A gene expression signature of Retinoblastoma loss-of-function predicts resistance to neoadjuvant chemotherapy in ER-positive/HER2-positive breast cancer patients

The lipid tumour demand may shape the host metabolism adapting the circulating lipids composition to its growth and progression needs. This study aims to exploit the straightforward 1H-NMR lipoproteins analysis to investigate the alterations of the circulating lipoproteins’ fractions in HER2-positive breast cancer and their modulations induced by treatments. The baseline 1H-NMR plasma lipoproteins profiles were measured in 43 HER2-positive breast cancer patients and compared with those of 28 healthy women. In a subset of 32 patients, longitudinal measurements were also performed along neoadjuvant chemotherapy, after surgery, adjuvant treatment, and during the two-year follow-up. Differences between groups were assessed by multivariate PLS-DA and by univariate analyses. The diagnostic power of lipoproteins subfractions was assessed by ROC curve, while lipoproteins time changes along interventions were investigated by ANOVA analysis. The PLS-DA model distinguished HER2-positive breast cancer patients from the control group with a sensitivity of 96.4% and specificity of 90.7%, mainly due to the differential levels of VLDLs subfractions that were significantly higher in the patients' group. Neoadjuvant chemotherapy-induced a significant drop in the HDLs after the first three months of treatment and a specific decrease in the HDL-3 and HDL-4 subfractions were found significantly associated with the pathological complete response achievement. These results indicate that HER2-positive breast cancer is characterized by a significant host lipid mobilization that could be useful for diagnostic purposes. Moreover, the lipoproteins profiles alterations induced by the therapeutic interventions could predict the clinical outcome supporting the application of 1H-NMR lipoproteins profiles analysis for longitudinal monitoring of HER2-positive breast cancer in large clinical studies.

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Combination of Nab-Paclitaxel with Trastuzumab as Neoadjuvant Chemotherapy for HER2-positive Breast Cancer Patients: Experience from a Single Center

Clinical and Experimental Pharmacology ◽

10.4172/2161-1459.1000209 ◽

2016 ◽

Vol 06 (03) ◽

Author(s):

Li T ◽

Yang M

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Single Center ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Patients Experience ◽

Positive Breast Cancer

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PD-1-Associated Gene Expression Signature of Neoadjuvant Trastuzumab-Treated Tumors Correlates with Patient Survival in HER2-Positive Breast Cancer

Cancers ◽

10.3390/cancers11101566 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1566 ◽

Cited By ~ 3

Author(s):

William P. D. Hendricks ◽

Natalia Briones ◽

Rebecca F. Halperin ◽

Salvatore Facista ◽

Paul R. Heaton ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Gene Expression Signature ◽

Predictive Biomarkers ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Expression Signature ◽

Her2 Breast Cancer ◽

Group 2

The therapeutic HER2-targeting antibody trastuzumab has been shown to elicit tumor immune response in a subset of HER2-positive (HER2+) breast cancer. We performed genomic and immunohistochemical profiling of tumors from eight patients who have completed multiple rounds of neoadjuvant trastuzumabb to identify predictive biomarkers for trastuzumab-elicited tumor immune responses. Immunohistochemistry showed that all tumors had an activated tumor immune microenvironment positive for nuclear NF-κB/p65RelA, CD4, and CD8 T cell markers, but only four out of eight tumors were positive for the PD-1 immune checkpoint molecule, which is indicative of an exhausted immune environment. Exome sequencing showed no specific driver mutations correlating with PD-1 positivity. Hierarchical clustering of the RNA sequencing data revealed two distinct groups, of which Group 2 represented the PD-1 positive tumors. A gene expression signature that was derived from this clustering composed of 89 genes stratified HER2+ breast cancer patients in the TCGA dataset and it was named PD-1-Associated Gene Expression Signature in HER2+ Breast Cancer (PAGES-HBC). Patients with the Group 2 PAGES-HBC composition had significantly more favorable survival outcomes with mortality reduced by 83% (hazard ratio 0.17; 95% CI, 0.05 to 0.60; p = 0.011). Analysis of three longitudinal samples from a single patient showed that PAGES-HBC might be transiently induced by trastuzumab, independent of clonal tumor expansion over time. We conclude that PAGES-HBC could be further developed as a prognostic predictor of trastuzumab response in HER2+ breast cancer patients and be potentially used as an alternative biomarker for anti-PD-1 therapy trials.

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