PO-1085 Longitudinal assessment of immune infiltrate in breast cancer treated with neoadjuvant radiotherapy

2021 ◽  
Vol 161 ◽  
pp. S902-S904
Author(s):  
R. Robinson ◽  
I. Roxanis ◽  
F. Sobhani ◽  
K. Zormpas-Petridis ◽  
H. Steel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Longitudinal Assessment ◽  
Neoadjuvant Radiotherapy ◽  
Immune Infiltrate

scholarly journals Immune microenvironment and intrinsic subtyping in hormone receptor-positive/HER2-negative breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Gaia Griguolo ◽  
Maria Vittoria Dieci ◽  
Laia Paré ◽  
Federica Miglietta ◽  
Daniele Giulio Generali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Gene Expression Data ◽  
Hormone Receptor ◽  
Tumor Biology ◽  
Expression Data ◽  
Immune Microenvironment ◽  
Immune Infiltrate ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer

AbstractLittle is known regarding the interaction between immune microenvironment and tumor biology in hormone receptor (HR)+/HER2− breast cancer (BC). We here assess pretreatment gene-expression data from 66 HR+/HER2− early BCs from the LETLOB trial and show that non-luminal tumors (HER2-enriched, Basal-like) present higher tumor-infiltrating lymphocyte levels than luminal tumors. Moreover, significant differences in immune infiltrate composition, assessed by CIBERSORT, were observed: non-luminal tumors showed a more proinflammatory antitumor immune infiltrate composition than luminal ones.

scholarly journals Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival

2017 ◽  
Vol 19 (1) ◽  
Author(s):  
Jan Poleszczuk ◽  
Kimberly Luddy ◽  
Lu Chen ◽  
Jae K. Lee ◽  
Louis B. Harrison ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Neoadjuvant Radiotherapy ◽  
Free Survival ◽  
Disease Free

Abstract P5-04-10: Characterization of the immune infiltrate in HER2+ breast cancer

2015 ◽  
Author(s):  
Shridar Ganesan ◽  
Gabriela Alexe ◽  
Kim M Hirshfield ◽  
Ming Yao ◽  
Gyan Bhanot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Infiltrate ◽  
Her2 Breast Cancer

scholarly journals Neoadjuvant radiotherapy in the approach of locally advanced breast cancer

ESMO Open ◽  
2020 ◽  
Vol 5 (2) ◽  
pp. e000640 ◽  
Author(s):  
Cláudia Sousa ◽  
Mafalda Cruz ◽  
Ana Neto ◽  
Kayla Pereira ◽  
Marta Peixoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Intrinsic Subtype ◽  
Advanced Breast ◽  
Neoadjuvant Radiotherapy ◽  
The Impact

BackgroundApproximately 4% of European patients are diagnosed with locally advanced breast cancer (LABC), a clinical condition commonly associated with poorer prognosis. Systemic therapy is the recommended initial treatment and when inoperability criteria prevails, radiotherapy (RT) should be used for tumour downstaging. This study intends to evaluate the impact of neoadjuvant radiotherapy (NART) in the treatment of inoperable LABC.MethodsA retrospective study of female patients, submitted to the NART between January 2014 and December 2018 at our institution. The evaluation of pathological response (pR) was made based on Pinder criteria. Primary endpoint: pR. Secondary endpoints: overall survival (OS) and progression-free survival (PFS). OS and PFS were calculated using the Kaplan-Meier method. Differences between groups were compared using Student’s t-test, ANOVA (Analysis of variance) and χ2 test. The statistical analyses were performed using Stata (V.13).ResultsA total of 76 patients were included, 18% with breast complete response. The 5 years OS was 54% and PFS was 61%. Subgroup analysis showed that pR >90% is correlated with a better OS (p=0.004). Basal-like intrinsic subtype is correlated with worse OS and PFS (p<0.05). No relation was found between response and age, intrinsic subtype, treatment performed and clinical T stage.ConclusionOur study confirms that NART is an effective downsizing treatment in inoperable LABC, allowing for a surgical resection regardless of the systemic treatment performed. Response to NART is independent of the intrinsic subtype and pR >90% is correlated with a better OS. Prospective studies to explore predictive response biomarkers are necessary in order to improve patient selection and optimisation of the treatment.

scholarly journals Decoding Immune Heterogeneity of Triple Negative Breast Cancer and Its Association with Systemic Inflammation

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 911 ◽  
Author(s):  
Romero-Cordoba ◽  
Meneghini ◽  
Sant ◽  
Iorio ◽  
Sfondrini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Inflammation ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cytolytic Activity ◽  
Local Composition ◽  
Immune Infiltrate

Triple negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options. New opportunities are emerging from current comprehensive characterization of tumor immune infiltration and fitness. Therefore, effectiveness of current chemotherapies and novel immunotherapies are partially dictated by host inflammatory and immune profiles. However, further progress in breast cancer immuno-oncology is required to reach a detailed awareness of the immune infiltrate landscape and to determine additional reliable and easily detectable biomarkers. In this study, by analyzing gene expression profiles of 54 TNBC cases we identified three TNBC clusters displaying unique immune features. Deep molecular characterization of immune cells cytolytic-activity and tumor-inflammation status reveled variability in the local composition of the immune infiltrate in the TNBC clusters, reconciled by tumor-infiltrating lymphocytes counts. Platelet-to-lymphocyte ratio (PLR), a blood systemic parameter of inflammation evaluated using pre-surgical blood test data, resulted negatively correlated with local tumoral cytolytic activity and T cell–inflamed microenvironment, whereas tumor aggressiveness score signature positively correlated with PLR values. These data highlighted that systemic inflammation parameters may represent reliable and informative markers of the local immune tumor microenvironment in TNBC patients and could be exploited to decipher tumor infiltrate properties and consequently to select the most appropriate therapies.

scholarly journals Characterization of the relationship between FLI1 and immune infiltrate level in tumour immune microenvironment for breast cancer

2020 ◽  
Vol 24 (10) ◽  
pp. 5501-5514
Author(s):  
Shiyuan Wang ◽  
Yakun Wang ◽  
Chunlu Yu ◽  
Yiyin Cao ◽  
Yao Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Microenvironment ◽  
Immune Infiltrate ◽  
The Relationship

The landscape of genomic alterations detected in serial circulating tumor DNA (ctDNA) in clinical progressive metastatic breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1084-1084
Author(s):  
Saya Jacob ◽  
Andrew A. Davis ◽  
Lorenzo Gerratana ◽  
Ami N. Shah ◽  
Neelima Katam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Wilcoxon Test ◽  
Bone Lesions ◽  
Tumor Evolution ◽  
Longitudinal Assessment ◽  
Clinical Progression ◽  
The Impact

1084 Background: Metastatic breast cancer (MBC) is associated with genomic evolution, representing a challenge at clinical progression. While tissue and blood next-generation sequencing (NGS) allows for the baseline detection of alterations, non-invasive longitudinal assessment of ctDNA can provide a tool for monitoring tumor evolution. We characterized genomic changes using serial ctDNA testing in patients with clinical progression. Methods: Patient data was obtained under an IRB-approved protocol and ctDNA was collected at Northwestern University between 2015-2019. All ctDNA samples were analyzed using the Guardant360 NGS assay. Of 255 patients with MBC, 86 had at least two serial ctDNA collections with the second collection drawn at first progression (P1) by imaging and clinical assessment. Participants were followed until second clinical progression (P2). We analyzed type of alterations, mutant allele frequency (MAF), number of alterations (NOA), and sites of disease on imaging in close proximity to ctDNA evaluation. Matched pairs variations in MAF and NOA at P1 and P2 were tested through Wilcoxon test. Results: We identified 44 HR+, 20 HER2+ and 22 TNBC cases. Median lines of therapy were 3 (interquartile range (IQR): 1-6) for HR+, 3 (IQR: 1-5) for HER2+, and 2 (IQR: 1-4) for TNBC. The most likely alterations between baseline to P1 were TP53 (p < 0.0075), PIK3CA (p < 0.0126), AR (p < 0.0126), FGFR1 (p < 0.0455) and ESR1 (p < 0.0143). In the HR+ subset , ESR1 was statistically more likely at P1. ESR1 at P1 was also associated with development of new liver lesions (p < 0.0320). ERBB2 mutation at P1 was associated with new lung (p < 0.0050) or bone lesions (p < 0.0030). Increase in NOA was observed between baseline and P1 (p < 0.0001), P1 and P2 (p < 0.0001), and baseline to P2 (p < 0.0004). MAF was increased between baseline and P2 (p < 0.0480). Conclusions: Serial ctDNA testing identified resistance alterations ( TP53, PIK3CA, AR, ESR1, FGFR1), with some mutations indicating new sites of disease ( ESR1, ERBB2). Heterogeneity of ctDNA was significantly associated with progressive disease. Prospective evaluation of the impact of serial ctDNA testing on treatment decisions is needed to expand the role of precision medicine in MBC. [Table: see text]

scholarly journals Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07)

2020 ◽  
Author(s):  
Sara A Hurvitz ◽  
Jennifer L Caswell-Jin ◽  
Katherine L McNamara ◽  
Jason Zoeller ◽  
Gregory R Bean ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Early Stage ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Early Assessment ◽  
Her2 Positive ◽  
Immune Infiltrate ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

In this neoadjuvant trial (TRIO-US B07), participants with early-stage HER2-positive breast cancer (N=128) were randomized to receive trastuzumab (T), lapatinib (L), or both (TL) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. We observed similar pathologic complete response (pCR) rates between T and TL, and a lower pCR rate with L. Higher-level amplification of HER2 and hormone receptor-negative status were associated with a higher pCR rate. Higher pre-treatment immune infiltrate trended toward higher pCR rate in T-treated groups, and greater HR expression correlated with lower immune infiltrate. Large shifts in tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents.

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