Prediction of Resistance and Sensitivity to HER2 Targeted Therapy in the Neoadjuvant Setting
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PROVIDER: PRJNA957549 | ENA |
REPOSITORIES: ENA
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Project description:Prediction of Resistance and Sensitivity to HER2 Targeted Therapy in the Neoadjuvant Setting
| PRJNA957548 | ENA
Project description:We identified a 17-gene Her2-enriched tumor initiating cell (HTIC) signature in MMTV-Her2/Neu mouse mammary TICs. Here, we show that patients with HTICS+ HER2+:ERα− tumors are more likely to achieve a pathologic complete response to trastuzumab-based neoadjuvant chemotherapy compared with HER2+:ER+ tumors. Neoadjuvant study of 50 HER2-positive breast cancer cases treated with trastuzumab-based chemotherapy pre-operatively. Pre-treatment FNA from primary tumors were obtained and RNA extracted and hybridized to Affymetrix microarrays according to manufacturer protocol. Pathologic response was assessed at the end of neoadjuvant treatment.
2012-05-11 | E-GEOD-37946 | biostudies-arrayexpress
Project description:Trastuzumab, a humanized monoclonal antibody directed to the HER2 protein, is the standard-of-care treatment for patients with HER2 positive breast cancer, reducing the risk of relapse and death in patients. Nonetheless, some patients do not benefit from this treatment, underscoring the need to identify patients for whom chemotherapy + trastuzumab is adequate versus patients requiring additional drugs. The series comprised 24 incisional biopsies of breast carcinomas derived from patients that received neoadjuvant trastuzumab based therapy. Gene expression profiling was performed using RNA from frozen core biopsies from 24 patients with primary HER2-positive (HER2+) tumors treated with neoadjuvant chemotherapy and trastuzumab.
2016-03-31 | E-GEOD-62327 | biostudies-arrayexpress
Project description:We identified a 17-gene Her2-enriched tumor initiating cell (HTIC) signature in MMTV-Her2/Neu mouse mammary TICs. Here, we show that patients with HTICS+ HER2+:ERα− tumors are more likely to achieve a pathologic complete response to trastuzumab-based neoadjuvant chemotherapy compared with HER2+:ER+ tumors.
2012-05-12 | GSE37946 | GEO
Project description:Background: Neoadjuvant chemotherapy is increasingly being used to preoperatively shrink breast tumours prior to surgery. This approach also provides the opportunity to study the molecular changes associated with treatment and evaluate whether on-treatment sequential samples can improve response and outcome predictions over diagnostic or excision samples alone. Methods: A total of 95 samples from a cohort of 50 neoadjuvant chemotherapy-treated primary breast cancer patients (aged 29-76, 48% ER+, 20% HER2+) enrolled in the NEO trial taken before, at 2 weeks on-treatment, mid-therapy and at resection were sequenced with Ion Ampliseq transcriptome yielding expression values for 12,635 genes. Differential expression analysis was performed across 16 responders and 34 non-responders defined by pathological complete response and over treatment time to identify significantly differentially expressed genes, pathways and markers indicative of response status. Prediction accuracy was compared with estimations of established gene signatures, for this dataset and validated using data from the I-SPY1 trial. Results: AAGAB was identified as a novel on-treatment biomarker for pathological complete response, with an accuracy of 100% in the NEO training dataset and 78% accuracy in the I-SPY1 Trial. AAGAB levels on treatment were also significantly predictive of term survival (p = 0.048, p = 0.031) in the two cohorts. This single gene on-treatment biomarker, had greater predictive accuracy than established prognostic tests, Mammaprint and Pam50 risk of recurrence score, although interesting both of these tests performed better in the on-treatment rather than the accepted pre-treatment setting (accuracy improving consistently by 2-8%). Conclusion: Changes in gene expression measured in sequential samples from breast cancer patients receiving neoadjuvant chemotherapy resulted in the identification of a novel on-treatment biomarker and suggest that established prognostic tests may have greater prediction accuracy on- than before treatment. These results support the potential use and further evaluation of on- treatment testing in breast cancer to improve the accuracy of tumour response prediction.
2019-07-02 | GSE122630 | GEO
Project description:Pathological complete response (pCR) after neoadjuvant therapy is a robust surrogate marker for long-term outcomes in breast cancer. However, reliable biomarkers predicting pCR in HER2-positive breast cancer remain elusive Transcriptomic profiling to identify candidate genes associated with pCR were performed in patients with HER2-positive, hormone receptor–negative breast cancer treated with neoadjuvant chemotherapy plus anti-HER2 agents
2026-03-23 | GSE310900 | GEO
Project description:Co-expression of the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) contributes to breast cancer heterogeneity and therapeutic resistance. Tumors expressing both ER and HER2 comprise up to 10% of diagnosed breast cancer cases, yet advances in the field have been hindered by the lack of suitable genetically engineered mouse models (GEMMs) to study the interactions between HER2 and ER in an immune-competent setting. Here, we demonstrate that expression of the oncogenic HER2 splice variant lacking exon 16 (HER2∆16) within the mammary epithelium promotes the development of aggressive luminal tumors, resembling HER2+/ER+ human breast cancer. Expression of HER2∆16 facilitates luminal cell differentiation and drives an ER-mediated transcriptional program that is sensitive to endocrine-based therapies in both murine and human models. Using a knock-in GEMM where HER2∆16 is under the transcriptional control of the endogenous murine ErbB2 promoter we show that this model recapitulates many features of HER2+/ER+ human breast cancer including genomic amplification of the endogenous ErbB2 allele, ER-expression and sensitivity to anti-estrogens, providing a vital preclinical platform to model ER+/HER2+ disease. HER2∆16 is expressed across HER2+ human breast cancer cell lines with higher levels correlating with increased expression of both ER and downstream transcriptional targets. Interestingly, expression of HER2∆16 is increased upon resistance to HER2-targeted therapy, leading to an ER-driven transcriptional program which can be effectively targeted using ER-antagonists. Overall, these findings offer valuable mechanistic insights into the therapeutic efficacy of combining anti-HER2 and endocrine therapy in tumors expressing high levels of the HER2∆16 isoform either in neoadjuvant or adjuvant settings to better treat HER2+ disease.
2026-05-16 | GSE301629 | GEO
Project description:Trastuzumab, a humanized monoclonal antibody directed to the HER2 protein, is the standard-of-care treatment for patients with HER2 positive breast cancer, reducing the risk of relapse and death in patients. Nonetheless, some patients do not benefit from this treatment, underscoring the need to identify patients for whom chemotherapy + trastuzumab is adequate versus patients requiring additional drugs. The series comprised 18 incisional biopsies of breast carcinomas derived from patients that received neoadjuvant trastuzumab based therapy.
2021-12-31 | GSE149283 | GEO
Project description:Trastuzumab, a humanized monoclonal antibody directed to the HER2 protein, is the standard-of-care treatment for patients with HER2 positive breast cancer, reducing the risk of relapse and death in patients. Nonetheless, some patients do not benefit from this treatment, underscoring the need to identify patients for whom chemotherapy + trastuzumab is adequate versus patients requiring additional drugs. The series comprised 24 incisional biopsies of breast carcinomas derived from patients that received neoadjuvant trastuzumab based therapy.
2016-03-31 | GSE62327 | GEO
Project description:Abstract Motivation Breast cancer is a heterogeneous disease with distinct subtypes. Even within these subtypes differences at the molecular level are present which are reflected in variable responses to chemotherapy. We set out to identify genes associated with chemotherapy resistance by analyzing a set of HER2-positive breast cancers. Methods We collected, gene expression profiled and analyzed 60 HER2-positive breast tumor biopsies, obtained from patients scheduled to undergo neoadjuvant therapy. In addition to conventional supervised approaches for the detection of reporters of resistance, we report on a novel approach specifically tailored to the detection of small groups of resistant samples that show aberrant gene expression patterns. Results We propose a novel analytical approach that takes heterogeneity in response into account. We show that this approach is more powerful than classical approaches for detecting small subgroups of samples showing aberrant expression in a controlled setting. We applied this approach to our 60 breast cancer samples prior to neoadjuvant chemotherapy, and generated candidate response reporter lists for each subtype. Discussion Using a novel analytical approach we report on the mRNA gene expression analysis of a cohort of breast cancers prior to neoadjuvant chemotherapy. An important characteristic of this approach is that it takes heterogeneity in neoadjuvant treatment response into account. Such approaches are needed to identify biomarkers for predicting treatment response. We collected, gene expression profiled and analyzed 60 breast tumor biopsies, obtained from patients scheduled to undergo neoadjuvant therapy.
2013-10-22 | E-GEOD-41656 | biostudies-arrayexpress