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.

scholarly journals Liquid biopsy in early breast cancer. A preliminary report

2019 ◽  
Author(s):  
ANTONIO RULLI ◽  
CINZIA ANTOGNELLI ◽  
ANNAMARIA SIGGILLINO ◽  
VINCENZO TALESA ◽  
ZAYIK SVITLANA ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Early Stage ◽  
Dynamic Monitoring ◽  
Molecular Profile ◽  
Precision Oncology ◽  
Surgical Biopsy ◽  
Post Surgery ◽  
Genetic Landscape

Abstract 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. 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.

Diagnosis and treatment monitoring in breast cancer: how liquid biopsy can support patient management

2022 ◽  
Author(s):  
Federico Cucchiara ◽  
Rosa Scarpitta ◽  
Stefania Crucitta ◽  
Cristian Scatena ◽  
Roberta Arici ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liquid Biopsy ◽  
Patient Management ◽  
Early Stage ◽  
Breast Cancer Diagnosis ◽  
Treatment Monitoring ◽  
Clinical Applications ◽  
Molecular Profile ◽  
Invasive Procedures

Imaging and tissue biopsies represent the current gold standard for breast cancer diagnosis and patient management. However, these practices are time-consuming, expensive and require invasive procedures. Moreover, tissue biopsies do not capture spatial and temporal tumor heterogeneity. Conversely, liquid biopsy, which includes circulating tumor cells, circulating free nucleic acids and extracellular vesicles, is minimally invasive, easy to perform and can be repeated during a patient's follow-up. Increasing evidence also suggests that liquid biopsy can be used to efficiently screen and diagnose tumors at an early stage, and to monitor changes in the tumor molecular profile. In the present review, clinical applications and prospects are discussed.

scholarly journals Potential Utility of Liquid Biopsy as a Diagnostic and Prognostic Tool for the Assessment of Solid Tumors: Implications in the Precision Oncology

2019 ◽  
Vol 8 (3) ◽  
pp. 373 ◽  
Author(s):  
Roshni Mathai ◽  
Ryali Vidya ◽  
B. Reddy ◽  
Levin Thomas ◽  
Karthik Udupa ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
The Body ◽  
Dynamic Monitoring ◽  
Precision Oncology ◽  
Clinical Implementation ◽  
Surgical Biopsy ◽  
Prognostic Tool ◽  
Specificity And Sensitivity

Liquid biopsy is a technique that utilizes circulating biomarkers in the body fluids of cancer patients to provide information regarding the genetic landscape of the cancer. It is emerging as an alternative and complementary diagnostic and prognostic tool to surgical biopsy in oncology. Liquid biopsy focuses on the detection and isolation of circulating tumor cells, circulating tumor DNA and exosomes, as a source of genomic and proteomic information in cancer patients. Liquid biopsy is expected to provide the necessary acceleratory force for the implementation of precision oncology in clinical settings by contributing an enhanced understanding of tumor heterogeneity and permitting the dynamic monitoring of treatment responses and genomic variations. However, widespread implementation of liquid biopsy based biomarker-driven therapy in the clinical practice is still in its infancy. Technological advancements have resolved many of the hurdles faced in the liquid biopsy methodologies but sufficient clinical and technical validation for specificity and sensitivity has not yet been attained for routine clinical implementation. This article provides a comprehensive review of the clinical utility of liquid biopsy and its effectiveness as an important diagnostic and prognostic tool in colorectal, breast, hepatocellular, gastric and lung carcinomas which were the five leading cancer related mortalities in 2018.

Liquid biopsy in the clinical management of hepatocellular carcinoma

Gut ◽  
2020 ◽  
Vol 69 (11) ◽  
pp. 2025-2034 ◽  
Author(s):  
Johann von Felden ◽  
Teresa Garcia-Lezana ◽  
Kornelius Schulze ◽  
Bojan Losic ◽  
Augusto Villanueva
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Response ◽  
Liquid Biopsy ◽  
Clinical Management ◽  
Early Stage ◽  
Personalised Medicine ◽  
Precision Oncology ◽  
Early Hepatocellular Carcinoma ◽  
Populations At Risk ◽  
Circulating Tumour Dna

With increasing knowledge on molecular tumour information, precision oncology has revolutionised the medical field over the past years. Liquid biopsy entails the analysis of circulating tumour components, such as circulating tumour DNA, tumour cells or tumour-derived extracellular vesicles, and has thus come as a handy tool for personalised medicine in many cancer entities. Clinical applications under investigation include early cancer detection, prediction of treatment response and molecular monitoring of the disease, for example, to comprehend resistance patterns and clonal tumour evolution. In fact, several tests for blood-based mutation profiling are already commercially available and have entered the clinical field.In the context of hepatocellular carcinoma, where access to tissue specimens remains mostly limited to patients with early stage tumours, liquid biopsy approaches might be particularly helpful. A variety of translational liquid biopsy studies have been carried out to address clinical needs, such as early hepatocellular carcinoma detection and prediction of treatment response. To this regard, methylation profiling of circulating tumour DNA has evolved as a promising surveillance tool for early hepatocellular carcinoma detection in populations at risk, which might soon transform the way surveillance programmes are implemented. This review summarises recent developments in the liquid biopsy oncological space and, in more detail, the potential implications in the clinical management of hepatocellular carcinoma. It further outlines technical peculiarities across liquid biopsy technologies, which might be helpful for interpretation by non-experts.

scholarly journals Dietary changes in early-stage breast cancer patients from pre-surgery and over the 12 months post-surgery

2020 ◽  
Vol 125 (2) ◽  
pp. 172-182
Author(s):  
Sonja H. Brunvoll ◽  
Inger Thune ◽  
Gro F. Bertheussen ◽  
Frøydis Fjeldheim ◽  
Vidar G. Flote ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Dairy Products ◽  
Early Stage ◽  
Processed Meat ◽  
Breast Cancer Patients ◽  
Food Diary ◽  
Dietary Changes ◽  
Post Surgery ◽  
Over Time

AbstractThe time after a breast cancer diagnosis is a potential period for making positive dietary changes, but previous results are conflicting. The main aim of the present study was to study breast cancer patients’ dietary changes during the 12 months post-surgery and from 12 months pre-surgery to 12 months post-surgery with repeated administration of a 7-d pre-coded food diary and an FFQ, respectively. Women (n 506), mean age 55·3 years diagnosed with invasive breast cancer (stages I and II), were included. The dietary intake was quite stable over time, but the intake was lower for energy (0·3 and 0·4 MJ/d), alcohol (1·9 and 1·5 g/d) and vegetables (17 and 22 g/d) at 6 months than 3 weeks post-surgery (food diary) and at 12 months post-surgery than pre-surgery (FFQ), respectively. Furthermore, energy percentage (E%) from carbohydrates increased between 0·8 and 1·2 E% and E% from fat decreased between 0·6 and 0·8 E% over time, measured by both dietary assessment methods. We observed a higher intake of dairy products (11 g/d) at 6 months post-surgery (food diary), and a lower intake of dairy products (34 g/d) and red and processed meat (7·2 g/d) at 12 months post-surgery (FFQ). Moreover, 24 % of the patients claimed they made dietary changes, but mostly they did not change their diet differently compared with those patients who claimed no changes. In conclusion, breast cancer patients reported only minor dietary changes from 12 months pre-surgery and during the 12 months post-surgery.

Abstract LB-226: Exosomal liquid biopsy reveals mRNA and lincRNA biomarkers in early stage breast cancer patient plasma

2018 ◽  
Author(s):  
Sudipto K. Chakrabortty ◽  
Robert R. Kitchen ◽  
Christine M. Coticchia ◽  
Vasisht R. Tadigotla ◽  
Erez Eitan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patient ◽  
Breast Cancer Patient ◽  
Liquid Biopsy ◽  
Early Stage ◽  
Early Stage Breast Cancer

The role of ado-trastuzumab emtansine in current clinical practice

2020 ◽  
pp. 107815522095186
Author(s):  
Alla Turshudzhyan
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Early Breast Cancer ◽  
Bystander Effect ◽  
Residual Disease ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Post Surgery ◽  
Her2 Breast Cancer ◽  
Randomized Controlled Studies

Objective This review reflects the literature from 2019 to 2020 on ado-trastuzumab emtansine’s (T-DM1) therapeutic use, clinical controversies, and newest perspectives on use. Data sources: PubMed was used as a database. Search “ado-trastuzumab emtansine” on June 11th, 2020 resulted in 57 publications: 20 clinical trials, two metanalysis, six randomized controlled studies, 13 reviews, and two systematic reviews. Of the 57 publications, 34 were descriptive of the topic in question and were used for this review. Data summary: T-DM1 is now used for patients with HER2 breast cancer who have residual disease post surgery after neoadjuvant chemotherapy (KATHERINE trial). Initial success prompted KRISTINE trial, which investigated whether T-DM1 can be used as a neoadjuvant therapy. While it did have fewer adverse events, T-DM1 was inferior to chemotherapy in treating early breast cancer. Noted shortcomings of the drug were toxicity limited Cmax, slow rate of internalization, lack of payload bystander effects, and number of resistance mechanisms. Proposed solutions were pre-treatment with metformin to augment drug internalization by the cell, use of second generation anti-HER2 antibody-drug conjugates to overcome developing resistance, payload swapping to increase bystander effect. Conclusions While T-DM1 has fewer side-effects, it is inferior to chemotherapy in early breast cancer treatment. More research should be done to overcome resistance pathways, identify rate-limiting intracellular processing pathways, improve bystander, and enhance internalization of the drug. Until more research is done, T-DM1 will continue to be used in HER2 positive breast cancer as well as a few other HER2 expressing tumors that fail to respond to neoadjuvant therapy.

scholarly journals Current Status of Circulating Tumor Cells, Circulating Tumor DNA, and Exosomes in Breast Cancer Liquid Biopsies

2020 ◽  
Vol 21 (24) ◽  
pp. 9457
Author(s):  
Marta Tellez-Gabriel ◽  
Erik Knutsen ◽  
Maria Perander
Keyword(s):  
Breast Cancer ◽  
Residual Disease ◽  
Early Stage ◽  
Clonal Evolution ◽  
Current Status ◽  
Primary Therapy ◽  
Liquid Biopsies ◽  
Diagnose Breast Cancer ◽  
Early Stage Disease ◽  
Cancer Management

Breast cancer is the most common cancer among women worldwide. Although the five-, ten- and fifteen-year survival rates are good for breast cancer patients diagnosed with early-stage disease, some cancers recur many years after completion of primary therapy. Tumor heterogeneity and clonal evolution may lead to distant metastasis and therapy resistance, which are the main causes of breast cancer-associated deaths. In the clinic today, imaging techniques like mammography and tissue biopsies are used to diagnose breast cancer. Even though these methods are important in primary diagnosis, they have limitations when it comes to longitudinal monitoring of residual disease after treatment, disease progression, therapy responses, and disease recurrence. Over the last few years, there has been an increasing interest in the diagnostic, prognostic, and predictive potential of circulating cancer-derived material acquired through liquid biopsies in breast cancer. Thanks to the development of sensitive devices and platforms, a variety of tumor-derived material, including circulating cancer cells (CTCs), circulating DNA (ctDNA), and biomolecules encapsulated in extracellular vesicles, can now be extracted and analyzed from body fluids. Here we will review the most recent studies on breast cancer, demonstrating the clinical potential and utility of CTCs and ctDNA. We will also review literature illustrating the potential of circulating exosomal RNA and proteins as future biomarkers in breast cancer. Finally, we will discuss some of the advantages and limitations of liquid biopsies and the future perspectives of this field in breast cancer management.

Sign in / Sign up

Export Citation Format

Share Document