Abstract 437: Comprehensive genomic profiling (CGP) in breast cancer (BC): Patterns and results from a clinico-genomic database

2021 ◽  
Author(s):  
Achim Rody ◽  
Nayan Chaudhary ◽  
Christopher Craggs ◽  
Marcio Debiasi ◽  
Gilles Erb ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genomic Profiling ◽  
Genomic Database ◽  
Comprehensive Genomic Profiling

scholarly journals A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient

2016 ◽  
Vol 9 (1) ◽  
pp. 112-118 ◽  
Author(s):  
Siraj M. Ali ◽  
Jessica Watson ◽  
Kai Wang ◽  
Jon H. Chung ◽  
Caitlin McMahon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Hospice Care ◽  
Treatment Initiation ◽  
Clinical Care ◽  
Metastatic Breast ◽  
Genomic Profiling ◽  
Treatment Resistant ◽  
Bcl2 Family ◽  
Comprehensive Genomic Profiling

After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%). A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients.

scholarly journals Biomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD‐L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer

2020 ◽  
Vol 25 (11) ◽  
pp. 943-953 ◽  
Author(s):  
Richard S.P. Huang ◽  
Xinyan Li ◽  
James Haberberger ◽  
Ethan Sokol ◽  
Eric Severson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Integrated Analysis ◽  
Genomic Profiling ◽  
Comprehensive Genomic Profiling

Identification of kinase domain duplications across diverse cancer types in Chinese population by comprehensive genomic profiling (CGP).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13522-e13522
Author(s):  
Baohua Wang ◽  
Ruoying Yu ◽  
Qiuxiang Ou ◽  
Hua Bao ◽  
Xue Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Lung Cancer ◽  
Total Population ◽  
Target Therapy ◽  
Kinase Domain ◽  
Genomic Profiling ◽  
Multiple Cancer ◽  
Comprehensive Genomic Profiling ◽  
Cancer Types

e13522 Background: Kinase domain duplication (KDD) has recently been recognized as oncogenic and targetable mutations in some cancers. EGFR KDD was identified as an oncogenic driver in lung cancer showing partial response to EGFR TKI. BRAF KDD was reported in diverse tumor types with clinical response to RAF-targeted therapy. We retrospectively investigated the prevalence of KDDs in multiple cancer types of a large Chinese population. Methods: 50742 unique cancer cases were analyzed by comprehensive genomic profiling (CGP). DNA was extracted from formalin-fixed paraffin-embedded specimens (FFPEs), fresh tissue, blood or plasma samples and sequenced with gene panels targeting 400+ cancer-relevant genes. Among them, 53 cases were detected with KDD of various kinases. Results: In this Chinese cohort, KDD was identified in 0.1% of the total population across multiple cancer types including lung cancer (39), breast cancer (5), gastric cancer (3), colorectal cancer (2), mucoepidermoid carcinoma (1), unknown (3). The median age at diagnosis was 54 which was younger than the 60 yrs median age of total population. The distribution of KDDs was in EGFR(34) MET(5), JAK1(2), BRAF(2), FGFR2(2), FGFR1(1), JAK2(1), LYN(1), MAP3K1(1), RAF1(1), RET(1), AKT3(1), and CDK8(1). Thirty-one lung cancer cases were detected with EGFR-KDD, including kinase duplications of exon18-25 (22), exon17-25 (6), exon18-26 (2), exon14-26(1). Three patients with EGFR-KDD exon18-25 showed partial anti-tumor response to target therapy. MET-KDD was exclusively found in lung cancer involving the duplication of MET exon15-21 (2), exon14-17 (1), exon15-16 (1) and exon12-21 (1) while FGFR1/2-KDD was observed only in gastric cancer. Two female patients with breast cancer were detected with JAK1-KDD at age of 45 and 37, respectively. The canonical BRAF-KDD of exon 10-18 was identified in one female patient diagnosed of lung adenocarcinoma at age of 49. Frequently altered genes in patients with KDD were TP53(72%), EGFR (23%), FAT1(13%), BRCA1(10%). MCL1 amplification, a known oncogenic alteration, was identified in fifteen patients (11 EGFR-KDD,2 MET-KDD, 1 BRAF-KDD, 1 JAK2-KDD), representing the most common copy number variation observed. Conclusions: Kinase KDDs were rare but potentially oncogenic mutations in diverse cancer types with clinical outcome of EGFR-KDD to target therapy in lung cancer. Cancer-type specific KDDs were identified including MET-KDD in lung cancer, FGFR1/2-KDD in gastric cancer and JAK1-KDD in breast cancer.

Clinical implications of genomic-directed therapies by comprehensive genomic profiling in breast cancer patients at a large academic cancer center.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12037-e12037
Author(s):  
Ricardo Daniel Parrondo ◽  
Veronica Mariotti ◽  
Miguel Gonzalez Velez ◽  
Lori Ann Leslie
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Pik3ca Mutation ◽  
Clinical Impact ◽  
Cancer Center ◽  
Genomic Profiling ◽  
Breast Cancer Patients ◽  
Comprehensive Genomic Profiling ◽  
Genomic Characterization

e12037 Background: Increased use of comprehensive genomic profiling (CGP) has recently led to improved genomic characterization of tumors, increased access to individualized therapies and increased availability of clinical trials in breast cancer patients. The aim of this study was to evaluate the clinical impact of genomic profiling in breast cancer patients with the use of a CGP assay at a large cancer center. Methods: We retrospectively analyzed 101 consecutive breast cancer patients who received CGP at the John Theurer Cancer Center between 12/2011 and 08/2016. Genomic alterations (GAs) were identified using the FoundationOne assay (Foundation Medicine, Cambridge, MA). GAs, number of available genomic-directed therapies and number of available clinical trials were reviewed. The CGP interrogated up to 315 genes and introns of 28 genes. Results: Median age at diagnosis was 58 years (range: 35-83 years). With a median follow-up of 189 months (range 1-189), median survival was 163 months (range 142-184). A total of 560 GAs were found in our population, with a median of 5.0 GAs/sample (range 0-16), a median of 2.0 therapies/patient (range 0-11), and a median of 11.0 clinical trials/patient (range 0-36). The most frequent GAs found were TP53 (47.5%, n = 48), PIK3CA (34.7%, n = 35), MYC (22.8%, n = 23), CCND1 (19.8%, n = 20), FGF3 (16.8%, n = 17), FGF4 (15.8%, n = 16), and ZNF703 (14.9%, n = 15). A significant positive correlation was found between number of GAs and the number of available targeted therapies and clinical trials (r = 0.5 and r = 0.7, p = 0.00, respectively). Increasing age is a predictor of having a PIK3CA mutation (OR = 1.05; CI:1.01-1.09, p = 0.00) while decreasing age is a predictor of having a MYC mutation by logistic regression (OR = 0.95; CI:0.91-0.95, p = 0.03). Conclusions: The systematic use of CGP led to the identification of a high number of GAs, which correlated with a median of 2.0 individualized therapies and a median of 11.0 clinical trials available for breast cancer patients. The clinical impact of genomic-directed individualized therapies needs to be further investigated in prospective, randomized studies.

Immunotherapy predictive biomarkers in metastatic breast cancer (MBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1023-1023
Author(s):  
Jeffrey S. Ross ◽  
Ethan Sokol ◽  
Lee A. Albacker ◽  
Garrett M. Frampton ◽  
Dean Pavlick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Predictive Biomarkers ◽  
Genomic Profiling ◽  
Hybrid Capture ◽  
Capture Assay ◽  
Mutational Burden ◽  
Comprehensive Genomic Profiling ◽  
Tumor Mutational Burden ◽  
Mdm2 Amplification

1023 Background: We queried whether comprehensive genomic profiling (CGP) of mBC subtypes could identify biomarkers that have been linked to responsiveness to immunotherapy (IO) treatments. Methods: DNA was extracted from 3,871mBC: 1,388 ER+/HER2-, 1,969 HER2 amplified (amp) and 643 TNBC. CGP was performed using a hybrid-capture assay. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci in 564 cases. PD-L1 was determined by IHC (Dako 22C3). Results: Patient ages were similar. Genomic alterations (GA)/tumor were similar ranging from 5.9 to 7.3. MTOR pathway targets were common; lowest in TNBC. CDH1 and ESR1 GA most frequent in ER+/HER2- cases. ERBB2 short variant (SV) mut were most frequent in ER+/HER2- and HER2 amp and not seen in TNBC. Other kinase targets were uncommon except for FGFR1 GA in ER+/HER2-. BRCA1/ 2 GA least frequent in HER2 amp. AR was amplified in 1% of all mBC. Markers of potential IO benefit: CD274 ( PD-L1) amp (1-3%), BRAF GA (1-4%), TMB of ≥10 mut/Mb (8-12%), TMB of ≥20 mut/Mb (2-3%), MSI-High (0.1-0.4%), PBRM1 GA (1%) and low (1-10%) or high (0-3%) PD-L1 staining. Potential markers of resistance: inactivating GA in STK11 (1-2%) and MDM2 amplification (3-6%). Examples of mBC patients responding to IO therapies will be presented. Conclusions: In addition to guiding targeted therapy selection, CGP shows potential to identify GA linked to response and resistance to IO in mBC. The demonstrations of clinical benefit of immunotherapy in mBC supports the need for the development of biomarkers used to guide the use of ICPI drugs for these patients. [Table: see text]

Next generation sequencing reveals CCNE1 amplification as an independent prognostic factor for triple negative breast cancer (TNBC) patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 558-558
Author(s):  
Xin Huang ◽  
Huanwen M. Wu ◽  
Changbin Zhu ◽  
Di Shao ◽  
Dan Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Copy Number ◽  
Triple Negative ◽  
Genetic Data ◽  
Genetic Alterations ◽  
Clinicopathological Parameters ◽  
Genomic Profiling ◽  
Cyclin E1 ◽  
Comprehensive Genomic Profiling

558 Background: Triple negative breast cancer (TNBC) has the worst prognosis among breast cancer due to the heterogeneity as well as lack of better therapeutic approach. It remains controversial whether BRCA status is the predictor of survival in TNBC. Besides, both germline and somatic mutation may contribute to the prognosis. This study is to explore the potential predictors and therapeutic targets based on genetic data and clinicopathological parameters. Methods: Seventy-five TNBC patients were enrolled with approximately 2:1 based on BRCA status. Genetic data was analysed by comprehensive genomic profiling 508 key cancer related genes. DAVID was applied to perform pathway enrichment analysis of significant enriched genetic alterations. Cox regression model was applied to evaluate disease-free survival (DFS) and overall survival (OS). Immuno-chemistry (IHC) was used to validate clinically meaningful genetic alteration. Results: In this study, 27 germline mutations were detected, including 26 homologous recombination repair (HRR) pathway gene mutations and 1 mismatch repair gene mutation among them 16 BRCA1 mutations and 5 BRCA2 mutations were found. Germline HRR including BRCA1/2 mutation marginally affected DFS ( p = 0.0624 and 0.15, respectively). We found 480 somatic genetic alterations including 110 copy number variations (CNV). The median value of TMB was determined to be 4.1 Muts/Mb which divided 74 TNBC patients into TMB-low (TMB-l) and TMB-high (TMB-h) group. TMB-l group had inferior DFS to TMB-h ( p = 0.0457). CCNE1 (with 5% frequency) copy number gain was specifically enriched in TMB-l group but mutually exclusive with BRCA1/2 mutation. TNBC with CCNE1 gain displayed worse DFS ( p< 0.0001). Cox multivariate regression analysis indicated CCNE1 gain was an independent risk factors for DFS [HR = 13.48 (95% CI 2.62-69.23), p= 0.002)]. Pathway analysis indicated CCNE1 harmed prognosis through regulation of transcription in G1/S phase. Expression of cyclin E1 was validated by IHC, which would be presented later. Conclusions: Comprehensive genomic profiling disclosed various potential prognostic markers for TNBC by integrating clinical characters. Especially, amplified CCNE1 may be a potential prognostic marker and therapeutic target. [Table: see text]

Clinical relevance of comprehensive genomic profiling for advanced cancers in India.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18718-e18718
Author(s):  
Serena Elizabeth Joseph ◽  
Aju Mathew ◽  
Senthill J. Rajappa ◽  
Nitesh Rohatgi ◽  
Bhawna Sirohi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Targeted Therapy ◽  
Genetic Alteration ◽  
Insertion Mutation ◽  
Study Cohort ◽  
Genomic Profiling ◽  
Her2 Amplification ◽  
Low Middle Income Countries ◽  
Comprehensive Genomic Profiling

e18718 Background: Comprehensive genomic profiling (CGP) assay, a next-generation sequencing (NGS) based technique generates a large amount of genomic information about a cancer. While CGP is increasingly used in low-middle income countries (LMIC), little is known about the extent to which these benefits patients. Here we describe the proportion of patients with advanced cancer in India who eventually receive targeted therapy for an actionable genetic alteration identified on CGP assays. Methods: This was a multicenter, retrospective cohort study in adult patients with advanced non-hematological malignancies who underwent a CGP test. We excluded patients who were identified to have a genetic alteration that has a well-validated targeted standard-of-care therapy (e.g.; EGFR exon 18, 19, 21 mutations for lung cancer, HER2 amplification for breast cancer). Participating oncologists provided anonymized information of consecutive CGP test reports through an online data capture form. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy. Results: During 2019-20, 12 medical oncologists provided CGP reports for 297 patients; 235 met the inclusion criteria. Fourteen different testing panels were used by the oncologists. Among the study cohort, 45% were male. Eighty nine percent underwent tumor tissue biopsy and 11% had liquid biopsy. The most common cancers were lung (19%), breast (18%), pancreatobiliary (9%) and colorectal (6%). Patients received a median of 2 lines (range: 0-5) of prior systemic therapy. Based on the CGP assay, 35 patients (15%) received targeted therapy. Among them, 29% was for HER2 amplification (non-breast cancer), 26% for PIK3CA mutation, 11% for HER2 or EGFR exon 20 insertion mutation (lung cancer), 5% each for BRAF mutation (non-melanoma), EGFR mutation (non-lung cancer) and MET mutation. Conclusions: In a LMIC setting, 15% patients received a targeted therapy based on CGP assay. This is comparable to reports from high income countries. Considering the limited access to new drugs and clinical trials, this finding requires further analysis.

scholarly journals Comprehensive Genomic Profiling-Guided Niraparib Treatment of Triple-Negative Breast Cancer in a Patient With Extensive Brain Metastasis: Case Report and Literature Review

2021 ◽  
Vol 4 (1) ◽  
pp. 16-20
Author(s):  
Tai-Chung Lam
Keyword(s):  
Breast Cancer ◽  
Clinical Response ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Single Agent ◽  
Gene Mutations ◽  
Central Nervous System Tumor ◽  
Genomic Profiling ◽  
Wild Type ◽  
Comprehensive Genomic Profiling

ABSTRACT Homologous recombination deficiency (HRD) is a common phenotypic alteration that is highly druggable with poly (ADP-ribose) polymerase inhibitors (PARPi). Although BRCA1/2 gene mutations are among the commonest genomic aberrations associated with HRD, defects in other DNA damage repair (DDR) genes also may influence clinical response to PARPi. Here, we report the case of a 51-year-old Chinese woman with extensive symptomatic brain metastases from metastatic BRCA1/2 wild-type triple-negative breast cancer (TNBC). Comprehensive genomic profiling (CGP) of resected central nervous system tumor revealed mutations in TP53 and multiple DDR pathway genes, suggesting an HRD phenotype. The patient showed a rapid and remarkable response to single-agent niraparib, and her improved condition remained stable for &gt; 8 weeks. To the best of our knowledge, this is the first report of the use of CGP for guiding targeted therapy with PARPi in patients with TNBC, for which options have been limited. CGP may have an increasingly impactful role to predict clinical response of PARPi in patients with BRCA1/2 wild-type TNBC.

Sign in / Sign up

Export Citation Format

Share Document