The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper.

This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs.

Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs. In particular, this review will focus on breast, lung, colorectal and prostate cancer. Three major topics concerning the clinical utility of CTC are discussed-(1) treatment based on CTCs used as liquid biopsy, (2) treatment based on CTC count or CTC variations, and (3) treatment based on CTC biomarker expression. A summary of published or ongoing phase II and III trials is also presented.

Considerable interest surrounds the use of immune-checkpoint inhibitors in patients with solid tumours following the demonstration of the impressive clinical efficacy of anti-programmed cell death protein 1 and anti-programmed cell death 1 ligand 1 antibodies in several tumour types. However, the emergence of unexpected tumour response patterns, such as pseudoprogression or hyperprogression, might complicate the management of patients receiving these agents. Analysis of circulating tumour DNA (ctDNA) has been shown to have prognostic value by enabling the detection of residual proliferating disease in the adjuvant setting and estimation of tumour burden in the metastatic setting, which are key stratification biomarkers for use of immune-checkpoint inhibition (ICI). Furthermore, examinations of ctDNA for genetic predictors of responsiveness to immunotherapy, such as mutations, tumour mutational load, and microsatellite instability provide a noninvasive surrogate for tumour biopsy sampling. Proof-of-concept reports have also demonstrated that quantitative changes in ctDNA levels early in the course of disease are a promising tool for the assessment of responsiveness to ICI that might complement standard imaging approaches. Other applications of this technology are also currently under investigation, such as early detection of resistance to immunotherapy and characterization of mechanisms of resistance. The aim of this Review is to summarize available data on the application of ctDNA in patients receiving immunotherapy and to discuss the most promising future directions.

The transcription factor NRF2 (NFE2L2), regulates important antioxidant and cytoprotective genes. It enhances cancer cell proliferation and promotes chemoresistance in several cancers. Dimethyl fumarate (DMF) is known to promote NRF2 activity in noncancer models. We combined and methods to examine the effect of DMF on cancer cell death and the activation of the NRF2 antioxidant pathway. We demonstrated that at lower concentrations (<25 μmol/L), DMF has a cytoprotective role through activation of the NRF2 antioxidant pathway. At higher concentrations, however (>25 μmol/L), DMF caused oxidative stress and subsequently cytotoxicity in several cancer cell lines. High DMF concentration decreases nuclear translocation of NRF2 and production of its downstream targets. The pro-oxidative and cytotoxic effects of high concentration of DMF were abrogated by overexpression of NRF2 in OVCAR3 cells, suggesting that DMF cytotoxicity is dependent of NRF2 depletion. High concentrations of DMF decreased the expression of DJ-1, a NRF2 protein stabilizer. Using DJ-1 siRNA and expression vector, we observed that the expression level of DJ-1 controls NRF2 activation, antioxidant defenses, and cell death in OVCAR3 cells. Finally, antitumoral effect of daily DMF (20 mg/kg) was also observed in in two mice models of colon cancer. Taken together, these findings implicate the effect of DJ-1 on NRF2 in cancer development and identify DMF as a dose-dependent modulator of both NRF2 and DJ-1, which may be useful in exploiting the therapeutic potential of these endogenous antioxidants..

Background: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France).Methods: An IRB-approved prospective registry was set up at ICH on March 13 th , 2020 for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features and outcome. Data extraction was done on April 25 th , 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT-scan abnormalities.Results: Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed.Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N=41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (>70) were the two factors associated with a higher risk of intensive care unit admission and/or death. Conclusions:This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients.All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Background: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). Methods: An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities. Results: Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (> 70) were the two factors associated with a higher risk of intensive care unit admission and/or death.

IMPORTANCEThe choice between chemotherapy and endocrine therapy as first-line treatment for hormone receptor-positive, ERBB2 (also known as HER2)-negative metastatic breast cancer is usually based on the presence of clinical features associated with a poor prognosis. In this setting, a high circulating tumor cell (CTC) count (Ն5 CTCs/7.5 mL) is a strong adverse prognostic factor for overall survival and progression-free survival (PFS).OBJECTIVE To compare the efficacy of a clinician-driven treatment choice vs a CTC-driven choice for first-line treatment. INTERVENTIONSIn the CTC arm, patients received chemotherapy or endocrine therapy according to the CTC count (chemotherapy if Ն5 CTCs/7.5 mL; endocrine therapy if <5 CTCs/7.5 mL), whereas in the control arm, the choice was left to the investigator. DESIGN, SETTING, AND PARTICIPANTSIn the STIC CTC randomized, open-label, noninferiority phase 3 trial, participants were randomized to a clinician-driven choice of first-line treatment or a CTC count-driven first-line treatment choice. Eligible participants were premenopausal and postmenopausal women 18 years or older diagnosed with hormone receptor-positive, ERBB2-negative metastatic breast cancer. Data were collected at 17 French cancer centers