scholarly journals Multiplex immunofluorescence to measure dynamic changes in tumor-infiltrating lymphocytes and PD-L1 in early-stage breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Katherine Sanchez ◽  
Isaac Kim ◽  
Brie Chun ◽  
Joanna Pucilowska ◽  
William L. Redmond ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hierarchical Linear Modeling ◽  
Immune Cell ◽  
Early Stage ◽  
Post Treatment ◽  
Early Stage Breast Cancer ◽  
Linear Modeling ◽  
Dynamic Changes ◽  
Efficient Detection ◽  
The Impact

Abstract Background The H&E stromal tumor-infiltrating lymphocyte (sTIL) score and programmed death ligand 1 (PD-L1) SP142 immunohistochemistry assay are prognostic and predictive in early-stage breast cancer, but are operator-dependent and may have insufficient precision to characterize dynamic changes in sTILs/PD-L1 in the context of clinical research. We illustrate how multiplex immunofluorescence (mIF) combined with statistical modeling can be used to precisely estimate dynamic changes in sTIL score, PD-L1 expression, and other immune variables from a single paraffin-embedded slide, thus enabling comprehensive characterization of activity of novel immunotherapy agents. Methods Serial tissue was obtained from a recent clinical trial evaluating loco-regional cytokine delivery as a strategy to promote immune cell infiltration and activation in breast tumors. Pre-treatment biopsies and post-treatment tumor resections were analyzed by mIF (PerkinElmer Vectra) using an antibody panel that characterized tumor cells (cytokeratin-positive), immune cells (CD3, CD8, CD163, FoxP3), and PD-L1 expression. mIF estimates of sTIL score and PD-L1 expression were compared to the H&E/SP142 clinical assays. Hierarchical linear modeling was utilized to compare pre- and post-treatment immune cell expression, account for correlation of time-dependent measurement, variation across high-powered magnification views within each subject, and variation between subjects. Simulation methods (Monte Carlo, bootstrapping) were used to evaluate the impact of model and tissue sample size on statistical power. Results mIF estimates of sTIL and PD-L1 expression were strongly correlated with their respective clinical assays (p < .001). Hierarchical linear modeling resulted in more precise estimates of treatment-related increases in sTIL, PD-L1, and other metrics such as CD8+ tumor nest infiltration. Statistical precision was dependent on adequate tissue sampling, with at least 15 high-powered fields recommended per specimen. Compared to conventional t-testing of means, hierarchical linear modeling was associated with substantial reductions in enrollment size required (n = 25➔n = 13) to detect the observed increases in sTIL/PD-L1. Conclusion mIF is useful for quantifying treatment-related dynamic changes in sTILs/PD-L1 and is concordant with clinical assays, but with greater precision. Hierarchical linear modeling can mitigate the effects of intratumoral heterogeneity on immune cell count estimations, allowing for more efficient detection of treatment-related pharmocodynamic effects in the context of clinical trials. Trial registration NCT02950259.

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

2009 ◽  
Vol 117 (2) ◽  
pp. 401-408 ◽  
Author(s):  
G. H. de Bock ◽  
H. Putter ◽  
J. Bonnema ◽  
J. A. van der Hage ◽  
H. Bartelink ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Metastatic Progression ◽  
Multistate Model ◽  
The Impact

Effect of Pregnancy on Overall Survival After the Diagnosis of Early-Stage Breast Cancer

2001 ◽  
Vol 19 (6) ◽  
pp. 1671-1675 ◽  
Author(s):  
Shari Gelber ◽  
Alan S. Coates ◽  
Aron Goldhirsch ◽  
Monica Castiglione-Gertsch ◽  
Gianluigi Marini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Proportional Hazards ◽  
Comparison Group ◽  
Early Stage ◽  
Pregnant Patient ◽  
Subsequent Pregnancy ◽  
Cox Proportional Hazards ◽  
Early Stage Breast Cancer ◽  
Study Group ◽  
The Impact

PURPOSE: To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. PATIENTS AND METHODS: One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. RESULTS: Overall 5- and 10-year survival percentages (± SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% ± 3% and 86% ± 4%, respectively. For the matched comparison group survival was 85% ± 3% at 5 years and 74% ± 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P = .04). CONCLUSION: Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy.

The role of radiotherapy in elderly women with early-stage breast cancer treated with breast conserving surgery

2018 ◽  
Vol 104 (6) ◽  
pp. 429-433 ◽  
Author(s):  
Mariacarla Valli ◽  
Simona Cima ◽  
Paola Fanti ◽  
Barbara Muoio ◽  
Alessandra Vanetti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Elderly Women ◽  
Early Stage ◽  
Conservative Surgery ◽  
Early Stage Breast Cancer ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Significant Difference ◽  
The Impact

Objective: To analyze the impact of adjuvant radiotherapy (RT) on ipsilateral breast recurrence (IBR) and overall survival (OS) in patients older than 69 years with early-stage breast cancer. Methods: From January 2007 to June 2015, we analyzed retrospectively 137 women with estrogen receptor–positive T1–2 invasive breast cancer, with negative axillary lymph nodes, dividing them into 2 subgroups: 70 to 79 years and older than 79 years. Results: After a median follow-up of 43.2 months, the 3-year IBR-free survival in patients treated with surgery plus RT was 98.8% and 92.1% in patients treated with surgery alone, with a significant difference ( p = .01). Radiotherapy did not impact overall survival ( p = .10). A higher percentage of patients aged between 70 and 79 years received RT after conservative surgery if compared with the older subgroup ( p < .01). Conclusions: In elderly women, adjuvant RT reduced the IBR, but did not improve OS.

scholarly journals A review of the impact of exercise on treatment-related fatigue among patients receiving adjuvant radiotherapy for breast cancer

2019 ◽  
Vol 18 (03) ◽  
pp. 295-300 ◽  
Author(s):  
Fiona McNally ◽  
Paul H. Shepherd ◽  
Terri Flood
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Adjuvant Radiotherapy ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Pharmacological Intervention ◽  
Breast Cancer Patients ◽  
Exercise Interventions ◽  
Guidance Needs ◽  
The Impact

AbstractPurposeTo evaluate the use of exercise in managing fatigue in breast cancer patients undergoing adjuvant radiotherapy. To explore the effectiveness of different exercise practices and explore how optimum management of fatigue might be achieved.MethodA CINAHL (Cumulative Index to Nursing and Allied Health Literature) database search of literature was undertaken and publications screened for retrieval with 24 qualifying for inclusion in the review.ResultsThere is evidence to support various forms of exercise including aerobic, resistance, alternative and combination exercise in the management of fatigue in early stage breast cancer patients undergoing adjuvant radiotherapy. The benefits of exercise for patients with later stage and metastatic disease is less clear and there is a lack of published research related to this category of patient.ConclusionExercise is considered a safe, non-pharmacological intervention for early stage breast cancer patients receiving adjuvant radiotherapy. Further investigation is required into optimum exercise interventions and the effectiveness and viability of supervised and unsupervised models. Patient centred tailored advice and guidance needs to be developed and effectively promoted by therapeutic radiographers in order for patients to fully realise the benefit.

scholarly journals Serum Levels of VEGF Pre- and Post-Treatment With Bevacizumab (BEV) for Early Stage Breast Cancer (ESBC): ICORG 08-10

2012 ◽  
Vol 23 ◽  
pp. ix108
Author(s):  
A.M. Canonici ◽  
I. Parker ◽  
T. O'Shea ◽  
B. Moulton ◽  
G. Gullo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Serum Levels ◽  
Post Treatment ◽  
Early Stage Breast Cancer

How radiation oncologist accessibility influences treatment choice and quality in early-stage breast cancer: A SEER database analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6031-6031
Author(s):  
Thomas M. Churilla ◽  
Patrick E. Donnelly ◽  
Christopher A. Peters
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Partial Mastectomy ◽  
Adjuvant Radiation ◽  
Seer Database ◽  
Radiation Oncologist ◽  
Radiation Oncologists ◽  
The Impact

6031 Background: Mastectomy and breast conserving therapy (BCT, partial mastectomy and adjuvant radiotherapy) are equivalent in survival for treatment of early stage breast cancer. This study evaluated the impact of radiation oncologist accessibility on choice of mastectomy versus BCT, and the receipt of radiotherapy after BCT. Methods: In the NCI SEER database, breast cancer cases from 2004-2008 were selected with the following criteria: T2N1M0 or less, lobular or ductal histology, and treatment with simple mastectomy or partial mastectomy (+/-) adjuvant radiation. The HRSA Area Resource File was combined to define average radiation oncologist density (ROD, number of radiation oncologists/100K people) by county over the same time period. Tumor characteristics, demographic information, and ROD were evaluated with respect to mastectomy rates and receipt of radiation therapy after BCT in univariate and multivariate analyses. Results: In the 118,961 cases analyzed, mastectomy was performed 33.3% of the time relative to BCT. After adjustment for demographic and tumor variables, the odds of having mastectomy versus BCT were inversely associated with ROD (OR [95% CI] = 0.94 [0.93-0.96]; p<0.001). Adjuvant radiation therapy was not administered in 23.4% of BCT cases. Likewise, the odds of having BCT without adjuvant radiation were inversely associated with ROD (0.96 [0.95-0.98]; p<0.001, table). Conclusions: There was a significant, inverse and linear relationship between ROD and mastectomy rates independent of demographic and tumor variables. An inverse trend was also observed for the omission of radiotherapy after BCT. Access to radiation oncologists was a factor in surgical choice and receiving appropriate BCT in early stage breast cancer. [Table: see text]

Tumor immune microenvironment (TiME) changes by multiplex IF staining in a pilot study of neoadjuvant talazoparib for early-stage breast cancer patients with a BRCA mutation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 585-585
Author(s):  
Evthokia Hobbs ◽  
Fei Yang ◽  
Tapsi Kumar ◽  
Alejandro Contreras ◽  
Edwin Roger Parra Cuentas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Cancer Patients ◽  
Early Stage ◽  
Post Treatment ◽  
Early Stage Breast Cancer ◽  
Parp Inhibition ◽  
Cytotoxic T Cell ◽  
Breast Cancer Patients

585 Background: We previously reported a median tumor volume loss of 88% (range 30-98%) in 13 patients with early stage BRCA1/2 mutant breast cancer treated on a neoadjuvant trial of the PARP inhibitor talazoparib. The effects of PARP inhibition on immune aspects of the TiME in early-stage breast cancer has not been well described. The goal of this study was to evaluate the TiME in pre and post-treatment core biopsies from enrolled patients. Methods: Eleven paired core biopsies were available for examination. Tumor infiltrating lymphocytes (TILs) were quantified by H&E stained slides by a central pathologist. Specimens were assessed by multiplex immunofluorescence (mIF) using a panel of 6 biomarkers (PD-1, PD-L1, CD3, CD8, CD68 and CK) with the Opal 7-color Kit in LEICA BOND auto stainer, Vectra automated quantitative pathology imaging system and inForm software (PerkinElmer). Results: In the analyzed core biopsies, there was an increase in TILs evaluated by H&E in post-treatment compared to baseline (mean 36 vs 11%). By mIF there was an increase in CD3+ T cell and CD3+CD8+ cytotoxic T cell density in post-treatment samples compared to baseline, summarized in table. PD-L1 expression in tumor cells was rare in the cohort. There was no difference in CD3+PD-1+ or CD3+CD8+ PD-1+ lymphocytes in pre and post-treatment specimens. There was also no differences in macrophages (CD68+). Evaluation of immune phenotype and imaging response will be presented in the final analysis. Conclusions: This is the first study phenotyping the immune response to neoadjuvant talazoparib in BRCA-mutant breast cancer patients. In this small cohort, intratumoral and stromal CD3+ T cells and CD3+CD8+ cytotoxic T cells increased after two months of talazoparib. Clinical trial information: NCT02282345. [Table: see text]

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