale clinical trials are needed, and further study should be conducted to determine appropriate adjuvant chemotherapy for T1c TNBC patients.

scholarly journals Impact of estrogen receptor levels on outcome in non-metastatic triple negative breast cancer patients treated with neoadjuvant/adjuvant chemotherapy

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maria Vittoria Dieci ◽  
Gaia Griguolo ◽  
Michele Bottosso ◽  
Vassilena Tsvetkova ◽  
Carlo Alberto Giorgi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Adjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Neo Adjuvant Chemotherapy

AbstractAlthough 1% is the recommended cut-off to define estrogen receptor (ER) positivity, a 10% cut-off is often used in clinical practice for therapeutic purposes. We here evaluate clinical outcomes according to ER levels in a monoinstitutional cohort of non-metastatic triple-negative breast cancer (BC) patients undergoing (neo)adjuvant chemotherapy. Clinicopathological data of 406 patients with ER < 10% HER2-negative BC treated with (neo)adjuvant chemotherapy between 01/2000 and 04/2019 were collected. Patients were categorized in ER-negative (ER < 1%; N = 364) and ER-low positive (1–9%, N = 42). At a median follow-up of 54 months, 88 patients had relapsed and 64 died. No significant difference was observed in invasive relapse-free survival (iRFS) and overall survival (OS) according to ER expression levels, both at univariate and multivariate analysis (5-years iRFS 74.0% versus 73.1% for ER-negative and ER-low positive BC, respectively, p = 0.6; 5-years OS 82.3% versus 76.7% for ER-negative and ER-low positive BC, respectively, p = 0.8). Among the 165 patients that received neoadjuvant chemotherapy, pathological complete response rate was similar in the two cohorts (38% in ER-negative, 44% in ER-low positive, p = 0.498). In conclusion, primary BC with ER1–9% shows similar clinical behavior to ER 1% BC. Our results suggest the use of a 10% cut-off, rather than <1%, to define triple-negative BC.

ALEXANDRA/IMpassion030: A phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in patients with early-stage triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS597-TPS597
Author(s):  
Shigehira Saji ◽  
Heather L. McArthur ◽  
Michail Ignatiadis ◽  
Andrew Bailey ◽  
Sarra El-Abed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Phase 3 ◽  
Meaningful Improvement

TPS597 Background: Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting, it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer. Atezolizumab (an anti–PD-L1 antibody), in combination with nab-paclitaxel has been approved in >70 countries for the treatment of PD-L1-positive unresectable locally advanced or metastatic TNBC based on the results of the randomized phase 3 IMpassion130 trial. The phase 3 IMpassion031 study, evaluating atezolizumab in combination with chemotherapy (nab-paclitaxel followed by doxorubicin and cyclophosphamide) in comparison to placebo plus chemotherapy as neoadjuvant treatment demonstrated a statistically significant and clinically meaningful improvement in pCR in both PD-L1 positive and PD-L1 negative tumors. ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial currently investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard anthracycline/taxane adjuvant chemotherapy versus chemotherapy alone in early stage TNBC. Methods: ALEXANDRA/IMpassion030 will randomize 2300 patients with operable stage II-III TNBC, confirmed by central pathology review. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant chemotherapy consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary endpoint is invasive disease-free survival (iDFS) and secondary endpoints include, iDFS in the PD-L1 selected tumour status (IC1/2/3) and node-positive subpopulations, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first site was activated on May 4 2018, and approximately 373 sites in 30 countries are currently participating in this trial. This trial is sponsored by F. Hoffmann-La Roche Ltd and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials. Clinical trial information: NCT03498716.

Tumor-infiltrating lymphocytes to predict survival to anthracycline/taxane-based adjuvant chemotherapy in triple negative breast cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 1-1
Author(s):  
Qiyun Ou ◽  
Yunfang Yu ◽  
Xiaoyun Xiao ◽  
Baoming Luo
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Breast Cancer Subtypes ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Infiltrating Lymphocytes

1 Background: Previous clinical data suggested that the tumour-infiltrating lymphocytes (TILs) were predictive in breast cancer treated with adjuvant chemotherapy; however, clinical relevance has yet to be established. We hypothesized that TILs would be associated with overall survival (OS) and disease-free survival (DFS) after anthracycline/taxane-based adjuvant chemotherapy in breast cancer subtypes. Methods: PubMed and EMBASE were searched until March 2017 for studies that investigated the association of TILs with survival for anthracycline/taxane-based adjuvant chemotherapy in breast cancer. OS and DFS were combined using random-effects meta-analysis and calculated as combined hazard ratio (HR) with 95% credible intervals (CIs). The PROSPERO registry number is CRD42017072133. Results: Twelve studies comprising 9,023 patients were eligible for analysis. Six were prospective adjuvant trials (n = 7686) and six were retrospective studies (n = 1337). Pooled analysis indicated that high TILs have no significant predictive association in overall population (DFS, HR = 0.87, 95% CI, 0.70 – 1.08; OS, HR = 0.98, 95% CI, 0.89 – 1.07), Luminal A/B (DFS, HR = 0.99, 95% CI, 0.94 – 1.04; OS, HR = 1.01, 95% CI, 0.92 – 1.12), and HER2–positive patients (DFS, HR = 0.84, 95% CI, 0.71 – 1.00; OS, HR = 0.89, 95% CI, 0.77 – 1.02), but were related to improved DFS (HR, 0.81; 95% CI, 0.73 – 0.89) and OS (HR, 0.74; 95% CI, 0.66 – 0.84) in triple negative breast cancer (TNBC) patients. Additionally, increasing TILs were not significantly associated with reduced risk of relapse in HER2-positive patient through adjuvant trastuzumab (HR, 0.97; 95% CI, 0.93 – 1.01). Conclusions: This meta-analysis provides an evidence that TILs predicts survival to anthracycline/taxane-based adjuvant chemotherapy in TNBC patients and suggests that predictive benefit seemed to be influenced by breast cancer subtypes as well.

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