COVID-19 Prevention Guidance and the Incidence of Febrile Neutropenia in Breast Cancer Patients Receiving TAC Chemotherapy with Prophylactic Pegfilgrastim

COVID-19 Prevention Guidance and the Incidence of Febrile Neutropenia in Breast Cancer Patients Receiving TAC Chemotherapy with Prophylactic Pegfilgrastim | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article COVID-19 Prevention Guidance and the Incidence of Febrile Neutropenia in Breast Cancer Patients Receiving TAC Chemotherapy with Prophylactic Pegfilgrastim Hongki Gwak, Seung-Taek Lim, Ye-Won Jeon, Young-Jin J. Suh This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1588526/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Chemotherapy-induced febrile neutropenia (FN) is a medical emergency that can cause severe adverse effects and death. Respiratory infection is one of the main causes of FN. We studied whether infection prevention and control (IPC) guidance for COVID-19 reduces the incidence of FN. Methods We reviewed female breast cancer patients treated with adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) with prophylactic pegfilgrastim between 2019 and 2021. IPC guidance has been implemented since April 2020. Results There was no difference in the incidence of chemotherapy-induced neutropenia (CIN) between patients without and with IPC. In the IPC patients, the incidence of FN (9.5%), hospitalization duration (0.7 ± 1.5 days), and total hospital cost (279.6 ± 42.6 USD) were significantly lower than in non-IPC patients (27.9%, 2.0 ± 3.8 days and 364.7 ± 271.6 USD, respectively). Conclusion IPC guidance should be implemented to prevent FN in high-risk patients. COVID-19 infection prevention febrile neutropenia breast cancer Introduction Breast cancer is a systemic disease, and many breast cancer patients need chemotherapy in addition to oncological surgery and radiotherapy.[ 1 ] Dose-dense anthracycline/taxane- and docetaxel-based regimens are often used in breast cancer. According to international guidelines, the docetaxel, doxorubicin, and cyclophosphamide (TAC) regimen carries a high risk (> 20%) of chemotherapy-induced neutropenia (CIN) and its complications.[ 2 , 3 ] Patients with CIN may progress to febrile neutropenia (FN), which is a serious medical problem. TAC causes significantly more hematological adverse effects than other breast cancer chemotherapy regimens.[ 4 ] The use of prophylactic pegfilgrastim significantly reduced the incidence of CIN and FN in patients receiving TAC chemotherapy, although the rates were still high at 74–91.4% and 7–21.4%, respectively.[ 5 – 8 ] One of the main causes of fever in CIN patients is respiratory infection.[ 9 ] To prevent the spread of COVID-19, mask-wearing and physical distancing have been implemented. We investigated whether this COVID-19 infection prevention and control (IPC) guidance helped reduce the risk of FN in breast cancer patients receiving TAC chemotherapy. Methods Population This was a single-center retrospective observational study. The study protocol was approved by the institutional review board of the Catholic University of Korea (VC22RASI0019). Electronic medical records of female breast cancer patients who received adjuvant TAC chemotherapy with prophylactic pegfilgrastim from January 2019 to December 2021, at St. Vincent’s Hospital of the Catholic University of Korea, were reviewed. Patients were excluded if they were pregnant or taking immunosuppressive drugs, had previously received other chemotherapy, had abnormal hematopoietic, liver, renal, or cardiac function before the chemotherapy, or had an Eastern Cooperative Oncology Group (ECOG) score of ≥ 2. Data collection Variables extracted from the database included patient demographics, ECOG performance status, characteristics of the cancer [histological type and grade, stage, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), surgery type, radiation therapy], laboratory results, and infectious diseases. ER and PR status, as determined using enzyme immunoassays, was obtained from the medical records. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), or silver in situ hybridization (SISH) was used to evaluate HER2 status. Samples with an IHC score of 0 or + 1, or an IHC score of + 2 and negative FISH/SISH, were considered negative for HER2 overexpression. Data were collected between the start of chemotherapy and 2 months thereafter. Treatment The chemotherapy consisted of doxorubicin (50 mg/m 2 ), cyclophosphamide (500 mg/m 2 ), and docetaxel (75 mg/m 2 ), administered on day 1 (and every 3 weeks thereafter). Pegfilgrastim 0.6 mL was administered subcutaneously 24–48 hours later. Laboratory tests, including complete blood count (CBC) with differential and biochemistry assays, were performed before each chemotherapy cycle and on day 6. After chemotherapy, the CBC was measured from day 6 until the absolute neutrophil count returned to 1,000/mm 3 . All patients with grade 4 CIN received prophylactic antibiotic therapy comprising 2 g intravenous cefoperazone and 200 mg tobramycin sulfate once daily, unless their use was contraindicated. Definitions ECOG performance status describes a patient’s level of function and self-care capability.[ 10 ] It ranges from 0 to 5, with 0 indicating an active person able to carry out all pre-disease activities without restriction, and 5 indicating death. Each patient’s performance status was evaluated before the first chemotherapy cycle. The adverse events of interest were based on the Common Terminology Criteria for Adverse Events (ver. 6.0). FN was defined as neutropenia (< 500 neutrophils/µL or < 1,000 neutrophils/µL for over 48 hours) with a febrile event (oral temperature ≥ 38.3°C or ≥ 38.0°C for over 1 hour) observed by medical staff. Dose reduction was defined as a reduction in the delivered dose of any agent relative to the standard values. The total hospital cost was the sum of all medical expenses paid to the hospital during the data collection period. Outpatient hospital visit, hospitalization, and chemotherapy costs, and the costs of all devices and drugs used for medical purposes, were included in the total hospital cost. IPC guidance to prevent COVID-19 infection includes good personal hygiene, prioritizing handwashing, cleaning high-touch surfaces such as mobile phones regularly or as needed, covering the mouth when coughing and sneezing, and wearing masks. Social distancing involves staying at least 2 meters away from others, avoiding poorly ventilated spaces and crowds, and following work and quarantine restrictions.[ 11 ] There are three levels of social distancing, implemented according to the number of patients diagnosed with COVID-19.[ 12 ] IPC guidance has been implemented since April 2020. Statistical analysis The chi-square test was used to compare categorical variables. Standardized residuals were analyzed for variables with more than two categories. Student’s t -test was used for analyzing continuous variables. To identify independent risk factors for FN, multivariate logistic regression including variables significant in the univariate analyses was performed. The analyses were performed using R software (ver. 4.0.2, R Core Team, 2013). Results Of the 85 chemotherapy patients, IPC was applied for 43, but not for the remaining 42. The mean age of the two groups was 53.7 and 52.3 years, respectively ( p > 0.05). Significantly more patients in the non-IPC group were ER-positive (72.7% vs . 52.4%). Table 1 summarizes the characteristics of the patients in each group. All included patients had an ECOG score of 0 and none had COVID-19 infection during the follow-up period. Grade 4 CIN occurred in 93.0% (40/43) of the non-IPC group and 90.5% (38/42) of the IPC group ( p = 0.713). FN occurred significantly less often in the IPC group (9.5% vs . 27.9%; p = 0.050). The duration of hospitalization, hospitalization cost, and total hospital cost were significantly lower in the IPC group. There were no significant group differences in adverse effects, including anemia, thrombocytopenia, liver or renal function abnormality, and transfusion. There was also no group difference in the dose reduction or delay of chemotherapy (Table 2 ). Of the 14 patients who developed FN, 2 (12.5%) died of sepsis during the observation period. All deaths were in the non-IPC group, but there was no statistical difference compared to the IPC group. The factors that differed significantly between the groups in the univariate logistic regression analysis of FN development were IPC and comorbidities (Table 3 ). Multivariate logistic regression analysis revealed that both factors were independently associated with an increased likelihood of FN development (odds ratio/95% confidence interval: 4.668/1.238–17.602 and 5.554/1.294–23.843, respectively) (Table 4 ). Table 1 Patient demographics and tumor characteristics COVID-19 prevention and control No (n = 43) Yes (n = 42) p -value Age (years) 52.3 ± 8.3 53.7 ± 8.6 0.452 BMI (kg/m 2 ) 24.8 ± 3.6 24.7 ± 3.7 0.924 BSA (m 2 ) 1.6 ± 0.1 1.6 ± 0.1 0.962 Age (years) < 60 ≥ 60 33 (76.7) 10 (23.3) 28 (66.7) 14 (33.3) 0.342 Type of surgery BCS Mastectomy 39 (90.7) 4 (9.3) 41 (97.6) 1 (2.4) 0.360 T stage I II III, IV 26 (60.5) 15 (34.9) 2 (4.7) 16 (38.1) 25 (59.5) 1 (2.4) 0.074 N stage 0 I II, III 7 (16.3) 27 (62.8) 9 (20.9) 9 (21.4) 19 (45.2) 14 (33.3) 0.257 Histological type IDC ILC Others 37 (86.0) 2 (4.7) 4 (9.3) 34 (81.0) 1 (2.4) 7 (16.7) 0.531 Histologic grade G1, G2 G3 28 (65.1) 15 (34.9) 17 (42.9) 24 (57.1) 0.051 Estrogen receptor Positive Negative 33 (76.7) 10 (23.3) 22 (52.4) 20 (47.6) 0.024 Progesterone receptor Positive Negative 18 (41.9) 25 (58.1) 12 (28.6) 30 (71.4) 0.258 HER2 Positive Negative 8 (18.6) 35 (81.4) 11 (26.2) 31 (73.8) 0.444 Comorbidity No HTN DM HTN + DM 38 (88.4) 1 (2.3) 2 (4.7) 2 (4.7) 35 (83.3) 6 (14.3) 0 (0.0) 1 (2.4) 0.111 Smoking Yes No 0 (0) 43 (100) 1 (2.4) 41 (97.6) 0.494 Data are expressed as n (%) BMI, body mass index; BSA, body surface area; DM, diabetes mellitus, HER2, human epidermal growth factor receptor 2; HTN, hypertension Table 2 Incidence of chemotherapy-related adverse events and hospital costs COVID-19 prevention and control No (n = 43) Yes (n = 42) p -value Neutropenia (grade 3 or 4) 43 (100) 40 (95.2) 0.241 Neutropenia (grade 4) 40 (93.0%) 38 (90.5) 0.713 FN 12 (27.9%) 4 (9.5%) 0.050 Admission 17 (39.5) 9 (21.4%) 0.099 Hospitalization duration (days) 2.0 ± 3.8 0.7 ± 1.5 0.041 Outpatient costs (USD) 227.0 ± 166.7 253.8 ± 58.7 0.325 Inpatient costs (USD) 137.7 ± 186.4 26.4 ± 60.1 0.001 Total cost (USD) 364.7 ± 271.6 279.6 ± 42.6 0.049 Dose reduction or delay 7 (16.3) 3 (7.1) 0.313 Anemia 3 (7.0) 1 (2.4) 0.616 Thrombocytopenia 8 (18.6) 6 (14.3) 0.771 Liver function abnormality 5 (11.6%) 7 (16.7) 0.549 Renal failure 1 (2.3) 0 (0) 1.000 Transfusion 4 (9.3) 2 (4.8) 0.676 Infection 5 (11.6) 4 (9.5) 1.000 Death 2 (4.7) 0 0.494 Data are expressed as number (%) Table 3 Odds of febrile neutropenia according to logistic regression analysis Variable OR 95% Confidence interval p -value Age (years) < 60 ≥ 60 1 1.700 0.540–5.347 0.364 Menopause Premenopausal menopausal 1 0.947 0.307–2.917 0.924 BMI (kg/m 2 ) < 25 ≥ 25 1 0.688 0.248–1.903 0.471 IPC guidance Yes No 1 3.677 1.078–12.543 0.038 Comorbidities No Yes 1 4.026 1.081–14.990 0.038 Histologic type IDC ILC Others 1 2.231 0.991 0.188–26.496 0.191–5.142 0.525 0.992 T stage T1 T2 T3–T4 1 0.524 7.333 0.159–1.726 0.595–90.332 0.288 0.120 N stage 0 1 2 3 1 2.545 2.154 1.400 0.503–12–891 0.336–13.804 0.103–19.012 0.259 0.418 0.800 Estrogen receptor Negative Positive 1 1.268 0.426–3.775 0.669 Progesterone receptor Negative Positive 1 0.610 0.195–1.905 0.395 HER2 Negative Positive 1 1.301 0.400–4.234 0.662 BMI, body mass index; BSA, body surface area; DM, diabetes mellitus, HER2, human epidermal growth factor receptor 2; IPC, infection prevention and control Table 4 Odds of febrile neutropenia according to multivariate logistic regression analysis Variable OR 95% Confidence interval p -value IPC guidance Yes No 1 4.668 1.238–17.602 0.023 Comorbidities No Yes 1 5.554 1.294–23.843 0.021 IPC, infection prevention and control Discussion The three chemotherapy regimens most frequently used in breast cancer patients with axillary lymph node metastasis are AC-T (doxorubicin, cyclophosphamide, docetaxel), AT (doxorubicin, paclitaxel), and TAC. According to the National Comprehensive Cancer Network (NCCN) guidelines, all three regimens pose a high risk of neutropenia and its complications (> 20%).[ 3 ] Our study focused on the TAC regimen, which was the most likely to show the prophylactic effect of IPC due to the high incidence of FN. Six-cycle TAC has the advantage of similar efficacy, but with a shorter treatment period, than eight-cycle AC followed by docetaxel.[ 13 ] However, the TAC regimen has a very high rate of FN, with CIN occurring in 100% of patients receiving TAC chemotherapy and FN in 42.5–63.4%.[ 8 , 14 ] In our study, 97.6% patients developed CIN and 18.8% developed FN. Chemotherapy-induced FN is a severe adverse effect that can delay the chemotherapy schedule, reduce the relative dose intensity, and increase the hospitalization period, which increases costs.[ 15 , 16 ] In addition, FN can cause life-threatening infections, with fatality rates of 5–11%.[ 16 ] The mortality rate of FN in our study was 12.5% (2/14), and there was no death in the IPC group. Risk factors for FN include age, performance status, gender, comorbidities, laboratory abnormalities, BMI, chemotherapy regimen, neutropenia prophylaxis, tumor type, disease progression, and genetic risk factors.[ 17 ] In this study, these factors were controlled or analyzed, and only IPC and comorbidity were independently related to the development of FN. The use of prophylactic G-CSF improves the prognosis of patients on the TAC regimen by lowering the incidence and duration of FN.[ 15 ] The NCCN, American Society of Clinical Oncology, and European Organization for the Research and Treatment of Cancer guidelines recommend routine use of primary G-CSF prophylaxis for high-risk cases (risk of FN > 20%) based on several randomized controlled trials.[ 18 – 20 ] The use of prophylactic ciprofloxacin can also lower the incidence of FN.[ 5 ] Despite these efforts, however, the rates of FN and its complications are still high.[ 5 – 8 ] In addition, the side effects of these prophylactic drugs cannot be ignored. Ciprofloxacin can cause pancytopenia and G-CSF is associated with the development of acute myeloid leukemia.[ 21 , 22 ] In comparison, mask wearing and physical distancing are free from the potential risks of various pharmaceutical preventive methods. All patients in this study had an ECOG score of 0, and received primary prophylactic pegfilgrastim to prevent FN and its complications, as well as prophylactic antibiotics when grade 4 NIC developed. The patients received all of these prophylactic drugs, and additional IPC significantly reduced the FN incidence rate, hospitalization duration, and hospital costs. One of the main causes of fever in CIN patients is respiratory infection, which has a high mortality rate. Most respiratory infections in FN are bacterial or fungal, which can be controlled to some extent with drugs. However, viruses are also a cause, and one study detected a virus in 41% of patients.[ 9 , 23 ] After the COVID-19 outbreak, the World Health Organization and Centers for Disease Control promoted mask wearing and physical distancing. This prevention guidance has proven effective against the transmission of respiratory diseases.[ 12 , 24 , 25 ] Our study showed that these guidelines were also effective in reducing the likelihood of FN in patients receiving TAC. There were limitations to this study. First, it was retrospective. However, it was conducted under conditions controlled by the state due to the pandemic, it should have higher reliability than other retrospective studies. Second, the number of patients was insufficient for a single-center study. However, the TAC regimen has a high incidence of FN and the preventive effect of IPC was better than expected; significant results were obtained despite the small study population. Conclusions IPC reduces the occurrence of FN and reduces hospitalization duration and costs. It should be performed during chemotherapy in all patients at high risk of developing FN. Statements And Declarations Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Ye-Won Jeon], [Hongki Gwak] and [Young-Jin Suh]. The first draft of the manuscript was written by [HG] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Ye-Won Jeon], [Hongki Gwak] and [Young-Jin Suh]. The first draft of the manuscript was written by [HG] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the institutional review board of the Catholic University of Korea (27-February-2022 / VC22RASI0019) Consent to participate Institutional Review Board waived the informed consent for this retrospective study. Consent to publish Institutional Review Board waived the informed consent for this retrospective study. 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For a certificate, please see: http://www.textcheck.com/certificate/IoPhn0 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1588526","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":101331581,"identity":"3c482a0e-5eb7-4f6e-a7c0-dc5643082503","order_by":0,"name":"Hongki Gwak","email":"","orcid":"","institution":"St. Vincent’s Hospital, The Catholic University of Korea","correspondingAuthor":false,"prefix":"","firstName":"Hongki","middleName":"","lastName":"Gwak","suffix":""},{"id":101331582,"identity":"abc5ade8-cf5a-4b67-99a5-eff8c36bbd5d","order_by":1,"name":"Seung-Taek Lim","email":"","orcid":"","institution":"St. Vincent’s Hospital, The Catholic University of Korea","correspondingAuthor":false,"prefix":"","firstName":"Seung-Taek","middleName":"","lastName":"Lim","suffix":""},{"id":101331583,"identity":"15b0e7cb-a055-46be-afdf-9470c9d1ec1b","order_by":2,"name":"Ye-Won Jeon","email":"","orcid":"","institution":"St. Vincent’s Hospital, The Catholic University of Korea","correspondingAuthor":false,"prefix":"","firstName":"Ye-Won","middleName":"","lastName":"Jeon","suffix":""},{"id":101331584,"identity":"7004acb9-77d8-4cc3-9ac3-5d9954c305f4","order_by":3,"name":"Young-Jin J. Suh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIie3RLQvCQBzH8d8YnGXTOjlhvoTJwOLD3srGgcliMywMBC2D1QniazCZ/zKYZS9gYNFiNhqdosFyLhruW+6B+8AdB6hUfxlBx7waLWjkv3ZYHVIAhlVNaxJA15ZvgjrEORyvfLYd2x5fEJ1D2K2ITW5SQkWfr/eiF3dyn/wcvZRYlv4gjJt70mJr6lAQQduhsZBfjKqLmRvyPsSrQajPzYiCDwl2YJmUtKlwB0YuRFxOnm+xRJoxISXN8ng5GeF4tErF4XIPh6NktXSlpFvS17r6HV0KADuJfpxQqVQq1QNyVEwmtR8wqwAAAABJRU5ErkJggg==","orcid":"","institution":"St. Vincent’s Hospital, The Catholic University of Korea","correspondingAuthor":true,"prefix":"","firstName":"Young-Jin","middleName":"J.","lastName":"Suh","suffix":""}],"badges":[],"createdAt":"2022-04-24 01:14:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1588526/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1588526/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":27408051,"identity":"65617aed-aeb8-465e-a92f-7ea5f2d97263","added_by":"auto","created_at":"2022-10-06 07:44:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":287068,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1588526/v1/c79eff7d-f7ac-48f2-864b-b92ceacb8c8c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"COVID-19 Prevention Guidance and the Incidence of Febrile Neutropenia in Breast Cancer Patients Receiving TAC Chemotherapy with Prophylactic Pegfilgrastim","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer is a systemic disease, and many breast cancer patients need chemotherapy in addition to oncological surgery and radiotherapy.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Dose-dense anthracycline/taxane- and docetaxel-based regimens are often used in breast cancer. According to international guidelines, the docetaxel, doxorubicin, and cyclophosphamide (TAC) regimen carries a high risk (\u0026gt;\u0026thinsp;20%) of chemotherapy-induced neutropenia (CIN) and its complications.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003cp\u003ePatients with CIN may progress to febrile neutropenia (FN), which is a serious medical problem. TAC causes significantly more hematological adverse effects than other breast cancer chemotherapy regimens.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] The use of prophylactic pegfilgrastim significantly reduced the incidence of CIN and FN in patients receiving TAC chemotherapy, although the rates were still high at 74\u0026ndash;91.4% and 7\u0026ndash;21.4%, respectively.[\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOne of the main causes of fever in CIN patients is respiratory infection.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] To prevent the spread of COVID-19, mask-wearing and physical distancing have been implemented. We investigated whether this COVID-19 infection prevention and control (IPC) guidance helped reduce the risk of FN in breast cancer patients receiving TAC chemotherapy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePopulation\u003c/h2\u003e \u003cp\u003eThis was a single-center retrospective observational study. The study protocol was approved by the institutional review board of the Catholic University of Korea (VC22RASI0019). Electronic medical records of female breast cancer patients who received adjuvant TAC chemotherapy with prophylactic pegfilgrastim from January 2019 to December 2021, at St. Vincent\u0026rsquo;s Hospital of the Catholic University of Korea, were reviewed. Patients were excluded if they were pregnant or taking immunosuppressive drugs, had previously received other chemotherapy, had abnormal hematopoietic, liver, renal, or cardiac function before the chemotherapy, or had an Eastern Cooperative Oncology Group (ECOG) score of \u0026ge;\u0026thinsp;2.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eVariables extracted from the database included patient demographics, ECOG performance status, characteristics of the cancer [histological type and grade, stage, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), surgery type, radiation therapy], laboratory results, and infectious diseases. ER and PR status, as determined using enzyme immunoassays, was obtained from the medical records. Immunohistochemistry (IHC), fluorescence \u003cem\u003ein situ\u003c/em\u003e hybridization (FISH), or silver \u003cem\u003ein situ\u003c/em\u003e hybridization (SISH) was used to evaluate HER2 status. Samples with an IHC score of 0 or +\u0026thinsp;1, or an IHC score of +\u0026thinsp;2 and negative FISH/SISH, were considered negative for HER2 overexpression. Data were collected between the start of chemotherapy and 2 months thereafter.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eTreatment\u003c/h2\u003e \u003cp\u003eThe chemotherapy consisted of doxorubicin (50 mg/m\u003csup\u003e2\u003c/sup\u003e), cyclophosphamide (500 mg/m\u003csup\u003e2\u003c/sup\u003e), and docetaxel (75 mg/m\u003csup\u003e2\u003c/sup\u003e), administered on day 1 (and every 3 weeks thereafter). Pegfilgrastim 0.6 mL was administered subcutaneously 24\u0026ndash;48 hours later. Laboratory tests, including complete blood count (CBC) with differential and biochemistry assays, were performed before each chemotherapy cycle and on day 6. After chemotherapy, the CBC was measured from day 6 until the absolute neutrophil count returned to 1,000/mm\u003csup\u003e3\u003c/sup\u003e. All patients with grade 4 CIN received prophylactic antibiotic therapy comprising 2 g intravenous cefoperazone and 200 mg tobramycin sulfate once daily, unless their use was contraindicated.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eDefinitions\u003c/h2\u003e \u003cp\u003eECOG performance status describes a patient\u0026rsquo;s level of function and self-care capability.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] It ranges from 0 to 5, with 0 indicating an active person able to carry out all pre-disease activities without restriction, and 5 indicating death. Each patient\u0026rsquo;s performance status was evaluated before the first chemotherapy cycle. The adverse events of interest were based on the Common Terminology Criteria for Adverse Events (ver. 6.0).\u003c/p\u003e \u003cp\u003eFN was defined as neutropenia (\u0026lt;\u0026thinsp;500 neutrophils/\u0026micro;L or \u0026lt;\u0026thinsp;1,000 neutrophils/\u0026micro;L for over 48 hours) with a febrile event (oral temperature\u0026thinsp;\u0026ge;\u0026thinsp;38.3\u0026deg;C or \u0026ge;\u0026thinsp;38.0\u0026deg;C for over 1 hour) observed by medical staff. Dose reduction was defined as a reduction in the delivered dose of any agent relative to the standard values. The total hospital cost was the sum of all medical expenses paid to the hospital during the data collection period. Outpatient hospital visit, hospitalization, and chemotherapy costs, and the costs of all devices and drugs used for medical purposes, were included in the total hospital cost.\u003c/p\u003e \u003cp\u003eIPC guidance to prevent COVID-19 infection includes good personal hygiene, prioritizing handwashing, cleaning high-touch surfaces such as mobile phones regularly or as needed, covering the mouth when coughing and sneezing, and wearing masks. Social distancing involves staying at least 2 meters away from others, avoiding poorly ventilated spaces and crowds, and following work and quarantine restrictions.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] There are three levels of social distancing, implemented according to the number of patients diagnosed with COVID-19.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] IPC guidance has been implemented since April 2020.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe chi-square test was used to compare categorical variables. Standardized residuals were analyzed for variables with more than two categories. Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test was used for analyzing continuous variables. To identify independent risk factors for FN, multivariate logistic regression including variables significant in the univariate analyses was performed. The analyses were performed using R software (ver. 4.0.2, R Core Team, 2013).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOf the 85 chemotherapy patients, IPC was applied for 43, but not for the remaining 42. The mean age of the two groups was 53.7 and 52.3 years, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Significantly more patients in the non-IPC group were ER-positive (72.7% \u003cem\u003evs\u003c/em\u003e. 52.4%). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the characteristics of the patients in each group. All included patients had an ECOG score of 0 and none had COVID-19 infection during the follow-up period.\u003c/p\u003e \u003cp\u003eGrade 4 CIN occurred in 93.0% (40/43) of the non-IPC group and 90.5% (38/42) of the IPC group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.713). FN occurred significantly less often in the IPC group (9.5% \u003cem\u003evs\u003c/em\u003e. 27.9%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.050). The duration of hospitalization, hospitalization cost, and total hospital cost were significantly lower in the IPC group. There were no significant group differences in adverse effects, including anemia, thrombocytopenia, liver or renal function abnormality, and transfusion. There was also no group difference in the dose reduction or delay of chemotherapy (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Of the 14 patients who developed FN, 2 (12.5%) died of sepsis during the observation period. All deaths were in the non-IPC group, but there was no statistical difference compared to the IPC group.\u003c/p\u003e \u003cp\u003eThe factors that differed significantly between the groups in the univariate logistic regression analysis of FN development were IPC and comorbidities (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Multivariate logistic regression analysis revealed that both factors were independently associated with an increased likelihood of FN development (odds ratio/95% confidence interval: 4.668/1.238\u0026ndash;17.602 and 5.554/1.294\u0026ndash;23.843, respectively) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient demographics and tumor characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCOVID-19 prevention and control\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.452\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.924\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBSA (m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.962\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60\u003c/p\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (76.7)\u003c/p\u003e \u003cp\u003e10 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (66.7)\u003c/p\u003e \u003cp\u003e14 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.342\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of surgery\u003c/p\u003e \u003cp\u003eBCS\u003c/p\u003e \u003cp\u003eMastectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (90.7)\u003c/p\u003e \u003cp\u003e4 (9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (97.6)\u003c/p\u003e \u003cp\u003e1 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.360\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT stage\u003c/p\u003e \u003cp\u003eI\u003c/p\u003e \u003cp\u003eII\u003c/p\u003e \u003cp\u003eIII, IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (60.5)\u003c/p\u003e \u003cp\u003e15 (34.9)\u003c/p\u003e \u003cp\u003e2 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (38.1)\u003c/p\u003e \u003cp\u003e25 (59.5)\u003c/p\u003e \u003cp\u003e1 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.074\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN stage\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003eI\u003c/p\u003e \u003cp\u003eII, III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (16.3)\u003c/p\u003e \u003cp\u003e27 (62.8)\u003c/p\u003e \u003cp\u003e9 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (21.4)\u003c/p\u003e \u003cp\u003e19 (45.2)\u003c/p\u003e \u003cp\u003e14 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistological type\u003c/p\u003e \u003cp\u003eIDC\u003c/p\u003e \u003cp\u003eILC\u003c/p\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (86.0)\u003c/p\u003e \u003cp\u003e2 (4.7)\u003c/p\u003e \u003cp\u003e4 (9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (81.0)\u003c/p\u003e \u003cp\u003e1 (2.4)\u003c/p\u003e \u003cp\u003e7 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.531\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistologic grade\u003c/p\u003e \u003cp\u003eG1, G2\u003c/p\u003e \u003cp\u003eG3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (65.1)\u003c/p\u003e \u003cp\u003e15 (34.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (42.9)\u003c/p\u003e \u003cp\u003e24 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEstrogen receptor\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (76.7)\u003c/p\u003e \u003cp\u003e10 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (52.4)\u003c/p\u003e \u003cp\u003e20 (47.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgesterone receptor\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (41.9)\u003c/p\u003e \u003cp\u003e25 (58.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (28.6)\u003c/p\u003e \u003cp\u003e30 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.258\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHER2\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (18.6)\u003c/p\u003e \u003cp\u003e35 (81.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (26.2)\u003c/p\u003e \u003cp\u003e31 (73.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.444\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidity\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eHTN\u003c/p\u003e \u003cp\u003eDM\u003c/p\u003e \u003cp\u003eHTN\u0026thinsp;+\u0026thinsp;DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (88.4)\u003c/p\u003e \u003cp\u003e1 (2.3)\u003c/p\u003e \u003cp\u003e2 (4.7)\u003c/p\u003e \u003cp\u003e2 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (83.3)\u003c/p\u003e \u003cp\u003e6 (14.3)\u003c/p\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003cp\u003e1 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003cp\u003e43 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4)\u003c/p\u003e \u003cp\u003e41 (97.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.494\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are expressed as n (%)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBMI, body mass index; BSA, body surface area; DM, diabetes mellitus, HER2, human epidermal growth factor receptor 2; HTN, hypertension\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIncidence of chemotherapy-related adverse events and hospital costs\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCOVID-19 prevention and control\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutropenia (grade 3 or 4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (95.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.241\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutropenia (grade 4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (93.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (90.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.713\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (27.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.050\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdmission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (39.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization duration (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutpatient costs (USD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e227.0\u0026thinsp;\u0026plusmn;\u0026thinsp;166.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e253.8\u0026thinsp;\u0026plusmn;\u0026thinsp;58.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.325\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInpatient costs (USD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e137.7\u0026thinsp;\u0026plusmn;\u0026thinsp;186.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.4\u0026thinsp;\u0026plusmn;\u0026thinsp;60.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal cost (USD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e364.7\u0026thinsp;\u0026plusmn;\u0026thinsp;271.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e279.6\u0026thinsp;\u0026plusmn;\u0026thinsp;42.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDose reduction or delay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (16.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.313\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.616\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (18.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.771\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver function abnormality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (11.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.549\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.676\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.494\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData are expressed as number (%)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOdds of febrile neutropenia according to logistic regression analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% Confidence interval\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60\u003c/p\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1.700\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.540\u0026ndash;5.347\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMenopause\u003c/p\u003e \u003cp\u003ePremenopausal\u003c/p\u003e \u003cp\u003emenopausal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0.947\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.307\u0026ndash;2.917\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.924\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25\u003c/p\u003e \u003cp\u003e\u0026ge;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0.688\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.248\u0026ndash;1.903\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.471\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIPC guidance\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e3.677\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.078\u0026ndash;12.543\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidities\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e4.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.081\u0026ndash;14.990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistologic type\u003c/p\u003e \u003cp\u003eIDC\u003c/p\u003e \u003cp\u003eILC\u003c/p\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2.231\u003c/p\u003e \u003cp\u003e0.991\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.188\u0026ndash;26.496\u003c/p\u003e \u003cp\u003e0.191\u0026ndash;5.142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.525\u003c/p\u003e \u003cp\u003e0.992\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT stage\u003c/p\u003e \u003cp\u003eT1\u003c/p\u003e \u003cp\u003eT2\u003c/p\u003e \u003cp\u003eT3\u0026ndash;T4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0.524\u003c/p\u003e \u003cp\u003e7.333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.159\u0026ndash;1.726\u003c/p\u003e \u003cp\u003e0.595\u0026ndash;90.332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.288\u003c/p\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN stage\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2.545\u003c/p\u003e \u003cp\u003e2.154\u003c/p\u003e \u003cp\u003e1.400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.503\u0026ndash;12\u0026ndash;891\u003c/p\u003e \u003cp\u003e0.336\u0026ndash;13.804\u003c/p\u003e \u003cp\u003e0.103\u0026ndash;19.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.259\u003c/p\u003e \u003cp\u003e0.418\u003c/p\u003e \u003cp\u003e0.800\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEstrogen receptor\u003c/p\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1.268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.426\u0026ndash;3.775\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.669\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgesterone receptor\u003c/p\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0.610\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.195\u0026ndash;1.905\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.395\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHER2\u003c/p\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1.301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.400\u0026ndash;4.234\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.662\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBMI, body mass index; BSA, body surface area; DM, diabetes mellitus, HER2, human epidermal growth factor receptor 2; IPC, infection prevention and control\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOdds of febrile neutropenia according to multivariate logistic regression analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% Confidence interval\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIPC guidance\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e4.668\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.238\u0026ndash;17.602\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidities\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e5.554\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.294\u0026ndash;23.843\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eIPC, infection prevention and control\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe three chemotherapy regimens most frequently used in breast cancer patients with axillary lymph node metastasis are AC-T (doxorubicin, cyclophosphamide, docetaxel), AT (doxorubicin, paclitaxel), and TAC. According to the National Comprehensive Cancer Network (NCCN) guidelines, all three regimens pose a high risk of neutropenia and its complications (\u0026gt;\u0026thinsp;20%).[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOur study focused on the TAC regimen, which was the most likely to show the prophylactic effect of IPC due to the high incidence of FN. Six-cycle TAC has the advantage of similar efficacy, but with a shorter treatment period, than eight-cycle AC followed by docetaxel.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] However, the TAC regimen has a very high rate of FN, with CIN occurring in 100% of patients receiving TAC chemotherapy and FN in 42.5\u0026ndash;63.4%.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] In our study, 97.6% patients developed CIN and 18.8% developed FN.\u003c/p\u003e \u003cp\u003eChemotherapy-induced FN is a severe adverse effect that can delay the chemotherapy schedule, reduce the relative dose intensity, and increase the hospitalization period, which increases costs.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] In addition, FN can cause life-threatening infections, with fatality rates of 5\u0026ndash;11%.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] The mortality rate of FN in our study was 12.5% (2/14), and there was no death in the IPC group. Risk factors for FN include age, performance status, gender, comorbidities, laboratory abnormalities, BMI, chemotherapy regimen, neutropenia prophylaxis, tumor type, disease progression, and genetic risk factors.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] In this study, these factors were controlled or analyzed, and only IPC and comorbidity were independently related to the development of FN.\u003c/p\u003e \u003cp\u003eThe use of prophylactic G-CSF improves the prognosis of patients on the TAC regimen by lowering the incidence and duration of FN.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] The NCCN, American Society of Clinical Oncology, and European Organization for the Research and Treatment of Cancer guidelines recommend routine use of primary G-CSF prophylaxis for high-risk cases (risk of FN\u0026thinsp;\u0026gt;\u0026thinsp;20%) based on several randomized controlled trials.[\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] The use of prophylactic ciprofloxacin can also lower the incidence of FN.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Despite these efforts, however, the rates of FN and its complications are still high.[\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] In addition, the side effects of these prophylactic drugs cannot be ignored. Ciprofloxacin can cause pancytopenia and G-CSF is associated with the development of acute myeloid leukemia.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] In comparison, mask wearing and physical distancing are free from the potential risks of various pharmaceutical preventive methods.\u003c/p\u003e \u003cp\u003eAll patients in this study had an ECOG score of 0, and received primary prophylactic pegfilgrastim to prevent FN and its complications, as well as prophylactic antibiotics when grade 4 NIC developed. The patients received all of these prophylactic drugs, and additional IPC significantly reduced the FN incidence rate, hospitalization duration, and hospital costs.\u003c/p\u003e \u003cp\u003eOne of the main causes of fever in CIN patients is respiratory infection, which has a high mortality rate. Most respiratory infections in FN are bacterial or fungal, which can be controlled to some extent with drugs. However, viruses are also a cause, and one study detected a virus in 41% of patients.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] After the COVID-19 outbreak, the World Health Organization and Centers for Disease Control promoted mask wearing and physical distancing. This prevention guidance has proven effective against the transmission of respiratory diseases.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] Our study showed that these guidelines were also effective in reducing the likelihood of FN in patients receiving TAC.\u003c/p\u003e \u003cp\u003eThere were limitations to this study. First, it was retrospective. However, it was conducted under conditions controlled by the state due to the pandemic, it should have higher reliability than other retrospective studies. Second, the number of patients was insufficient for a single-center study. However, the TAC regimen has a high incidence of FN and the preventive effect of IPC was better than expected; significant results were obtained despite the small study population.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIPC reduces the occurrence of FN and reduces hospitalization duration and costs. It should be performed during chemotherapy in all patients at high risk of developing FN.\u003c/p\u003e"},{"header":"Statements And Declarations","content":"\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Ye-Won Jeon], [Hongki Gwak] and [Young-Jin Suh]. The first draft of the manuscript was written by [HG] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Ye-Won Jeon], [Hongki Gwak] and [Young-Jin Suh]. The first draft of the manuscript was written by [HG] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by\u003c/em\u003e the institutional review board of the Catholic University of Korea (27-February-2022 / VC22RASI0019)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInstitutional Review Board waived the informed consent for this retrospective study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInstitutional Review Board waived the informed consent for this retrospective study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eRedig AJ, McAllister SS (2013) Breast cancer as a systemic disease: a view of metastasis J Intern Med 274: 113\u0026ndash;126, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/joim.12084\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eFontanella C, Bolzonello S, Lederer B, Aprile G (2014) Management of breast cancer patients with chemotherapy-induced neutropenia or febrile neutropenia Breast Care (Basel) 9: 239\u0026ndash;245, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1159/000366466\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCrawford J (2006) Risk assessment and guidelines for first-cycle colony-stimulating factor use in the management of chemotherapy-induced neutropenia Oncology (Williston Park) 20: 22-2822-28, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/pubmed/16736985\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMartin M, Lluch A, Segui MA, Ruiz A, Ramos M, Adrover E, Rodriguez-Lescure A, Grosse R, Calvo L, Fernandez-Chacon C, Roset M, Anton A, Isla D, del Prado PM, Iglesias L, Zaluski J, Arcusa A, Lopez-Vega JM, Munoz M, Mel JR (2006) Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen Ann Oncol 17: 1205\u0026ndash;1212, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1093/annonc/mdl135\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003evon Minckwitz G, Kummel S, du Bois A, Eiermann W, Eidtmann H, Gerber B, Hilfrich J, Huober J, Costa SD, Jackisch C, Grasshoff ST, Vescia S, Skacel T, Loibl S, Mehta KM, Kaufmann M, German Breast G (2008) Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. 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class=\"RefSource\"\u003ehttp://doi.org/10.6004/jnccn.2017.7038\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSmith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, Goldberg JM, Khatcheressian JL, Leighl NB, Perkins CL, Somlo G, Wade JL, Wozniak AJ, Armitage JO, American Society of Clinical O (2015) Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update J Clin Oncol 33: 3199\u0026ndash;3212, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1200/JCO.2015.62.3488\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSchnipper LE, Smith TJ, Raghavan D, Blayney DW, Ganz PA, Mulvey TM, Wollins DS (2012) American Society of Clinical Oncology identifies five key opportunities to improve care and reduce costs: the top five list for oncology J Clin Oncol 30: 1715\u0026ndash;1724, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1200/JCO.2012.42.8375\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C, European Organisation for R, Treatment of C (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours Eur J Cancer 47: 8\u0026ndash;32, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1016/j.ejca.2010.10.013\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eRabbi F, Qayum I, Humayun O, Khan MI, Khan UI, Abdullah HMA (2021) Ciprofloxacin-Associated Pancytopenia: A Rare Side Effect of a Commonly Prescribed Medication Am J Ther, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1097/MJT.0000000000001406\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHershman D, Neugut AI, Jacobson JS, Wang J, Tsai WY, McBride R, Bennett CL, Grann VR (2007) Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy J Natl Cancer Inst 99: 196\u0026ndash;205, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1093/jnci/djk028\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eEllis M (2008) Febrile neutropenia Ann N Y Acad Sci 1138: 329\u0026ndash;350, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1196/annals.1414.035\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHoward J, Huang A, Li Z, Tufekci Z, Zdimal V, van der Westhuizen HM, von Delft A, Price A, Fridman L, Tang LH, Tang V, Watson GL, Bax CE, Shaikh R, Questier F, Hernandez D, Chu LF, Ramirez CM, Rimoin AW (2021) An evidence review of face masks against COVID-19 Proc Natl Acad Sci U S A 118, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1073/pnas.2014564118\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSo JY, O\u0026apos;Hara NN, Kenaa B, Williams JG, deBorja CL, Slejko JF, Zafari Z, Sokolow M, Zimand P, Deming M, Marx J, Pollak AN, Reed RM (2021) Population Decline in COPD Admissions During the COVID-19 Pandemic Associated with Lower Burden of Community Respiratory Viral Infections Am J Med 134: 1252\u0026ndash;1259 e1253, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1016/j.amjmed.2021.05.008\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003cbr\u003e\u003cspan\u003eThe English in this document has been checked by at least two professional editors, both native speakers of English. For a certificate, please see:\u0026nbsp;\u003c/span\u003e\u003cspan\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.textcheck.com/certificate/IoPhn0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, infection prevention, febrile neutropenia, breast cancer","lastPublishedDoi":"10.21203/rs.3.rs-1588526/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1588526/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eChemotherapy-induced febrile neutropenia (FN) is a medical emergency that can cause severe adverse effects and death. Respiratory infection is one of the main causes of FN. We studied whether infection prevention and control (IPC) guidance for COVID-19 reduces the incidence of FN.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eWe reviewed female breast cancer patients treated with adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) with prophylactic pegfilgrastim between 2019 and 2021. IPC guidance has been implemented since April 2020.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThere was no difference in the incidence of chemotherapy-induced neutropenia (CIN) between patients without and with IPC. In the IPC patients, the incidence of FN (9.5%), hospitalization duration (0.7 ± 1.5 days), and total hospital cost (279.6 ± 42.6 USD) were significantly lower than in non-IPC patients (27.9%, 2.0 ± 3.8 days and 364.7 ± 271.6 USD, respectively).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eIPC guidance should be implemented to prevent FN in high-risk patients.\u003c/p\u003e","manuscriptTitle":"COVID-19 Prevention Guidance and the Incidence of Febrile Neutropenia in Breast Cancer Patients Receiving TAC Chemotherapy with Prophylactic Pegfilgrastim","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-27 16:47:02","doi":"10.21203/rs.3.rs-1588526/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a0b17e25-b741-493c-85b0-a8bd3177f0a8","owner":[],"postedDate":"April 27th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-10-06T07:44:16+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-27 16:47:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1588526","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1588526","identity":"rs-1588526","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}