scholarly journals Epithelial/Mesenchymal Characteristics and PD-L1 Co-Expression in CTCs of Metastatic Breast Cancer Patients Treated with Eribulin: Correlation with Clinical Outcome

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3735
Author(s):  
Hara Polioudaki ◽  
Anastasia Mala ◽  
Eleni Gkimprixi ◽  
Maria A. Papadaki ◽  
Amanda Chantziou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Mononuclear Cells ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Increased Risk

We aimed to evaluate the co-expression of PD-L1 and epithelial-mesenchymal markers in CTCs from metastatic breast cancer (MBC) patients and to determine if there is any relationship with patients’ outcome after eribulin treatment. Using cytospin preparations of peripheral blood mononuclear cells (PBMCs) from MBC patients treated with eribulin and a combination of immunocytochemistry and immunofluorescence, we quantified PD-L1, keratins and vimentin in single and cluster CTCs on days 1 and 8 of the first-treatment cycle. CTCs (n = 173) were found in 31 out of 38 patients. At baseline, the presence of cluster CTCs (p = 0.048), cluster mesenchymal CTCs (mCTCs) (p = 0.0003) or cluster PD-L1+mCTCs (p = 0.006) was associated with shorter overall survival (OS). In multivariate cox regression analysis, the detection of cluster mCTCs was the only parameter associated with increased risk of death (p = 0.024). On day 8 post-eribulin administration, PD-L1+mCTCs and especially single PD-L1+mCTCs decreased in 75% and 89% of patients, respectively. The detection of single PD-L1+mCTCs after eribulin treatment was correlated with shorter PFS (p = 0.047) and OS (p = 0.020). In conclusion, our study identified for the first time that cluster and single PD-L1+mCTCs subpopulations are of clinical significance in patients with MBC and highlighted the importance of CTC phenotyping during treatment with eribulin.

Immunoglobulin G fragment C receptor polymorphisms and response to trastuzumab-based treatment in patients with HER-2/neu-positive metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13090-13090 ◽  
Author(s):  
A. Musolino ◽  
N. Naldi ◽  
B. Bortesi ◽  
M. Capelletti ◽  
D. Pezzuolo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Immunoglobulin G ◽  
Mononuclear Cells ◽  
Metastatic Breast ◽  
Cancer Cell Line ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Immune Effector ◽  
Her 2

13090 Background: A potential mechanism of action of the humanized anti-HER-2/neu monoclonal antibody Trastuzumab involves antibody-dependent cellular cytotoxicity (ADCC) with the activation of immune effector cells via their immunoglobulin G fragment C receptors (FcγRs). Trastuzumab has been shown to engage both activation (FcγRIIIa; FcγRIIa) and inhibitory (FcγRIIb) antibody receptors on myeloid cells and several FcγR polymorphisms have been identified that may affect the antibody-dependent cytotoxicity of natural killer cells and macrophages. Methods: Forty consecutive HER-2/neu-positive (FISH+) metastatic breast cancer patients receiving a trastuzumab-based treatment (combined with paclitaxel for the majority) were examined for the FcγRIIIa 158 valine (V)/phenylalanine (F), FcγRIIa 131 histidine (H)/arginine (R), and FcγRIIb 232 isoleucine (I)/threonine (T) polymorphisms. A PCR-RFLP based assay using genomic DNA was performed for FcγRIIIa and FcγRIIa genotyping, while PCR-SSCP methods using complementary DNA were utilized for FcγRIIb. Patients’ peripheral blood mononuclear cells were drawn before treatment initiation and their trastuzumab-mediated killing function was measured by 51Cr release using a HER-2/neu-expressing human breast cancer cell line as a target. The results were then correlated with clinical outcome of these patients. Results: Median age was 60 years (range 26–83 years). Thirty-six (90%) patients received a trastuzumab-based treatment as first-line therapy. The overall clinical benefit rate (CR+PR+SD) was 65% (95% Confidence Interval: 62–71%), including 8 (20%) complete and 11 (27.5%) partial responses. Median survival was 22.3 mo with a median PFS of 7 mo. Trastuzumab-based treatment was well tolerated and no changes in cardiac function were observed. Conclusions: This study evaluates for the first time the potential role of FcγR polymorphisms in predicting response to trastuzumab-based treatment. Results according to this study purpose will be presented at the meeting. No significant financial relationships to disclose.

Breast Cancer With Synchronous Metastases: Trends in Survival During a 14-Year Period

2004 ◽  
Vol 22 (16) ◽  
pp. 3302-3308 ◽  
Author(s):  
Fabrice Andre ◽  
Khemaies Slimane ◽  
Thomas Bachelot ◽  
Arianne Dunant ◽  
Moise Namer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Metastatic Breast ◽  
New Drugs ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Cox Regression Analysis ◽  
Over Time

Purpose Although new drugs were approved during the 1990s for the treatment of metastatic breast cancer, it is not clear whether their use has changed the outcome of patients in daily practice. This study sought to determine whether survival has improved over time for breast cancer patients who had metastases at diagnosis. Patients and Methods A total of 724 patients have been treated in three French cancer centers for an initially metastatic breast cancer between 1987 and 2000; 343 were diagnosed between 1987 and 1993, and 381 were diagnosed between 1994 and 2000. Tumor characteristics, treatments, and outcomes of these patients were compared by χ2 test, log-rank test, and Cox regression analysis. Results Characteristics were not different between the patients diagnosed from 1987 to 1993 and those diagnosed from 1994 to 2000. Ten percent of patients treated from 1987 to 1994 and 58% of patients treated from 1994 to 2000 have received either a taxane or a new aromatase inhibitor. The 3-year overall survival rates were 27% for patients treated from 1987 to 1993 and 44% for patients treated from 1994 to 2000 (P < .001). The treatment period (1994 to 2000 v 1987 to 1993) was a prognostic factor in multivariate analysis (relative risk, 0.6; P < .001). Conclusion The survival of breast cancer patients presenting with metastases at diagnosis has improved over time. This study strongly suggests that this improvement is related to treatment.

scholarly journals Increased risk of SSEs in bone-only metastatic breast cancer patients treated with zoledronic acid

2017 ◽  
Vol 8 ◽  
pp. 18-22 ◽  
Author(s):  
Masashi Yanae ◽  
Shinichiro Fujimoto ◽  
Kaori Tane ◽  
Maki Tanioka ◽  
Kimiko Fujiwara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Zoledronic Acid ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Increased Risk

scholarly journals Survival impact of primary tumor resection in de novo metastatic breast cancer patients (GEICAM/El Alamo Registry)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sara Lopez-Tarruella ◽  
M. J. Escudero ◽  
Marina Pollan ◽  
Miguel Martín ◽  
Carlos Jara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Cox Regression ◽  
De Novo ◽  
Histological Grade ◽  
Tumor Resection ◽  
Metastatic Breast ◽  
Breast Cancer Patients

AbstractThe debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. We explored this approach’s outcomes in patients included in a retrospective registry, named El Álamo, of breast cancer patients diagnosed in Spain (1990–2001). In this analysis we only included de novo MBC patients, 1415 of whom met the study’s criteria. Descriptive, Kaplan-Meier and Cox regression analyses were carried out. Median age was 63.1 years, 49.2% of patients had single-organ metastasis (skin/soft tissue [16.3%], bone [33.8%], or viscera [48.3%]). PT surgery (S) was performed in 44.5% of the cases. S-group patients were younger, had smaller tumors, higher prevalence of bone and oligometastatic disease, and lower prevalence of visceral involvement. With a median follow-up of 23.3 months, overall survival (OS) was 39.6 versus 22.4 months (HR = 0.59, p < 0.0001) in the S- and non-S groups, respectively. The S-group OS benefit remained statistically and clinically significant regardless of metastatic location, histological type, histological grade, hormone receptor status and tumor size. PT surgery (versus no surgery) was associated with an OS benefit suggesting that loco-regional PT control may be considered in selected MBC patients. Data from randomized controlled trials are of utmost importance to confirm these results.

scholarly journals Exploratory analysis of circulating cytokines in patients with metastatic breast cancer treated with eribulin: the TRANSERI-GONO (Gruppo Oncologico del Nord Ovest) study

ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e000876 ◽  
Author(s):  
Ornella Garrone ◽  
Andrea Michelotti ◽  
Matteo Paccagnella ◽  
Filippo Montemurro ◽  
Anna Maria Vandone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Tumour Microenvironment ◽  
Exploratory Analysis ◽  
Cox Regression Analysis ◽  
Circulating Cytokines

BackgroundAnticancer drugs can interact with the tumour microenvironment and their effects could be exploited to favour anticancer immune response. Eribulin contributes to tumour vasculature remodelling and transforming growth factor β (TGF-β) modulation in experimental models and in humans. We performed a prospective, translational, exploratory analysis of the levels of circulating cytokines at different time points in patients with metastatic breast cancer treated with eribulin.MethodsTGF-β, tumour necrosis factor α, vascular endothelial growth factor, IL-6, IL-8, IL-10, IL-21 and C-C motif chemokine ligand-2 levels were assessed in peripheral blood samples obtained from seven healthy volunteers and 41 patients at baseline (T0), after four cycles of eribulin (T1) and at disease progression (TPD). Baseline values and longitudinal changes in cytokine levels were then related to clinical outcome.ResultsIn the 41 patients, high IL-6 and IL-8 (above the median) at T0 significantly correlated with worse survival. At T1, IL-21 significantly decreased in patients with TPD within the fourth course of treatment, compared with patients without progression. TGF-β and IL-8 above the median and IL-21 below the median at T1 significantly correlates with worse progression free survival (PFS). Patients exhibiting an increase of TGF-β or a decline of IL-21 between T0 and T1 showed a significantly worse PFS. Multivariate Cox regression analysis showed that only plasma TGF-β changes at T1 correlated with survival. At TPD, TGF-β significantly increased in all patients.ConclusionsWe observed a significant correlation between TGF-β decline during eribulin treatment and outcome in patients with metastatic breast cancer. Altogether, our data suggest that eribulin treatment might interfere with the tumour microenvironment.

scholarly journals FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients

2020 ◽  
Vol 12 ◽  
pp. 175883592091530
Author(s):  
Ning Xie ◽  
Can Tian ◽  
Hui Wu ◽  
Xiaohong Yang ◽  
Liping liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Poor Prognosis ◽  
Significant Risk ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Genetic Aberrations ◽  
Increased Risk

Background: The survival status of patients with breast cancer and brain metastasis (BCBM) receiving current treatments is poor. Method: We designed a real-world study to investigate using patients’ clinical and genetic aberrations to forecast the prognoses of BCBM patients. We recruited 146 BCBM patients and analyzed their clinical features to evaluate the overall survival (OS). For genetic testing, 30 BCBM and 165 non-brain-metastatic (BM) metastatic breast cancer (MBC) patients from Hunan Cancer Hospital, and 86 BCBM and 1416 non-BM MBC patients from the Geneplus database who received circulating tumor DNA testing, were compared and analyzed. Results: Ki67 >14% and >3 metastatic brain tumors were significant risk factors associated with poor OS, while chemotherapy and brain radiotherapy were beneficial factors for better OS. Compared with non-BM MBC patients, BCBM patients had more fibroblast growth factor receptor ( FGFR) aberrations. The combination of FGFR, TP53 and FLT1 aberrations plus immunohistochemistry HER2-positive were associated with an increased risk of brain metastasis (AUC = 77.13%). FGFR aberration alone was not only a predictive factor (AUC = 67.90%), but also a significant risk factor for poor progression-free survival (Logrank p = 0.029). FGFR1 aberration was more frequent than other FGFR family genes in BCBM patients, and FGFR1 aberration was significantly higher in BCBM patients than non-BM MBC patients. Most FGFR1-amplified MBC patients progressed within 3 months of the late-line (>2 lines) treatment. Conclusion: A group of genetic events, including FGFR, TP53 and FLT1 genetic aberrations, and HER2-positivity, forecasted the occurrence of BM in breast cancers. FGFR genetic aberration alone predicted poor prognosis.

Correlation between NK function and response to trastuzumab in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3036-3036
Author(s):  
A. Beano ◽  
E. Signorino ◽  
M. A. Polimeni ◽  
M. Mistrangelo ◽  
M. Ardine ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nk Cells ◽  
Disease Progression ◽  
Mononuclear Cells ◽  
Metastatic Breast ◽  
Nk Activity ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Peripheral Blood Mononuclear ◽  
Effector Cells

3036 Background: Trastuzumab is a monoclonal antibody selectively directed against Her2 approved for the treatment of Her2 overexpressing breast cancer patients. Its proposed mechanisms of action include also a role in mediating antibody-dependent cellular cytotoxicity (ADCC), through the triggering of the FcγRIII on natural killer (NK) cells. This study addressed the correlation between overall NK function and clinical trastuzumab activity. Methods: Between March and September 2006 22 metastatic patients in treatment with trastuzumab alone (8 mg/kg load and then 6 mg/kg every 3 weeks until disease progression) as maintaining therapy after chemotherapy were analyzed for clinical and immunological responses. According to RECIST criteria, 14 patients obtained a response to trastuzumab, while 8 patients had a disease progression. Patient’s peripheral blood mononuclear cells were tested for cytotoxic activity against standard NK target (the MHC class I-negative K562 cell line) and trastuzumab-coated MCF7 (Her2-negative) and SKBR3 (Her2-positive) human cell lines in a 4-h 51Cr-release cytotoxicity assay in the presence of grading concentrations of effector cells. Results: NK activity was significantly (p<0.05) higher in responder compared to non responder patients at all the four effector:target (50:1 to 6:1) ratios tested. NK activity of non responder patients was significantly lower than that of 25 sex and age matched controls (p<0.02) and this was not merely due to chemotherapy- or tumor-associated immunosuppression, since the values of responder patients did not significantly differ from those of controls. ADCC activity against Her2-positive SKBR3 cells was also significantly higher in responder compared to non responder patients (p<0.05) and markedly so when compared to controls (p<0.001). Conclusions: The fact that, as shown here, normal levels of FcγR- independent and higher than normal levels of FcγR-dependent cytotoxicity are required for trastuzumab response, lends support to a paramount role of NK cells in the mechanism of action of this drug. No significant financial relationships to disclose.

Survival length differences in non-metastatic breast cancer patients with different chemo-radiation time intervals.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12096-e12096
Author(s):  
Ruaa Al-Ward ◽  
Wajdi Al Shweiat ◽  
Talasila Lakshmi ◽  
Sandeep Singh Grewal ◽  
Perla Subbaiah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Survival Duration ◽  
P Value ◽  
Breast Cancer Patients ◽  
Time Intervals ◽  
Cox Regression Analysis

e12096 Background: Chemotherapy-radiotherapy time intervals (CRTI) in breast cancer vary based on recovery from chemotherapy side effects and preferences of physicians and patients. Our study aimed to determine the association of the time-interval between chemotherapy and radiation with prognosis (recurrence and survival duration) in non-metastatic breast cancer patients (stages I-III). Methods: We included female patients from Karmanos Cancer Center (KCC) database > 21 years, diagnosed with non-metastatic breast cancer from 2005-2015, who underwent surgery, chemotherapy and radiation. CRTI was divided into <24, 24-30 and >30 weeks. Cox regression analysis using age, race, stage, grade, ER/PR status and CRTI variables was done to determine the independent predictors of prognosis. Kaplan-Meier survival curves were used to demonstrate differences in survival time of CRTI groups. Results: We included 553 patients, majority were Caucasian (460 [83.5%]) with a mean age of 57.0 years (SD 11.9). Patients in the >30 weeks CRTI group were more likely to have stage III breast carcinoma when compared to <24 and 24-30 weeks groups (45.0% vs.12.4% vs. 27.8%, p-value <0.001). There were no significant differences in the local and distant recurrence rates among the 3 groups. Patients in <24 weeks CRTI group had a greater mean survival (118.7 vs. 109.2 vs.100.9 months; p-value 0.016) when compared to 24-30 and >30 weeks groups. Only clinical stage (stage 3 vs. 1 HR 3.60; 95% CI 1.89-7.02) and ER/PR status (negative vs. positive HR 1.74; 95% CI 1.02-2.94) were independent predictors of overall survival in multivariate analysis. CRTI was not significantly associated with survival in multivariate analysis (<24 weeks ref, 24-30 weeks HR 1.09; 95% CI 0.59-1.93, >30 weeks HR 1.48; 95% CI 0.82-2.59). However, patients in >30 weeks group were at greater risk of dying when compared to <24 weeks, even after controlling for stage. Conclusions: Our study showed a trend towards a worse outcome in patients with longer chemo-radiation interval, despite controlling for other variables in the multivariate analysis. The conclusions of this single center study need to be verified by further studies with larger sample size.

scholarly journals The prognostic value of androgen receptor (AR) in HER2-enriched metastatic breast cancer

2020 ◽  
Vol 27 (4) ◽  
pp. 199-208 ◽  
Author(s):  
Xinyue Wang ◽  
Xiwen Bi ◽  
Zhangzan Huang ◽  
Jiajia Huang ◽  
Wen Xia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Metastatic Breast Cancer ◽  
Androgen Receptor ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Independent Prognostic Factor ◽  
First Line ◽  
Cox Regression Analysis

The significance of androgen receptor (AR) in metastatic breast cancer (MBC) remains unclear, and it is still largely unknown how AR expression level influences HER2-positive tumors. This study aimed to investigate the prognostic and predictive value of AR in HER2-enriched MBC. Primary and/or paired metastatic tumors of 304 patients with pathologically confirmed HER2-enriched MBC were collected and immunohistochemically assessed for AR expression. The associations of AR and other clinicopathological characteristics were compared using the Chi-square test. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method and log-rank test. Cox regression analysis was used to determine independent prognostic factors. AR-positivity with a cut-off value of 10% was observed in 237 (78.0%) cases and was associated with longer PFS, 13.2 months, as compared to that of 8.2 months (P = 0.004) in patients with AR-negativity. Moreover, a significant increase in the 5-year OS rate (65.3% vs 36.2%, P < 0.001) was also observed for patients with AR-positive tumors. Cox regression analysis identified AR-positivity as an independent prognostic factor of both PFS (hazard ratio = 0.71, P = 0.039) and OS (HR = 0.53, P = 0.013). Additionally, for those who received first-line Trastuzumab therapies, prolonged PFS (15.8 months vs 8.2 months, P = 0.005) and 5-year OS rate (66.2% vs 26.2%, P = 0.009) were observed in AR-positive tumors compared to AR-negative ones. In conclusion, AR was identified as an independent prognostic factor for favorable PFS and OS and could also predict the efficacy of first-line Trastuzumab treatment in patients with HER2-enriched MBC.

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