Abstract PS18-02: Highly multiplexed tissue-based cyclic immunofluorescence (t-CyCIF) for precision oncology identifies novel patterns of HER2 heterogeneity in breast cancer

2021 ◽  
Author(s):  
Jennifer L Guerriero ◽  
Jia-Ren Lin ◽  
Ricardo G Pastorello ◽  
Ziming Du ◽  
Shaolin Mei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Precision Oncology ◽  
Her2 Heterogeneity

BIOM-32. ENDOPLASMIC RETICULUM PROTEIN SSR3 DETERMINES AND PREDICTS RESPONSE TO PACLITAXEL IN BREAST CANCER AND GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi17-vi18
Author(s):  
Crismita Dmello ◽  
Aarón Sonabend ◽  
Víctor Arrieta ◽  
Daniel Zhang ◽  
Deepak Kanojia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Glioma Cells ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Precision Oncology ◽  
Patient Response ◽  
Knock Out ◽  
Genome Wide ◽  
A Genome

Abstract Paclitaxel (PTX) is one the most potent and commonly used chemotherapies for breast and pancreatic cancer. Given the potency of this drug for glioblastomas (GBM) several ongoing clinical trials are investigating means of enhancing delivery of PTX across the blood-brain barrier for this disease. In spite of the efficacy of PTX, individual tumors exhibit variable susceptibility to this drug, with response rate in the range of 30%-60%. To identify predictive biomarkers for response to PTX, we performed a genome-wide CRISPR knock-out screen using human glioma cells. The most enriched genes in the CRISPR screen underwent further selection based on their correlation with survival in the breast cancer patient cohorts treated with PTX and not in patients treated with other chemotherapies, a finding that was validated on a second independent patient cohort. This led to the discovery of endoplasmic reticulum (ER) protein SSR3 as a putative predictive biomarker for PTX. SSR3 protein levels showed positive correlation with response to PTX in breast cancer cells, glioma cells, in multiple intracranial glioma xenografts and in GBM patient derived explant cultures. Knockout of SSR3 turned the cells resistant to PTX while its overexpression sensitized the cells to PTX. In gliomas, SSR3-mediated susceptibility to PTX relates to modulation of phosphorylation of ER stress sensor IRE1α. Thus, by using genome-wide screen combined with patient response data, we discovered a biomarker that demonstrates causal and correlative relationship with response to PTX in breast cancer and GBM. Prospective validation of this biomarker is warranted for its broad implementation for precision oncology.

scholarly journals CATCH: A Prospective Precision Oncology Trial in Metastatic Breast Cancer

2021 ◽  
pp. 676-686
Author(s):  
Mario Hlevnjak ◽  
Markus Schulze ◽  
Shaymaa Elgaafary ◽  
Carlo Fremd ◽  
Laura Michel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Management ◽  
Metastatic Breast ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Tumor Board ◽  
Precision Oncology ◽  
Whole Genome ◽  
Free Survival

PURPOSE CATCH (Comprehensive Assessment of clinical feaTures and biomarkers to identify patients with advanced or metastatic breast Cancer for marker driven trials in Humans) is a prospective precision oncology program that uses genomics and transcriptomics to guide therapeutic decisions in the clinical management of metastatic breast cancer. Herein, we report our single-center experience and results on the basis of the first 200 enrolled patients of an ongoing trial. METHODS From June 2017 to March 2019, 200 patients who had either primary metastatic or progressive disease, with any number of previous treatment lines and at least one metastatic site accessible to biopsy, were enrolled. DNA and RNA from tumor tissue and corresponding blood-derived nontumor DNA were profiled using whole-genome and transcriptome sequencing. Identified actionable alterations were brought into clinical context in a multidisciplinary molecular tumor board (MTB) with the aim of prioritizing personalized treatment recommendations. RESULTS Among the first 200 enrolled patients, 128 (64%) were discussed in the MTB, of which 64 (50%) were subsequently treated according to MTB recommendation. Of 53 evaluable patients, 21 (40%) achieved either stable disease (n = 13, 25%) or partial response (n = 8, 15%). Furthermore, 16 (30%) of those patients showed improvement in progression-free survival of at least 30% while on MTB-recommended treatment compared with the progression-free survival of the previous treatment line. CONCLUSION The initial phase of this study demonstrates that precision oncology on the basis of whole-genome and RNA sequencing is feasible when applied in the clinical management of patients with metastatic breast cancer and provides clinical benefit to a substantial proportion of patients.

scholarly journals Targeting CD82/KAI1 for Precision Therapeutics in Surmounting Metastatic Potential in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4486
Author(s):  
Maximillian Viera ◽  
George Wai Cheong Yip ◽  
Han-Ming Shen ◽  
Gyeong Hun Baeg ◽  
Boon Huat Bay
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Therapeutic Approach ◽  
Traditional Approach ◽  
Unmet Need ◽  
Great Promise ◽  
Metastasis Suppressor ◽  
Precision Oncology ◽  
Breast Cancer Patients

Metastasis is the main cause of mortality in breast cancer patients. There is an unmet need to develop therapies that can impede metastatic spread. Precision oncology has shown great promise for the treatment of cancers, as the therapeutic approach is tailored to a specific group of patients who are likely to benefit from the treatment, rather than the traditional approach of “one size fits all”. CD82, also known as KAI1, a glycoprotein belonging to the tetraspanin family and an established metastasis suppressor, could potentially be exploited to hinder metastases in breast cancer. This review explores the prospect of targeting CD82 as an innovative therapeutic approach in precision medicine for breast cancer patients, with the goal of preventing cancer progression and metastasis. Such an approach would entail the selection of a subset of breast cancer patients with low levels of CD82, and instituting an appropriate treatment scheme tailored towards restoring the levels of CD82 in this group of patients. Proposed precision treatment regimens include current modalities of treating breast cancer, in combination with either clinically approved drugs that could restore the levels of CD82, CD82 peptide mimics or non-coding RNA-based therapeutics.

scholarly journals Applications of RNA Indexes for Precision Oncology in Breast Cancer

2018 ◽  
Vol 16 (2) ◽  
pp. 108-119 ◽  
Author(s):  
Liming Ma ◽  
Zirui Liang ◽  
Hui Zhou ◽  
Lianghu Qu
Keyword(s):  
Breast Cancer ◽  
Precision Oncology

scholarly journals Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Guan-Tian Lang ◽  
Yi-Zhou Jiang ◽  
Jin-Xiu Shi ◽  
Fan Yang ◽  
Xiao-Guang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Data Exchange ◽  
Large Scale ◽  
Breast Cancer Subtype ◽  
Precision Oncology ◽  
Hippo Signaling ◽  
Breast Cancers ◽  
Loss Of Function ◽  
Clinical Tool ◽  
Clinical Sequencing

Abstract The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.

scholarly journals Circulating tumour DNA in metastatic breast cancer to guide clinical trial enrolment and precision oncology: A cohort study

PLoS Medicine ◽  
2020 ◽  
Vol 17 (10) ◽  
pp. e1003363
Author(s):  
Andjelija Zivanovic Bujak ◽  
Chen-Fang Weng ◽  
Maria João Silva ◽  
Miriam Yeung ◽  
Louisa Lo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Cohort Study ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Precision Oncology ◽  
Circulating Tumour Dna

scholarly journals Liquid Biopsy in Early Breast Cancer: A Preliminary Report

2020 ◽  
pp. 1-8
Author(s):  
Antonio Rulli ◽  
Antognelli Cinzia ◽  
Antonio Rulli ◽  
Covarelli Piero ◽  
Izzo Luciano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Early Stage ◽  
Dynamic Monitoring ◽  
Molecular Profile ◽  
Precision Oncology ◽  
Surgical Biopsy ◽  
Post Surgery ◽  
Genetic Landscape

Background: Liquid biopsy (LB) is a technique that utilizes circulating biomarkers from cancer patients to provide information regarding the genetic landscape of the cancer. LB is emerging as an alternative and complementary diagnostic and prognostic tool to surgical biopsy and is expected to provide the tool for the implementation of precision oncology in clinical settings. In fact, it may contribute to enhance understanding of tumor heterogeneity and permitting the dynamic monitoring of treatment responses and genomic variations. Thus, LB is a promising method for the management of cancer, including breast cancer (BC), whose incidence in Italy is progressively increasing. Previous studies focused mainly on patients with advanced-stage BC. In the present study we evaluated the number of circulating tumor cells (CTCs), the quantity of cell free tumor DNA (cftDNA) and the analysis of the mutational profile of DNA from CTCs (ctcDNA) and cftDNA in early stage BC patients. Methods: Matched pre- and post-surgery blood samples were collected from 47 early stage BC patients. CTCs enumeration was done using Isoflux system, molecular profile of ctcDNA and cftDNA was performed with the Spotlight 59 Panels kit on a MiSeq Illumina instrument. Results: Eighty percent of samples was CTCs-positive, while healthy controls were all CTCs-negative. Forty-four patients provided a pre-surgery and 21 post-surgery sample. By comparing the number of CTCs post-surgery with that of pre-surgery, we found that 66% of patients showed a decreased number of CTCs, 14% of patients continued to have the same number of CTCs, while, interestingly, 19% of patients showed an increased number of CTCs. Next Generation Sequencing (NGS) of ctcDNA and cftDNA showed that 52% of samples had mutations in 9 genes (TP53, CDKN2A, FBXW7, PTPN11, KRAS, NRAS, BRAF, IDH1, ALK) and in 5 genes (PIK3CA, APC ALK, KRAS, TSC1), respectively, with KRAS and ALK overlapping and TP53 being the most frequently mutated gene in ctcDNA analysis. Conclusions: LB could facilitate early detection of minimal residual disease, aiding in the initiation of adjuvant therapy to prevent recurrence and progression towards metastasis, enhance individualized treatment and longitudinal screening, thus improving the clinical management and outcome of patients with early BC.

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