Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study

Kaboré, Elisé G.; Guenancia, Charles; Vaz-Luís, Inês; Meglio, Antonio Di; Pistilli, Barbara; Coutant, Charles; Cottu, Paul; Lesur, A.; Petit, Thierry; Dalenc, Florence; Rouanet, Philippe; Arnaud, Antoine; Arsène, Olivier; Ibrahim, Mohammed; Wassermann, Johanna; Boileau-Jolimoy, Geneviève; Martin, Anne‐Laure; Lemonnier, Jérôme; André, Fabrice; Arveux, Patrick

doi:10.1371/journal.pmed.1002989

Cited by 49 publications

(42 citation statements)

References 26 publications

(32 reference statements)

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“…A limitation of our study is that some patients may have been treated by their family physicians or referred to local hospitals, without any notification to ICH. Although no data was available to compare COVID-19 patients to the other breast cancer patients seen at ICH, rates of high BMI and hypertension in our COVID-19 patient cohort were very similar to those reported in a recent prospective large-scale report on French breast cancer patients [11], suggesting that these comorbidities do not increase the risk of COVID-19. Our analyses showed that breast cancer patients have similar clinical and radiologic features of COVID-19 to those previously described in other reports on non-cancer COVID-19 patients.…”

Section: Discussionsupporting

confidence: 81%

COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 81%

COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area

et al. 2020

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“…To the best of our knowledge, this is the first report on COVID-19 diagnosis, signs and outcome in breast cancer patients. [20], suggesting that these comorbidities do not increase the risk of COVID-19. Our analyses showed that breast cancer patients have similar clinical and radiologic features of COVID-19 to those previously described in other reports on non-cancer COVID-19 patients.…”

Section: Discussionmentioning

confidence: 98%

COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area

Vuagnat

Frélaut

Ramtohul

et al. 2020

Preprint

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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.

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“…Myocardial cell injuries are a hallmark of chemotherapy or targeted therapy-induced decompensated heart failure 43,44 . However, cellular proliferation or vitality of cardiomyocytes was not hampered on exposure to a PD-1 inhibitor in vitro.…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor induces cardiac injury through polarizing macrophages via modulating microRNA-34a/Kruppel-like factor 4 signaling

et al. 2020

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Cancer immunotherapy has become a well-established treatment option for some cancers; however, its use is hampered by its cardiovascular adverse effects. Immune checkpoint inhibitors (ICIs)-related cardiac toxicity took place in kinds of different forms, such as myocarditis, acute coronary syndrome, and pericardial disease, with high mortality rates. This study aimed to investigate the roles of programmed death-1 (PD-1) inhibitor, one of widespread used ICIs, in the development of murine cardiac injury. PD-1 inhibitor is known to transduce immunoregulatory signals that modulate macrophages polarization to attack tumor cells. Hence, this study explored whether the cardiovascular adverse effects of PD-1 inhibitor were related to macrophage polarization. MicroRNA-34a (miR-34a), which appears to regulate the polarization of cultured macrophages to induce inflammation, is examined in cardiac injury and macrophage polarization induced by the PD-1 inhibitor. As a target of miR-34a, Krüppel-like factor 4 (KLF4) acted as an anti-inflammation effector to take cardiac protective effect. Further, it investigated whether modulating the miR-34a/KLF4-signaling pathway could influence macrophage polarization. The PD-1 inhibitor markedly induced M1 phenotype macrophage polarization with impaired cardiac function, whereas miR-34a inhibitor transfection treatment reversed M1 polarization and cardiac injury in vivo. In vitro, PD-1 inhibitor-induced M1 polarization was accompanied by an increase in the expression of miR-34a but a decrease in the expression of KLF4. TargetScan and luciferase assay showed that miR-34a targeted the KLF4 3′-untranslated region. Either miR-34a inhibition or KLF4 overexpression could abolish M1 polarization induced by the PD-1 inhibitor. The findings strongly suggested that the PD-1 inhibitor exerted its effect in promoting M1 polarization and cardiac injury by modulating the miR-34a/KLF4-signaling pathway and inducing myocardial inflammation. These findings might help us to understand the pathogenesis of cardiac injury during immunotherapy, and provide new targets in ameliorating cardiac injury in patients with cancer receiving PD-1 inhibitor treatment.

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Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study

Cited by 49 publications

References 26 publications

COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area

COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area

COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area

Immune checkpoint inhibitor induces cardiac injury through polarizing macrophages via modulating microRNA-34a/Kruppel-like factor 4 signaling

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