scholarly journals Liquid Biopsy: New Tool to Overcome CDKi Resistance Mechanism in Luminal Metastatic Breast Cancer

2021 ◽  
Author(s):  
Miriam González-Conde ◽  
Celso Yanez ◽  
Rafael López-López ◽  
Clotilde Costa
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Hormone Receptors ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Luminal Breast Cancer ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women worldwide. Approximately, 70 % of breast cancer patients express hormone receptors (HR) (Luminal subtype). Adjuvant endocrine treatments are the standard of care in HR+/HER2- breast cancer. Over time, about 50% of those patients develop endocrine resistance and metastatic breast cancer. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacy increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic breast cancer patients. CDKi blocks kinases 4/6 ATP-binding domain preventing G1/S cell cycle transition. Despite this, not all patients respond to CDKi and those who respond, finally develop resistance to combination therapy. Different studies, in tumour tissue or cell lines, have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. In the last few years, liquid biopsy has contributed relevant information to this knowledge. Liquid biopsy can be performed in real-time, non-invasively and be repeated whenever needed. Circulating tumour material are potential prognostic markers in metastatic luminal breast cancer to determine patient prognosis, monitor disease and treatment selection. The objective of this review is to outline the different studies carried out in HR+ metastatic breast cancer patients treated with CDKi plus endocrine therapy using liquid biopsy approaches looking for possible resistance mechanisms.

scholarly journals Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Amanda Bortolini Silveira ◽  
François-Clément Bidard ◽  
Marie-Laure Tanguy ◽  
Elodie Girard ◽  
Olivier Trédan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Simultaneous Detection ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Breast Cancer Patients ◽  
Targeted Next Generation Sequencing ◽  
Patient Prognosis

AbstractCirculating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two cancer-derived blood biomarkers that inform on patient prognosis and treatment efficacy in breast cancer. We prospectively evaluated the clinical validity of quantifying both CTCs (CellSearch) and ctDNA (targeted next-generation sequencing). Their combined value as prognostic and early monitoring markers was assessed in 198 HER2-negative metastatic breast cancer patients. All patients were included in the prospective multicenter UCBG study COMET (NCT01745757) and treated by first-line chemotherapy with weekly paclitaxel and bevacizumab. Blood samples were obtained at baseline and before the second cycle of chemotherapy. At baseline, CTCs and ctDNA were respectively detected in 72 and 74% of patients and were moderately correlated (Kendall’s τ = 0.3). Only 26 (13%) patients had neither detectable ctDNA nor CTCs. Variants were most frequently observed in TP53 and PIK3CA genes. KMT2C/MLL3 variants detected in ctDNA were significantly associated with a lower CTC count, while the opposite trend was seen with GATA3 alterations. Both CTC and ctDNA levels at baseline and after four weeks of treatment were correlated with survival. For progression-free and overall survival, the best multivariate prognostic model included tumor subtype (triple negative vs other), grade (grade 3 vs other), ctDNA variant allele frequency (VAF) at baseline (per 10% increase), and CTC count at four weeks (≥5CTC/7.5 mL). Overall, this study demonstrates that CTCs and ctDNA have nonoverlapping detection profiles and complementary prognostic values in metastatic breast cancer patients. A comprehensive liquid-biopsy approach may involve simultaneous detection of ctDNA and CTCs.

scholarly journals Assessment of Survival and Cardiotoxicity of Adjuvant Trastuzumab among HER2 Breast Cancer Patients in an Oncology Centre in Malaysia

2018 ◽  
Vol 3 (1) ◽  
pp. 33
Author(s):  
Harissa Husainy Hasbullah ◽  
Anita Bustamam ◽  
Tho Lye Munn ◽  
Vincent Phua
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer

Introduction: Adjuvant trastuzumab has been used in human epidermal growth factor-2 (HER2) breast cancer to improve survival but with concern of cardiotoxicity. Our study is the first to review efficacy and toxicity of adjuvant trastuzumab in Malaysia. Methods: This is a retrospective cohort study on HER2 non metastatic breast cancer patients in University Malaya Medical Centre diagnosed between October 2006 and May 2011. Two cohorts were created based on whether or not they received adjuvant trastuzumab. Disease free survival (DFS) and overall survival (OS) for both groups were estimated using Kaplan Meier method and compared using Log rank test. Cox proportional hazards regression models analysed for potential covariates of age, tumour size and grade, node and estrogen receptor (ER) status. Trastuzumab cardiotoxicity was defined as left ventricular systolic dysfunction or heart failure with or without symptoms and graded using Common Terminology Criteria for Adverse Events (CTCAE 4.0). Results: 170 HER2 non metastatic breast cancer patients were identified. Thirty-three received trastuzumab and 136 did not. Median age was 53.4 ± 10.3 years old. Significantly more ER negative patients received trastuzumab. Four years DFS in ‘trastuzumab’ versus ‘no trastuzumab’ cohort was 90.9% vs 74.5% (p = 0.027). Four years OS was 91% vs 84.7% (p = 0.30) respectively. Majority tolerated trastuzumab with no toxicity. Five patients (15.2%) experienced cardiotoxicity (all grade I).Conclusions: Adjuvant trastuzumab significantly improved DFS in HER2 breast cancer. Treatment was well tolerated. With this we propose the justification for adjuvant trastuzumab in HER2 breast cancer in our population.

PI3K mutations detected in liquid biopsy are associated to reduced sensitivity to CDK4/6 inhibitors in metastatic breast cancer patients

2020 ◽  
pp. 105241
Author(s):  
Marzia Del Re ◽  
Stefania Crucitta ◽  
Giulia Lorenzini ◽  
Claudia De Angelis ◽  
Lucrezia Diodati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Metastatic Breast ◽  
Breast Cancer Patients

scholarly journals HER2 Expression in Circulating Tumour Cells Isolated from Metastatic Breast Cancer Patients Using a Size-Based Microfluidic Device

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4446
Author(s):  
Cláudia Lopes ◽  
Paulina Piairo ◽  
Alexandre Chícharo ◽  
Sara Abalde-Cela ◽  
Liliana R. Pires ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real Time ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Metastatic Breast ◽  
Tumour Cells ◽  
Circulating Tumour Cells ◽  
Breast Cancer Patients ◽  
Disease Evolution

HER2 is a prognostic and predictive biomarker in breast cancer, normally assessed in tumour biopsy and used to guide treatment choices. Circulating tumour cells (CTCs) escape the primary tumour and enter the bloodstream, exhibiting great metastatic potential and representing a real-time snapshot of the tumour burden. Liquid biopsy offers the unique opportunity for low invasive sampling in cancer patients and holds the potential to provide valuable information for the clinical management of cancer patients. This study assesses the performance of the RUBYchip™, a microfluidic system for CTC capture based on cell size and deformability, and compares it with the only FDA-approved technology for CTC enumeration, CellSearch®. After optimising device performance, 30 whole blood samples from metastatic breast cancer patients were processed with both technologies. The expression of HER2 was assessed in isolated CTCs and compared to tissue biopsy. Results show that the RUBYchipTM was able to isolate CTCs with higher efficiency than CellSearch®, up to 10 times more, averaging all samples. An accurate evaluation of different CTC subpopulations, including HER2+ CTCs, was provided. Liquid biopsy through the use of the RUBYchipTM in the clinic can overcome the limitations of histological testing and evaluate HER2 status in patients in real-time, helping to tailor treatment during disease evolution.

scholarly journals Investigation of the change in the biological structure of the tumor in metastatic breast cancer

2021 ◽  
Vol 8 (3) ◽  
pp. 171-174
Author(s):  
Veysel Haksoyler ◽  
Tolga Koseci ◽  
Timucin Cil ◽  
Berna Bozkurt Duman ◽  
Polat Olgun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Hormone Receptors ◽  
Tumor Biology ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Metastatic Site ◽  
Significant Difference ◽  
Her 2

Objective: When metastasis develops in some breast cancer patients, hormone receptors (HR) and Human Epidermal Growth Factor-2 (Her-2) status can change and the tumor alters its character. We tried to determine the rate of these changes in tumor biology in 110 patients that we followed in our clinic and performed the change of the biopsy from the metastatic site (re-bx). We aimed to determine the biological changes of tumors and, contribute to the literature by examining the relationship of these changes with the adjuvant endocrine treatments (ET) or chemotherapy type (CT). Material and Methods: We included 110 metastatic breast cancer patients in our study. These patients had previously completed their local treatments followed by CT, and those with positive HR completed ET. After the first metastasis developed in the patients, we performed metastasectomy or biopsy from the metastatic site. Results: The median ki-67 value was 25% at the time of primary diagnosis and 30% in re-bx. 20.9% of patients estrogen receptor (ER), 31.8%  of patients progesterone receptor (PR) and 26.3% of patients Her-2 changed when metastasis developed. Conclusions: We found that the metastatic tumor has more aggressive properties than the primary tumor. Adjuvant chemotherapy and endocrine treatments or the location of metastasis did not make a significant difference in tumor biology.

Budget impact analysis of the use of lapatinib in the treatment of breast cancer in Italy

2009 ◽  
Vol 10 (1) ◽  
pp. 33-46
Author(s):  
Francesco Bamfi ◽  
Federica Basso ◽  
Massimo Aglietta ◽  
Carmelo Bengala ◽  
Vito Lorusso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Budget Impact ◽  
Metastatic Breast ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
Number Of Patients ◽  
The Impact

Objective: to estimate the impact of lapatinib utilization within the Italian National Health Service (NHS) resources consumption. Lapatinib is an oral inhibitor of kinase protein, approved as dual therapy with capecitabine for the treatment of metastatic breast cancer patients with HER2 overexpression who experience disease progression despite trastuzumab treatment. Methods: the analysis is based on a model, which structure can be summarized as follows: a) national cancer registries-based estimate of the yearly number of HER2+ breast cancer patients who develop metastatic disease in Italy; b) literature-based identification of the rate of patients eligible to receive lapatinib; c) identification of the current therapeutic strategy-mix; d) costing of the alternatives, and e) calculation of budget impact. Direct NHS costs (drug acquisition and administration, and monitoring for 8 cycles of 21 days) are estimated based on current Italian prices and tariffs. Results: the annual number of patients eligible for lapatinib-based therapy can vary from 1,676 to 2,172, according to the expected extent of the trastuzumab use as adjuvant therapy. The current strategy-mix beyond progression is based on drugs used in the clinical practice, with a portion of patients continuing trastuzumab. Pharmaceutical cost of lapatinib results higher than the average cost of the current pattern of treatments. This cost increase would be partially offset by the reduction of laboratory tests and hospital personnel work for the oral administration of lapatinib, as compared to intravenous strategies. Furthermore, a risk sharing agreement has been adopted by NHS and manufacturer, according to which the NHS pays only for responding patients. As a consequence, lapatinib-based therapy would increase yearly NHS expenditure by about 3.8-4.9 millions of euro. Conclusions: lapatinib is the only treatment option specifically indicated for the management of HER2+, metastatic breast cancer in patients who received prior treatments including trastuzumab and is estimated to induce a low budget impact for the Italian NHS.

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