Predictors of dropout from abemaciclib therapy in patients with breast cancer: a multicenter retrospective cohort study 

Predictors of dropout from abemaciclib therapy in patients with breast cancer: a multicenter retrospective cohort study | 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 Predictors of dropout from abemaciclib therapy in patients with breast cancer: a multicenter retrospective cohort study Noriaki Kataoka, Takeo Hata, Kouichi Hosomi, Atsushi Hirata, Ryosuke Ota, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4789012/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Oct, 2024 Read the published version in BMC Cancer → Version 1 posted 10 You are reading this latest preprint version Abstract Objective: This study explored the predictors of dropping out from abemaciclib therapy, a cyclin-dependent kinase 4 and 6 inhibitor, in patients with breast cancer. Material and Methods: Between November 2018 and March 2023, 147 patients with breast cancer treated with abemaciclib at Osaka Medical and Pharmaceutical University Hospital and Kindai University Nara Hospital were included. The exclusion criteria were as follows: lack of blood testing within 2 weeks prior to starting abemaciclib therapy, transfer to another facility after the commencement of abemaciclib therapy, and discontinuation of abemaciclib therapy due to the diagnosis of another cancer. The duration from the initiation of abemaciclib to dropout for any reason and to temporary suspension or dose reduction due to adverse events were analyzed as outcome variables using multivariate Cox regression analysis. Results: Baseline weight <54 kg, bone metastases, and hemoglobin level ≤12.4 g/dL were independent predictors of dropout for any reason. The main adverse events leading to dropout were liver enzyme elevation and gastrointestinal symptoms. Additionally, focusing on the adverse event of abemaciclib, a baseline weight <54 kg was an independent predictor of temporary suspension or dose reduction due to adverse events. The most common adverse events leading to temporary suspension or dose reduction were neutropenia and diarrhea. Conclusion: Patients with lower body weight are more susceptible to the adverse events of abemaciclib, increasing their risk of treatment dropout. In such patients, strict monitoring of adverse events and consideration of more frequent medical visits are necessary from the start of abemaciclib therapy. abemaciclib breast cancer chemotherapy dropout predictor Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Breast cancer is diagnosed at an early stage in over 90% of cases, with a mortality rate of approximately 15–20% relative to the incidence, indicating a higher survival rate compared to other cancers. 1 , 2 However, cases with breast cancer that recur are predominantly incurable, and patients achieving surgical remission are required to complete postoperative pharmacotherapy to suppress recurrence. 3 Moreover, even in cases of metastasis, pharmacotherapy can yield a five-year survival rate of approximately 25%, significantly affecting overall survival (OS). 4 Cyclin-dependent kinases (CDKs) 4 and 6 form complexes with cyclin D, inactivating the tumor suppressor retinoblastoma protein by phosphorylation, and facilitating cell cycle progression from G1 to S phase. 5 Abemaciclib is a novel anticancer agent that selectively inhibits the expression of CDK4 and 6. By selectively inhibiting these kinases, abemaciclib prevents the phosphorylation of retinoblastoma proteins, halting cell cycle progression from the G1 to S phase, and thereby suppressing tumor growth. 6 , 7 Over 50% of patients with breast cancer exhibit overexpression of cyclin D, 8 and excessive expression of cyclin D has been reported in estrogen receptor-positive cells. 9 Since 2014, international Phase III trials, specifically the MONARCH2 and MONARCH3 trials, have targeted hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative inoperable or recurrent breast cancer. The MONARCH2 trial demonstrated the efficacy and safety of abemaciclib in combination with fulvestrant, a selective estrogen receptor degrader, whereas the MONARCH3 trial demonstrated its effectiveness when combined with nonsteroidal aromatase inhibitors (NSAI), such as anastrozole or letrozole. 10 , 11 Consequently, in September 2018, abemaciclib was approved in Japan for the treatment of HR-positive and HER2-negative inoperable or recurrent breast cancers. Additionally, since 2017, an international Phase III monarchE trial has been conducted for adjuvant pharmacotherapy for HR-positive and HER2-negative breast cancer. The trial demonstrated that the combined administration of abemaciclib and adjuvant endocrine therapy significantly extended invasive disease-free survival (IDFS) compared to endocrine therapy alone in postoperative patients with HR-positive and HER2-negative breast cancer. Consequently, in December 2021, abemaciclib in combination with endocrine therapy was approved in Japan as an adjuvant pharmacotherapy for high-risk recurrent HR-positive and HER2-negative breast cancer. 12 Abemaciclib is the standard first-line therapy for inoperable or recurrent HR-positive, HER2-negative breast cancer. In the MONARCH2 trial, over 60% of patients treated with abemaciclib experienced Grade 3 or higher adverse events. Adverse events led to dropout from abemaciclib in 15.9% of patients and dose reduction in 42.9% of patients. 13 In the MONARCH3 study, 76.3% of patients experienced diarrhea, with 2.3% dropping out of abemaciclib therapy. 11 Additionally, 41.3% of patients developed neutropenia, which improved with temporary suspension of the therapy. In the monarchE study, 45.5% of patients experienced Grade 3 or higher adverse events, leading to dropout from abemaciclib in 16.6% of patients, with 4.8% of dropouts due to diarrhea. 12 These findings indicate a high incidence of Grade 3 or higher adverse events with abemaciclib. To extend the duration of abemaciclib treatment and significantly contribute to prolonged survival in patients with HR-positive and HER2-negative breast cancer, it is crucial to detect adverse events early and respond appropriately with timely interventions such as temporary suspension or dose reduction. Information on which patients are prone to temporary suspension or dose reduction, followed by dropout, and the adverse events associated with these outcomes, is therefore valuable. However, there is limited research on the predictors of dropout from abemaciclib therapy, and it is unclear which patient characteristics are associated with dropout. Therefore, this study aimed to investigate the predictors of dropout from abemaciclib therapy due to any reason. Materials and methods Patients Patients with breast cancer who received abemaciclib therapy at Osaka Medical and Pharmaceutical University Hospital and Kindai University Nara Hospital between November 2018 and March 2023 were included. Figure 1 demonstrates the study diagram. 14 The exclusion criteria were lack of blood testing within 2 weeks prior to starting abemaciclib therapy, transfer to another facility after treatment initiation, and discontinuation of abemaciclib therapy due to the diagnosis of another cancer. Measures The survey items included age, sex, height, weight, body mass index (BMI), HER2, estrogen receptor (ER), progesterone receptor (PgR), bone metastases, status, number of previous chemotherapy regimens, abemaciclib starting dose, hormonal agents used in combination, combination with luteinizing hormone-releasing hormone (LH-RH) agonists, combination with radiation, prescription of supportive medicine, and baseline levels of albumin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen, serum creatinine, white blood cell count, red blood cell count, hemoglobin, platelet count, and neutrophil count, all collected from electronic health records (EHR). Outcome The outcome variables included the duration from the initiation of abemaciclib therapy to dropout due to any reason, and the time to temporary suspension or dose reduction due to adverse events. The distinction between dropout due to any reason and temporary suspension or dose reduction due to adverse events was based on physician records and prescription history from the EHR. Statistical analysis Numerical variables were analyzed using the median as the cut-off value. Variables for the multivariate Cox regression analysis were selected using the stepwise method based on the Akaike Information Criterion (AIC), considering explanatory variables with a univariate Cox regression p -value <0.5. To account for multicollinearity, weight and BMI, as well as red blood cell count and hemoglobin, were not both included, and only the variable with the lower p -value was incorporated into the stepwise method. To verify the proportional hazards assumption of our Cox proportional hazards model, tests were conducted based on the Schoenfeld residuals. To assess multicollinearity among the predictors, the variance inflation factor (VIF) was calculated for each variable, with VIF values above 10 indicating significant multicollinearity. For sensitivity analysis, 10,000 bootstrap resampling iterations were performed to estimate the hazard ratio (HR). 15 In addition, the influence of individual observations on the HRs was assessed using the HRs obtained from subsets resampled using the jackknife method. 16 Next, we conduct a Cox regression analysis with elastic net regularization, which addresses variable selection and multicollinearity by combining the characteristics of ridge and lasso regressions. 17 To evaluate the impact of different regularization parameters, we performed a 10-fold cross-validation. We varied the mixing parameter α from 0 to 1 to balance regularization strength and variable selection, determining the optimal α value by minimizing the cross-validation error. Ridge regression occurs when α=0, and lasso regression occurs when α=1. Furthermore, we chose the regularization parameter λ that minimized the cross-validation error for model selection. The coefficients of the final model were estimated based on the selected α and λ. Through these analyses, we evaluated the robustness of the main results. All reported p -values were two-sided, with a significance level of p <0.05. Statistical analyses were performed using the R version 4.2.2 (R Development Core Team, Vienna, Austria). 18 This study adhered to the STROBE guidelines. 19 Results Study population Of the 147 patients who met the inclusion criteria, 137 patients were analyzed after excluding 7 patients who did not undergo blood tests within 2 weeks before starting abemaciclib therapy, 2 patients who were transferred after treatment initiation, and 1 patient in whom abemaciclib therapy was discontinued due to the diagnosis of another cancer (Figure S1). Background of the patients Table 1 presents patient characteristics. The median (interquartile range) age of the 137 patients was 61 years (50–72 years). Only patients who are HER2-negative (2+/FISH- or below) and HR-positive (ER or PgR positive) are eligible for abemaciclib therapy. Among the patients, 23 (17.4%), 65 (49.2%), 44 (33.3%), and five (3.6%) had HER2 2+/FISH-, HER2 1+, HER2 0, and an unknown HER2 status, respectively. Additionally, 124 (90.5%) patients were ER-positive, and 109 (79.6%) were PgR positive. There were 46 (33.6%) postoperative patients and 91 (66.4%) patients with recurrent disease progression, of whom 66 (48.2%) showed bone metastases. Hormone therapy is the first-line treatment for patients who are HR-positive. Of 137 patients, 86 (63.2%) had no history of chemotherapy. Among the 137 patients, 41 (29.9%) started treatment with a reduced initial dose, based on the physician's judgment. In addition, 28 patients (20.4%) underwent radiotherapy at some point after the initiation of abemaciclib therapy. Abemaciclib often causes a high incidence of diarrhea, and physicians may prescribe probiotics or antidiarrheals at the beginning of the treatment. In this study, probiotics were prescribed to 78 patients (56.9%), and 123 patients (89.8%) received loperamide or other antidiarrheals. Predictors of dropout from abemaciclib therapy Of the 137 patients, 71 dropped out of abemaciclib therapy during the follow-up period. Reasons for dropping out were adverse events and progressive disease (PD) in 36 (26.3%) and 35 (25.5%) patients, respectively. Adverse events leading to dropout from abemaciclib therapy were most frequently Grade 2 (21 patients, 58.3%) and Grade 3 (14 patients, 38.9%). The adverse events included increased liver enzymes in 7 patients (19.4%); gastrointestinal symptoms such as nausea, vomiting, and anorexia in 6 patients (16.7%); diarrhea, fatigue, and lung infection in 5 patients (13.9%); and others in 11 patients (30.6%). Some patients experienced multiple adverse events simultaneously, which led to their dropout from abemaciclib therapy (Table S1). Figure 2a shows the Kaplan-Meier curves for the duration of abemaciclib therapy dropout, with a median survival time (MST) of 386 days. Univariate Cox regression analysis revealed that patients with a baseline weight below 54 kg, a BMI below 22.06 kg/m 2 , bone metastases, postoperative status, and hemoglobin levels below 12.4 g/dL were significantly associated with a shorter duration of dropout from abemaciclib therapy. Multivariate Cox regression analysis using explanatory variables obtained through the stepwise method based on the univariate Cox regression results showed that a baseline weight <54 kg, bone metastases, and hemoglobin levels <12.4 g/dL were independent predictors of dropout from abemaciclib therapy (Table 2). Predictors of abemaciclib temporary suspension or dose reduction due to adverse events Among the 137 patients, 86 experienced temporary suspension or dose reduction because of adverse events during the follow-up period. The adverse events leading to temporary suspension or dose reduction of abemaciclib therapy were most frequent in Grades 3 (50 patients, 58.1%) and 2 (42 patients, 48.8%). The adverse events included neutropenia in 41 patients (47.7%), diarrhea in 30 patients (34.9%), increased liver enzymes in 5 patients (5.8%), fatigue in 4 patients (4.7%), and others in 18 patients (20.9%). Some patients experienced multiple adverse events simultaneously, which led to a temporary suspension or dose reduction (Table S2). Figure 2b shows the Kaplan-Meier curve for the duration of temporary suspension or dose reduction owing to adverse events, with an MST of 45 days. Univariate Cox regression analysis indicated that a baseline weight of <54 kg was significantly associated with a shorter duration of temporary suspension or dose reduction due to adverse events. Multivariate Cox regression analysis, using explanatory variables obtained through the stepwise method based on the univariate Cox regression results, showed that a baseline weight of <54 kg was an independent predictor of temporary suspension or dose reduction due to adverse events in abemaciclib therapy (Table 3). Sensitivity analysis In the multivariate Cox regression analysis shown in Table 2, which considered dropout from abemaciclib therapy as an outcome, the distribution of 10,000 HRs for each explanatory variable was estimated using the bootstrap method. The median HR and 95% confidence interval (CI) were 2.015 (1.226–3.433) for weight (<54 kg), 1.719 (1.018–2.953) for bone metastases, and 1.873 (1.119–3.352) for hemoglobin (≤12.4 g/dL) (Table S3 and Figure 3a). Next, using the jackknife method, we estimated the distribution of HRs for each explanatory variable and investigated the influence of each observation on the individual HRs. The influence of individual observations on the HRs for weight was greater than that of the other independent predictors (Table S4 and Figure 3b). Furthermore, we built a Cox regression model using elastic net regularization and through the optimized model, identified weight, bone metastasis, and hemoglobin level as significant predictors (Figures 3c and 3d, Tables S5 and S6). Similarly, for the multivariate Cox regression analysis shown in Table 3, where the outcome was temporary suspension or dose reduction of abemaciclib, the median HR and 95% CI obtained using the bootstrap method were 2.035 (1.332–3.165) for weights (<54 kg) (Table S7 and Figure 4a). Using the jackknife method, we estimated the distribution of the HRs for each explanatory variable and investigated the influence of individual observations on the HRs for weight (<54 kg). The influence of individual observations on the HRs for weight was smaller than that when dropout from abemaciclib therapy was considered the outcome (Table S8 and Figure 4b). Furthermore, the results from the Cox regression model using elastic net regularization identified weight as an important predictor. The sensitivity analyses were consistent with the main analysis and further supported the reliability of our conclusions (Figures 4c and 4d, Tables S9 and S10). Discussion This study, which focused on patients with breast cancer undergoing abemaciclib therapy, identified baseline weight below 54 kg, hemoglobin levels of 12.4 g/dL or less, and bone metastasis as predictors of dropout from abemaciclib therapy. Additionally, a baseline weight <54 kg was a predictor of temporary suspension or dose reduction due to adverse events. These findings were corroborated by multiple sensitivity analyses. According to a previous study on patients with HR-positive and HER2-negative inoperable or recurrent breast cancer treated with abemaciclib, the risk of Grade 3 or higher neutropenia is significantly lower in overweight or obese patients than in underweight or normal-weight patients. 20 This finding aligns with the results of the present study, which showed that low body weight was a predictor of dropout from abemaciclib therapy, temporary suspension, or dose reduction due to adverse events. In the jackknife method, the impact of individual weight observations on HR was smaller when temporary suspension or dose reduction was considered the outcome than when dropout was the outcome. Therefore, weight, which was detected as a significant predictor across both event types analyzed in this study, has a less pronounced dependency on individual observations when limited to adverse events. This suggests a strong correlation between weight and adverse events. Since the recommended dose of abemaciclib is standardized regardless of body weight or height, smaller patients may have higher blood concentrations of abemaciclib than patients with a standard build, potentially leading to a higher incidence and severity of certain adverse events. Reports suggest that lower baseline hemoglobin levels may reduce the tumor-shrinking effects of chemotherapy in patients with breast cancer. 21 This supports our finding that low hemoglobin levels are a predictor of dropout from abemaciclib therapy. According to a previous study, this mechanism involves the inhibition of antiproliferative activity due to reduced tumor oxygenation. In other words, lower hemoglobin levels make it more difficult for tumors to receive the oxygen required to inhibit growth. According to their hypothesis, low baseline hemoglobin levels may be predictors of treatment discontinuation in breast cancer beyond abemaciclib therapy. Baseline hemoglobin levels have also been reported as prognostic biomarkers for predicting clinical outcomes in many cancers. 22 This report demonstrated that patients with a low hemoglobin, albumin, lymphocyte, and platelet (HALP) score, calculated as [hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)]/platelets (/L), had a significantly shorter OS than those with high HALP scores. In this study, 36 of 137 patients with breast cancer who underwent abemaciclib therapy dropped out of the treatment owing to adverse events. The most common adverse events leading to dropout were increased liver enzymes in 7 patients (19.4%), gastrointestinal symptoms such as nausea, vomiting, and anorexia in 6 patients (16.7%), and diarrhea in 5 patients (13.9%). In the MONARCH2 trial, 70 of 441 patients (15.9%) discontinued treatment because of adverse events. 13 Among these, drug-induced liver injury was observed in 2 patients (2.9%), and ALT and AST elevations were observed in 1 patient each (1.4%), which was less frequent than in our study. 23 Approximately 30% of patients in the MONARCH2 trial were Asian, suggesting that Japanese patients might have a higher risk of treatment discontinuation due to increased liver enzymes. 13 Previous research has also reported that the Japanese subpopulation has a higher incidence of ALT and AST elevation after abemaciclib therapy than the global population. 23 Among the 137 patients who received abemaciclib therapy, 86 experienced temporary suspension or dose reduction due to adverse events during the follow-up period. Adverse events play a significant role in dropping out of abemaciclib therapy. Therefore, the present study investigated the predictors of adverse events leading to temporary suspension or dose reduction of abemaciclib therapy. These findings indicate that a low baseline body weight is a predictor. The most common adverse events that resulted in temporary suspension or dose reduction were neutropenia (41 patients, 47.7%), diarrhea (30 patients, 34.9%), and increased liver enzyme levels (5 patients, 5.8%). The MST for temporary suspension or dose reduction owing to adverse events was 45 days. Therefore, patients weighing less than 54 kg have a higher risk of adverse events, leading to temporary suspension or dose reduction. More stringent monitoring of adverse events and more frequent visits should be considered for at least the first 45 days of treatment. This study had several limitations. First, there are unmeasured confounding factors. Since this was a retrospective observational study, we could not adjust for confounding factors, such as smoking and drinking habits or medication adherence. Second, although this was a multicenter collaborative study, the sample size was relatively small. The eligible population for abemaciclib therapy was limited to patients with HR-positive and HER2-negative breast cancer; therefore, the number of users was low. As a result, the number of variables that could be analyzed in the multivariate analysis was limited. Third, this study only included Japanese patients. As mentioned previously, racial differences may influence the risk of adverse events. 23 As explored using the jackknife method, the influence of individual observations on the HR for weight gain when dropping out of abemaciclib therapy was relatively large. Analyzing populations with different demographic characteristics could result in different HRs. In the future, we believe that it will be necessary to conduct more detailed investigations considering the medical history, genetic mutations, and racial differences by accumulating more cases. In conclusion, low baseline body weight, bone metastasis, and low hemoglobin levels may serve as markers for dropping out of abemaciclib therapy. Additionally, a low baseline body weight may be a marker of adverse events that lead to temporary suspension or dose reduction of abemaciclib therapy. Therefore, patients with low body weight are more susceptible to adverse events during abemaciclib treatment, increasing their risk of dropping out and potentially limiting their ability to fully benefit from the therapy. Since more than half of these adverse events occur within the first 45 days of treatment, patients with low body weight should be closely monitored for adverse event for at least 45 days after starting abemaciclib. Previous studies have reported that the MONARCH2 and 3 trials demonstrated progression free survival with abemaciclib, regardless of dose reduction or the early onset of diarrhea and neutropenia. 24 Regular symptom assessments for patients receiving the CDK4/6 inhibitor palbociclib in combination with endocrine therapy have also been shown to improve quality of life. 25 Based on these findings, it is considered preferable to continue abemaciclib therapy, even with early dose reduction if adverse events are suspected, rather than risking dropout or prolonged treatment suspension due to worsening adverse events. Therefore, identifying patients at high risk for adverse events and increasing the frequency of adverse event monitoring and medical visits for these patients is crucial for the early detection and appropriate management of adverse events. However, these results alone do not recommend a temporary suspension or dose reduction to continue abemaciclib therapy. Further research is required to understand the effect of dose reduction on the efficacy of abemaciclib therapy in low-weight patients. Abbreviations OS Overall survival CDKs Cyclin-dependent kinases HR Hormone receptor HER2 Human epidermal growth factor receptor 2 NSAI Nonsteroidal aromatase inhibitors IDFS Invasive disease-free survival BMI Body mass index ER Estrogen receptor PgR Progesterone receptor LH-RH Luteinizing hormone-releasing hormone AST Aspartate aminotransferase ALT Alanine aminotransferase EHR Electronic health records AIC Akaike Information Criterion VIF Variance inflation factor HR Hazard ratio PD Progressive disease MST Median survival time CI Confidence interval HALP Hemoglobin albumin lymphocyte platelet Declarations Acknowledgements Not applicable. Funding No source of funding was used to conduct this study. Competing of interests The authors declare that they have no competing interests. Con sent of publication Not applicable. Ethical considerations This study was approved by the Ethics Committee of Osaka Medical and Pharmaceutical University (Approval ID:2023-127). As this was a retrospective observational study without intervention or invasion, using only existing electronic health record information, the requirement for patient consent was waived. Data availability statement The datasets generated and/or analysed during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request. Supplementary data Supplementary data is available on BMC Cancer online. References Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst 2014;106(5):dju055. Huang J, Chan PS, Lok V, et al. Global incidence and mortality of breast cancer: a trend analysis. Aging 2021;13(4):5748. Pedersen RN, Mellemkjær L, Ejlertsen B, et al. Mortality after late breast cancer recurrence in Denmark. J Clin Oncol 2022;40(13):1450. Sambi M, Qorri B, Harless W, Szewczuk MR. Therapeutic options for metastatic breast cancer. Adv Exp Med Biol 2019;1152:131. O'Leary B, Finn RS, Turner NC. Treating cancer with selective CDK4/6 inhibitors. Nat Rev Clin Oncol 2016;13(7):417. Gelbert LM, Cai S, Lin X, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Investig New Drugs 2014;32(5):825. Torres-Guzmán R, Calsina B, Hermoso A, et al. Preclinical characterization of abemaciclib in hormone receptor positive breast cancer. Oncotarget 2017;8(41):69493. Neuman E, Ladha MH, Lin N, et al. Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4. Mol Cell Biol 1997;17(9):5338. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012;490(7418):61. Sledge Jr GW, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: A randomized clinical trial. JAMA Oncol 2020;6(1):116. Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 2017;35(32):3638. Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol 2020;38(34):3987. Sledge Jr GW, Toi M, Neven P, et al. MONARCH2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 2017;35(25):2875. Schneeweiss S, Rassen JA, Brown JS, et al. Graphical depiction of longitudinal study designs in health care databases. Ann Intern Med 2019 ; 170(6):398. Efron B. 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Farag CM, Antar R, Akosman S, et al. What is hemoglobin, albumin, lymphocyte, platelet (HALP) score? A comprehensive literature review of HALP's prognostic ability in different cancer types. Oncotarget 2023;14:153. Inoue, K. et al. Japanese subpopulation analysis of MONARCH 2: phase 3 study of abemaciclib plus fulvestrant for treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that progressed on endocrine therapy. Breast Cancer 28 , 1038–1050 (2021). Rugo HS, Huober J, Garcia-Saenz JA, et al. Management of abmaciclib-associated adverse events in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: safety analysis of MONARCH 2 and MONARCH 3. The Oncologist 2021;26:e53-e65. Harbeck N, Fasching PA, Wuerstlein R, et al. Significantly longer time to deterioration of quality of life due to CANKADO PRO-React eHealth support in HRD HER2L metastatic breast cancer patients receiving palbociclib and endocrine therapy: primary outcome analysis of the multicenter randomized. Ann Oncol 2023 Aug;34(8):660-669. Tables Table 1. Clinical and demographic characteristics of patients. Characteristics Statistics Overall Patients n (%) 137 (100) Age (years) median (IQR) 61 (50–72) Sex Female n (%) 136 (99.3) Male n (%) 1 (0.7) Height (m) median (IQR) 1.56 (1.50–1.60) Weight (kg) median (IQR) 54 (49–60) Body mass index (kg/m 2 ) median (IQR) 22.1 (20.0–24.9) HER2 0 n (%) 44 (33.3) 1+ n (%) 65 (49.2) 2+ FISH- n (%) 23 (17.4) 2+ FISH+ n (%) 0 3+ n (%) 0 Unknown n (%) 5 (3.6) ER Positive n (%) 124 (90.5) Negative n (%) 1 (0.7) Unknown n (%) 12 (8.8) PgR Positive n (%) 109 (79.6) Negative n (%) 16 (11.7) Unknown n (%) 12 (8.8) Bone metastasis n (%) 66 (48.2) Status Postoperative n (%) 46 (33.6) Recurrent progression n (%) 91 (66.4) Number of previous chemotherapy regimens 0 n (%) 86 (63.2) 1 n (%) 27 (19.1) 2 n (%) 19 (14.0) 3 n (%) 4 (2.9) 4 n (%) 1 (0.7) Abemaciclib starting dose (mg) 300 n (%) 96 (70.1) 200 n (%) 35 (25.5) 100 n (%) 6 (4.4) Hormonal agents used in combination Antiestrogen (FUL, TAM) n (%) 72 (52.6) Aromatase inhibitor (LET, ANA) n (%) 65 (47.4) Combination with LH-RH agonists (LEU, GOS) n (%) 16 (11.7) Combination with radiation n (%) 28 (20.4) Prescription of supportive medicine Probiotics n (%) 78 (56.9) Antidiarrheal n (%) 123 (89.8) Clinical laboratory values Alanine aminotransferase (U/L) median (IQR) 16 (12–23) Albumin (g/dL) median (IQR) 4.1 (3.7–4.3) Aspartate aminotransferase (U/L) median (IQR) 23 (18–28) Blood urea nitrogen (mg/dL) median (IQR) 13 (11–16) Hemoglobin (g/dL) median (IQR) 12.4 (11.7–13.3) Neutrophil (/μL) median (IQR) 2,716 (1,953–4,432) Platelet (10 4 /μL) median (IQR) 220 (168–259) Red blood cell (10 3 /μL) median (IQR) 4,000 (3,725–4,340) Serum creatinine (mg/dL) median (IQR) 0.65 (0.56–0.76) Total bilirubin (mg/dL) median (IQR) 0.5 (0.4–0.6) White blood cell (/μL) median (IQR) 4,900 (3,755–6,340) ANA: anastrozole; ER: estrogen receptor; FUL: fulvestrant; GOS: goserelin; HER2: human epidermal growth factor receptor 2; IQR: interquartile range; LET: letrozole; LEU: leuprorelin; LH-RH: luteinizing hormone-releasing hormone; PgR: progesteron receptor; TAM: tamoxifen Table 2. Cox regression analysis for independent predictors of dropout from abemaciclib therapy due to any reason. Unadjusted Adjusted Variable Hazard ratio 95%CI p -value Hazard ratio 95%CI p -value VIF Age (≥61years) 1.273 0.798–2.031 0.311 Height (<1.56 m) 1.188 0.748–1.886 0.466 Weight (<54 kg) 2.021 1.262–3.238 0.003* 1.962 1.216–3.167 0.006* 1.027 Body mass index (<22.06 kg/m 2 ) 1.701 1.065–2.716 0.026* Bone metastasis 1.986 1.226–3.217 0.005* 1.708 1.048–2.784 0.032* 1.019 Status (Postoperative) 0.563 0.322–0.986 0.044* Number of previous chemotherapy regimens (≥1) 1.010 0.617–1.654 0.967 Starting dose down (<300 mg) 0.996 0.603–1.646 0.988 Hormonal agents used in combination (antiestrogen) 1.294 0.807–2.073 0.285 Combination with LH-RH agonists (LEU, GOS) 1.012 0.503–2.036 0.974 Combination with radiation 0.784 0.410–1.502 0.464 Prescription of supportive medicine Probiotics 1.294 0.808–2.072 0.284 Antidiarrheal 1.171 0.536–2.559 0.692 Clinical laboratory values Alanine aminotransferase (≥16 U/L) 1.069 0.667–1.713 0.782 Albumin (<4.1 g/dL) 1.198 0.750–1.915 0.449 Aspartate aminotransferase (≥23 U/L) 0.875 0.549–1.395 0.574 Blood urea nitrogen (≥13 mg/dL) 1.184 0.745–1.882 0.474 Hemoglobin (≤12.4 g/dL) 1.704 1.056–2.751 0.029* 1.848 1.129–3.024 0.028* 1.010 Neutrophil (<2,735 /μL) 0.911 0.573–1.447 0.692 Platelet (<220×10 4 /μL) 1.438 0.903–2.292 0.126 1.467 0.912–2.358 0.114 1.030 Red blood cell (<4,000✕10 3 /μL) 1.555 0.975–2.479 0.064 Serum creatinine (≥0.65 mg/dL) 1.163 0.727–1.858 0.529 Total bilirubin (≥0.5 mg/dL) 0.988 0.616–1.587 0.962 White blood cell (<4,900 /μL) 1.024 0.645–1.627 0.919 * p <0.05 CI: confidence interval; GOS: goserelin; LEU: leuprorelin; LH-RH: luteinizing hormone-releasing hormone; VIF: variance inflation factor Table 3. Cox regression analysis for independent predictors of abemaciclib temporary suspension or dose reduction due to adverse events. Unadjusted Adjusted Variable Hazard ratio 95%CI p -value Hazard ratio 95%CI p -value VIF Age (≥61 years) 0.929 0.612–1.410 0.730 Height (<1.56 m) 1.057 0.697–1.602 0.795 Weight (<54 kg) 1.941 1.271–2.963 0.002* 2.022 1.323–3.091 0.010* 1.022 Body mass index (<22.06 kg/m 2 ) 1.064 0.702–1.614 0.769 Bone metastasis 1.050 0.692–1.592 0.820 Status (Postoperative) 0.980 0.626–1.533 0.929 Number of previous chemotherapy regimens (≥1) 0.897 0.579–1.391 0.628 Starting dose down (<300 mg) 0.784 0.490–1.254 0.310 Hormonal agents used in combination (antiestrogen) 1.285 0.844–1.958 0.242 Combination with LH-RH agonists (LEU, GOS) 0.884 0.443–1.764 0.726 Combination with radiation 0.868 0.516–1.459 0.593 Prescription of supportive medicine Probiotics 1.154 0.755–1.762 0.508 Antidiarrheal 1.736 0.802–3.760 0.162 1.954 0.900–4.242 0.091 1.022 Clinical laboratory values Alanine aminotransferase (≥16 U/L) 1.151 0.758–1.750 0.509 Albumin (13 mg/dL) 0.875 0.577–1.327 0.530 Hemoglobin (<12.4 g/dL) 1.055 0.662–1.528 0.980 Neutrophil (<2,735 /μL) 0.996 0.657–1.510 0.985 Platelet (<220×10 4 /μL) 1.337 0.880–2.032 0.174 Red blood cell (<4,000×10 3 /μL) 1.410 0.929–2.140 0.107 Serum creatinine (≥0.65 mg/dL) 1.130 0.741–1.722 0.570 Total bilirubin (≥0.5 mg/dL) 1.356 0.878–2.092 0.169 White blood cell (<4,900 /μL) 0.977 0.644–1.481 0.911 * p <0.05 CI: confidence interval; GOS: goserelin; LEU: leuprorelin; LH-RH: luteinizing hormone-releasing hormone; VIF: variance inflation factor Additional Declarations No competing interests reported. Supplementary Files 20240723abemaciclibSupplementaryMaterialFigurever2.120240723.pptx 20240723abemaciclibSupplementaryMaterialTablever.2.520240723.docx Cite Share Download PDF Status: Published Journal Publication published 30 Oct, 2024 Read the published version in BMC Cancer → Version 1 posted Editorial decision: Revision requested 09 Sep, 2024 Reviews received at journal 09 Sep, 2024 Reviews received at journal 19 Aug, 2024 Reviewers agreed at journal 31 Jul, 2024 Reviewers agreed at journal 30 Jul, 2024 Reviewers invited by journal 29 Jul, 2024 Editor invited by journal 29 Jul, 2024 Editor assigned by journal 24 Jul, 2024 Submission checks completed at journal 24 Jul, 2024 First submitted to journal 23 Jul, 2024 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. 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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-4789012","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":342297157,"identity":"48a64096-2390-4099-be24-bc4afd261eb9","order_by":0,"name":"Noriaki Kataoka","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYJCCAwwHJBgkoEw5uDBjA0EtzGCmMVFaQCrhWhLxKgQBc/behwd+nLFgkGw/f/DDhzN26f1iZ49JMNTYMTDPxq7bsue4wcGeGxIM0jzJzJIzbiTnzpydlybBcCyZgXHOAaxaDG6kMRzg+SAB9HYyUNsH5twNt3PMJBjYDjAwzkjAqeXgH5AW/sfMv3k+1KcbgLX8w6/lMA/IYRLJbNI8Nw4ngLUwtuHRcuYYw2GZMxI8kjMem1nOOHPcEOiXZIvEvmQenH453sb88c2xOjmJ84mPb3w4Vi3PL5178MaHb3ZyhjhCDAZ4UNlAJ/EYzsCrA5t2eQnitYyCUTAKRsGwBgBkUmBuqC9mLAAAAABJRU5ErkJggg==","orcid":"","institution":"Osaka Medical and Pharmaceutical University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Noriaki","middleName":"","lastName":"Kataoka","suffix":""},{"id":342297158,"identity":"98ba7759-f666-41d5-aa83-8e39ff402421","order_by":1,"name":"Takeo Hata","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takeo","middleName":"","lastName":"Hata","suffix":""},{"id":342297159,"identity":"14c2a4ab-972b-436b-be06-d4200c032109","order_by":2,"name":"Kouichi Hosomi","email":"","orcid":"","institution":"Kindai University","correspondingAuthor":false,"prefix":"","firstName":"Kouichi","middleName":"","lastName":"Hosomi","suffix":""},{"id":342297160,"identity":"42382e8a-cb93-4745-b35a-daa324d43f3f","order_by":3,"name":"Atsushi Hirata","email":"","orcid":"","institution":"Kindai University Nara Hospital","correspondingAuthor":false,"prefix":"","firstName":"Atsushi","middleName":"","lastName":"Hirata","suffix":""},{"id":342297161,"identity":"f362734b-094f-495c-a6e1-2647d7d9713f","order_by":4,"name":"Ryosuke Ota","email":"","orcid":"","institution":"Kindai University Nara Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ryosuke","middleName":"","lastName":"Ota","suffix":""},{"id":342297162,"identity":"ae6f9a70-5bdc-40e4-8437-df07c3a062ee","order_by":5,"name":"Masami Nishihara","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Masami","middleName":"","lastName":"Nishihara","suffix":""},{"id":342297163,"identity":"5bd9a690-671e-4dcb-b66f-89a75d1d0b15","order_by":6,"name":"Kosei Kimura","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kosei","middleName":"","lastName":"Kimura","suffix":""},{"id":342297164,"identity":"daeaba29-3d70-40a5-a806-a10e8593dece","order_by":7,"name":"Mitsuhiko Iwamoto","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mitsuhiko","middleName":"","lastName":"Iwamoto","suffix":""},{"id":342297165,"identity":"b32b9d15-2c2e-4c6d-ae2d-e6aa9cc9926b","order_by":8,"name":"Akira Ashida","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Akira","middleName":"","lastName":"Ashida","suffix":""},{"id":342297166,"identity":"f9834e25-547e-4582-8fd0-450f4a4c15f4","order_by":9,"name":"Masashi Neo","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Masashi","middleName":"","lastName":"Neo","suffix":""}],"badges":[],"createdAt":"2024-07-23 13:14:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4789012/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4789012/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-024-13091-y","type":"published","date":"2024-10-30T16:12:55+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":63313035,"identity":"b089495b-325e-4ec8-b3e0-00a86cc43801","added_by":"auto","created_at":"2024-08-26 20:48:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":76365,"visible":true,"origin":"","legend":"\u003cp\u003eStudy diagram.\u003c/p\u003e\n\u003cp\u003eBMI, body mass index; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; LH-RH, luteinizing hormone-releasing hormone; PgR, progesterone receptor.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eEarliest outcome of interest: discontinuation of abemaciclib therapy, end of the study period.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4789012/v1/4e1a7f458ef1d8433f346c54.png"},{"id":63313033,"identity":"5661f78f-9cbe-4640-8341-2c3ead3588e7","added_by":"auto","created_at":"2024-08-26 20:48:04","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":48989,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curve for time to (a) dropout from abemaciclib therapy due to any reason and (b) abemaciclib temporary suspension or dose reduction due to adverse events.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4789012/v1/0bceb78f39271016ec4ab430.png"},{"id":63313468,"identity":"80ef78e3-cc18-4842-a87e-f1d100899519","added_by":"auto","created_at":"2024-08-26 20:56:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":104120,"visible":true,"origin":"","legend":"\u003cp\u003eSensitivity analysis for predictors of dropout from abemaciclib therapy due to any reason. (a) Density plot of hazard ratios from 10,000 bootstrap samples. (b) Influence plot for hazard ratios from subsets generated by jackknife resampling. Box plots show the median, third quartile, first quartile, and range of data points outside the quartile range, but excluding outliers. (c) Cross-validation error as a function of 𝜆. Error bars indicate the standard error of the cross-validation error at each 𝜆 value. The hyperparameter α, a measure of the mixture between ridge regression and lasso regression, was set to 0.9 based on the 10-fold cross-validation error. The vertical dashed red line corresponds to the value of regularization parameter λ that minimizes cross-validation error. (d) Regularization path for elastic net-regularized Cox regression.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4789012/v1/7b35cfbe8f8c2e22c356d58d.png"},{"id":63313037,"identity":"412ffd7f-926c-436a-ac15-2fd3b0e0d4a9","added_by":"auto","created_at":"2024-08-26 20:48:04","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":88915,"visible":true,"origin":"","legend":"\u003cp\u003eSensitivity analysis for predictors of abemaciclib temporary suspension or dose reduction due to adverse events. (a) Density plot of hazard ratios from 10,000 bootstrap samples. (b) Influence plot for hazard ratios from subsets generated by jackknife resampling. Box plots show the median, third quartile, first quartile, and range of data points outside the quartile range, but excluding outliers. (c) Cross-validation error as a function of 𝜆. Error bars indicate the standard error of the cross-validation error at each 𝜆 value. The hyperparameter α, a measure of the mixture between ridge regression and lasso regression, was set to 0.7 based on the 10-fold cross-validation error. The vertical dashed red line corresponds to the value of regularization parameter λ that minimizes cross-validation error. (d) Regularization path for elastic net-regularized Cox regression.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4789012/v1/639a51b40a4f64e1f7aa36f0.png"},{"id":68206407,"identity":"051df399-a5da-49ae-ba07-cde7e62c9fe5","added_by":"auto","created_at":"2024-11-04 16:32:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":959805,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4789012/v1/3e55ef74-7f15-4cd8-9300-5e97871a14dd.pdf"},{"id":63313467,"identity":"d1fe2864-2551-431f-be46-c89a5ce4ac6c","added_by":"auto","created_at":"2024-08-26 20:56:04","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":39364,"visible":true,"origin":"","legend":"","description":"","filename":"20240723abemaciclibSupplementaryMaterialFigurever2.120240723.pptx","url":"https://assets-eu.researchsquare.com/files/rs-4789012/v1/09dd78426c56d11d3533c733.pptx"},{"id":63313034,"identity":"fd9d3e2a-67f4-45b5-9c82-117729f87eba","added_by":"auto","created_at":"2024-08-26 20:48:04","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":45666,"visible":true,"origin":"","legend":"","description":"","filename":"20240723abemaciclibSupplementaryMaterialTablever.2.520240723.docx","url":"https://assets-eu.researchsquare.com/files/rs-4789012/v1/3780efba3e7c8ca933ab1f00.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictors of dropout from abemaciclib therapy in patients with breast cancer: a multicenter retrospective cohort study ","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer is diagnosed at an early stage in over 90% of cases, with a mortality rate of approximately 15–20% relative to the incidence, indicating a higher survival rate compared to other cancers.\u003csup\u003e1\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e2\u003c/sup\u003eHowever, cases with breast cancer that recur are predominantly incurable, and patients achieving surgical remission are required to complete postoperative pharmacotherapy to suppress recurrence.\u003csup\u003e3\u003c/sup\u003e Moreover, even in cases of metastasis, pharmacotherapy can yield a five-year survival rate of approximately 25%, significantly affecting overall survival (OS).\u003csup\u003e4\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCyclin-dependent kinases (CDKs) 4 and 6 form complexes with cyclin D, inactivating the tumor suppressor retinoblastoma protein by phosphorylation, and facilitating cell cycle progression from G1 to S phase.\u003csup\u003e5\u003c/sup\u003e Abemaciclib is a novel anticancer agent that selectively inhibits the expression of CDK4 and 6. By selectively inhibiting these kinases, abemaciclib prevents the phosphorylation of retinoblastoma proteins, halting cell cycle progression from the G1 to S phase, and thereby suppressing tumor growth.\u003csup\u003e6\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e7\u003c/sup\u003e Over 50% of patients with breast cancer exhibit overexpression of cyclin D,\u003csup\u003e8\u003c/sup\u003e and excessive expression of cyclin D has been reported in estrogen receptor-positive cells.\u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eSince 2014, international Phase III trials, specifically the MONARCH2 and MONARCH3 trials, have targeted hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative inoperable or recurrent breast cancer. The MONARCH2 trial demonstrated the efficacy and safety of abemaciclib in combination with fulvestrant,\u0026nbsp;a selective estrogen receptor degrader, whereas the MONARCH3 trial demonstrated its effectiveness when combined with nonsteroidal aromatase inhibitors (NSAI), such as anastrozole or letrozole.\u003csup\u003e10\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e11\u003c/sup\u003e Consequently, in September 2018, abemaciclib was approved in Japan for the treatment of HR-positive and HER2-negative inoperable or recurrent breast cancers.\u003c/p\u003e\n\u003cp\u003eAdditionally, since 2017, an international Phase III monarchE trial has been conducted for adjuvant pharmacotherapy for HR-positive and HER2-negative breast cancer. The trial demonstrated that the combined administration of abemaciclib and adjuvant endocrine therapy significantly extended invasive disease-free survival (IDFS) compared to endocrine therapy alone in postoperative patients with HR-positive and HER2-negative breast cancer. Consequently, in December 2021, abemaciclib in combination with endocrine therapy was approved in Japan as an adjuvant pharmacotherapy for high-risk recurrent HR-positive and HER2-negative breast cancer.\u003csup\u003e12\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eAbemaciclib is the standard first-line therapy for inoperable or recurrent HR-positive, HER2-negative breast cancer.\u0026nbsp;In the MONARCH2 trial, over 60% of patients treated with abemaciclib experienced Grade 3 or higher adverse events. Adverse events led to dropout from abemaciclib in 15.9% of patients and dose reduction in 42.9% of patients.\u003csup\u003e13\u003c/sup\u003e In the MONARCH3 study, 76.3% of patients experienced diarrhea, with 2.3% dropping out of abemaciclib therapy.\u003csup\u003e11\u003c/sup\u003e Additionally, 41.3% of patients developed neutropenia, which improved with temporary suspension of the therapy.\u0026nbsp;In the monarchE study, 45.5% of patients experienced Grade 3 or higher adverse events, leading to dropout from abemaciclib in 16.6% of patients, with 4.8% of dropouts due to diarrhea.\u003csup\u003e12\u003c/sup\u003e These findings indicate a high incidence of Grade 3 or higher adverse events with abemaciclib.\u003c/p\u003e\n\u003cp\u003eTo extend the duration of abemaciclib treatment and significantly contribute to prolonged survival in patients with HR-positive and HER2-negative breast cancer, it is crucial to detect adverse events early and respond appropriately with timely interventions such as temporary suspension or dose reduction. Information on which patients are prone to temporary suspension or dose reduction, followed by dropout, and the adverse events associated with these outcomes, is therefore valuable. However, there is limited research on the predictors of dropout from abemaciclib therapy, and it is unclear which patient characteristics are associated with dropout. Therefore, this study aimed to investigate the predictors of dropout from abemaciclib therapy due to any reason.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cem\u003ePatients\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePatients with breast cancer who received abemaciclib therapy at Osaka Medical and Pharmaceutical University Hospital and Kindai University Nara Hospital between November 2018 and March 2023 were included. Figure 1 demonstrates the study diagram.\u003csup\u003e14\u003c/sup\u003eThe exclusion criteria were lack of blood testing within 2 weeks prior to starting abemaciclib therapy, transfer to another facility after treatment initiation, and discontinuation of abemaciclib therapy due to the diagnosis of another cancer.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMeasures\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe survey items included age, sex, height, weight, body mass index (BMI), HER2, estrogen receptor (ER), progesterone receptor (PgR), bone metastases, status, number of previous chemotherapy regimens, abemaciclib starting dose, hormonal agents used in combination, combination with luteinizing hormone-releasing hormone (LH-RH) agonists, combination with radiation, prescription of supportive medicine, and baseline levels of albumin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen, serum creatinine, white blood cell count, red blood cell count, hemoglobin, platelet count, and neutrophil count, all collected from electronic health records (EHR).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOutcome\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe outcome variables included the duration from the initiation of abemaciclib therapy to dropout due to any reason, and the time to temporary suspension or dose reduction due to adverse events.\u0026nbsp;The distinction between dropout due to any reason and temporary suspension or dose reduction due to adverse events was based on physician records and prescription history from the EHR.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNumerical variables were analyzed using the median as the cut-off value. Variables for the multivariate Cox regression analysis were selected using the stepwise method based on the Akaike Information Criterion (AIC), considering explanatory variables with a univariate Cox regression \u003cem\u003ep\u003c/em\u003e-value \u0026lt;0.5.\u0026nbsp;To account for multicollinearity,\u0026nbsp;weight and BMI, as well as red blood cell count and hemoglobin, were not both included, and only the variable with the lower \u003cem\u003ep\u003c/em\u003e-value was incorporated into the stepwise method.\u0026nbsp;To verify the proportional hazards assumption of our Cox proportional hazards model, tests were conducted based on the Schoenfeld residuals. To assess multicollinearity among the predictors, the variance inflation factor (VIF) was calculated for each variable, with VIF values above 10 indicating significant multicollinearity.\u003c/p\u003e\n\u003cp\u003eFor sensitivity analysis, 10,000 bootstrap resampling iterations were performed to estimate the hazard ratio (HR).\u003csup\u003e15\u003c/sup\u003e In addition, the influence of individual observations on the HRs was assessed using the HRs obtained from subsets resampled using the jackknife method.\u003csup\u003e16\u003c/sup\u003e Next, we conduct a Cox regression analysis with elastic net regularization, which addresses variable selection and multicollinearity by combining the characteristics of ridge and lasso regressions.\u003csup\u003e17\u003c/sup\u003eTo evaluate the impact of different regularization parameters, we performed a 10-fold cross-validation.\u0026nbsp;We varied the mixing parameter α from 0 to 1 to balance regularization strength and variable selection, determining the optimal α value by minimizing the cross-validation error. Ridge regression occurs when α=0, and lasso regression occurs when α=1. Furthermore, we chose the regularization parameter λ that minimized the cross-validation error for model selection. The coefficients of the final model were estimated based on the selected α and λ. Through these analyses, we evaluated the robustness of the main results. All reported \u003cem\u003ep\u003c/em\u003e-values were two-sided, with a significance level of \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05. Statistical analyses were performed using the R version 4.2.2 (R Development Core Team, Vienna, Austria).\u003csup\u003e18\u003c/sup\u003e This study adhered to the STROBE guidelines.\u003csup\u003e19\u003c/sup\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eStudy population\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOf the 147 patients who met the inclusion criteria, 137 patients were analyzed after excluding 7 patients who did not undergo blood tests within 2 weeks before starting abemaciclib therapy, 2 patients who were transferred after treatment initiation, and 1 patient in whom abemaciclib therapy was discontinued due to the diagnosis of another cancer (Figure S1).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBackground of the patients\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 presents patient characteristics.\u0026nbsp;The median (interquartile range) age of the 137 patients was 61 years (50–72 years).\u0026nbsp;Only patients who are HER2-negative (2+/FISH- or below) and HR-positive (ER or PgR positive) are eligible for abemaciclib therapy.\u0026nbsp;Among the patients, 23 (17.4%), 65 (49.2%), 44 (33.3%), and five (3.6%) had HER2 2+/FISH-, HER2 1+, HER2 0, and an unknown HER2 status, respectively. Additionally, 124 (90.5%) patients were ER-positive, and 109 (79.6%) were PgR positive. There were 46 (33.6%) postoperative patients and 91 (66.4%) patients with recurrent disease progression, of whom 66 (48.2%) showed bone metastases. Hormone therapy is the first-line treatment for patients who are HR-positive. Of 137 patients, 86 (63.2%) had no history of chemotherapy. Among the 137 patients, 41 (29.9%) started treatment with a reduced initial dose, based on the physician's judgment. In addition, 28 patients (20.4%) underwent radiotherapy at some point after the initiation of abemaciclib therapy. Abemaciclib often causes a high incidence of diarrhea, and physicians may prescribe probiotics or antidiarrheals at the beginning of the treatment. In this study, probiotics were prescribed to 78 patients (56.9%), and 123 patients (89.8%) received loperamide or other antidiarrheals.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePredictors of dropout from abemaciclib therapy\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOf the 137 patients, 71 dropped out of abemaciclib therapy during the follow-up period. Reasons for dropping out were adverse events and progressive disease (PD) in 36 (26.3%) and 35 (25.5%) patients, respectively. Adverse events leading to dropout from abemaciclib therapy were most frequently Grade 2 (21 patients, 58.3%) and Grade 3 (14 patients, 38.9%). The adverse events included increased liver enzymes in 7 patients (19.4%); gastrointestinal symptoms such as nausea, vomiting, and anorexia in 6 patients (16.7%); diarrhea, fatigue, and lung infection in 5 patients (13.9%); and others in 11 patients (30.6%). Some patients experienced multiple adverse events simultaneously, which led to their dropout from abemaciclib therapy (Table S1). Figure 2a shows the Kaplan-Meier curves for the duration of abemaciclib therapy dropout, with a median survival time (MST) of 386 days. Univariate Cox regression analysis revealed that patients with a baseline weight below 54 kg, a BMI below 22.06 kg/m\u003csup\u003e2\u003c/sup\u003e, bone metastases, postoperative status, and hemoglobin levels below 12.4 g/dL were significantly associated with a shorter duration of dropout from abemaciclib therapy.\u0026nbsp;Multivariate Cox regression analysis using explanatory variables obtained through the stepwise method based on the univariate Cox regression results showed that a baseline weight \u0026lt;54 kg, bone metastases, and hemoglobin levels \u0026lt;12.4 g/dL were independent predictors of dropout from abemaciclib therapy (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePredictors of abemaciclib temporary suspension or dose reduction due to adverse events\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 137 patients, 86 experienced temporary suspension or dose reduction because of adverse events during the follow-up period. The adverse events leading to temporary suspension or dose reduction of abemaciclib therapy were most frequent in Grades 3 (50 patients, 58.1%) and 2 (42 patients, 48.8%). The adverse events included neutropenia in 41 patients (47.7%), diarrhea in 30 patients (34.9%), increased liver enzymes in 5 patients (5.8%), fatigue in 4 patients (4.7%), and others in 18 patients (20.9%). Some patients experienced multiple adverse events simultaneously, which led to a temporary suspension or dose reduction (Table S2). Figure 2b shows the Kaplan-Meier curve for the duration of temporary suspension or dose reduction owing to adverse events, with an MST of 45 days. Univariate Cox regression analysis indicated that a baseline weight of \u0026lt;54 kg was significantly associated with a shorter duration of temporary suspension or dose reduction due to adverse events.\u0026nbsp;Multivariate Cox regression analysis, using explanatory variables obtained through the stepwise method based on the univariate Cox regression results, showed that a baseline weight of \u0026lt;54 kg was an independent predictor of temporary suspension or dose reduction due to adverse events in abemaciclib therapy (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSensitivity analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn the multivariate Cox regression analysis shown in Table 2, which considered dropout from abemaciclib therapy as an outcome, the distribution of 10,000 HRs for each explanatory variable was estimated using the bootstrap method.\u0026nbsp;The median HR and 95% confidence interval (CI) were 2.015 (1.226–3.433) for weight (\u0026lt;54 kg), 1.719 (1.018–2.953) for bone metastases, and 1.873 (1.119–3.352) for hemoglobin (≤12.4 g/dL) (Table S3 and Figure 3a). Next, using the jackknife method, we estimated the distribution of HRs for each explanatory variable and investigated the influence of each observation on the individual HRs. The influence of individual observations on the HRs for weight was greater than that of the other independent predictors (Table S4 and Figure 3b). Furthermore, we built a Cox regression model using elastic net regularization and through the optimized model, identified weight, bone metastasis, and hemoglobin level as significant predictors (Figures 3c and 3d, Tables S5 and S6).\u003c/p\u003e\n\u003cp\u003eSimilarly, for the multivariate Cox regression analysis shown in Table 3, where the outcome was temporary suspension or dose reduction of abemaciclib, the median HR and 95% CI obtained using the bootstrap method were 2.035 (1.332–3.165) for weights (\u0026lt;54 kg) (Table S7 and Figure 4a). Using the jackknife method, we estimated the distribution of the HRs for each explanatory variable and investigated the influence of individual observations on the HRs for weight (\u0026lt;54 kg). The influence of individual observations on the HRs for weight was smaller than that when dropout from abemaciclib therapy was considered the outcome (Table S8 and Figure 4b). Furthermore, the results from the Cox regression model using elastic net regularization identified weight as an important predictor. The sensitivity analyses were consistent with the main analysis and further supported the reliability of our conclusions (Figures 4c and 4d, Tables S9 and S10).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study, which focused on patients with breast cancer undergoing abemaciclib therapy, identified baseline weight below 54 kg, hemoglobin levels of 12.4 g/dL or less, and bone metastasis as predictors of dropout from abemaciclib therapy.\u0026nbsp;Additionally, a baseline weight \u0026lt;54 kg was a predictor of temporary suspension or dose reduction due to adverse events. These findings were corroborated by multiple sensitivity analyses.\u003c/p\u003e\n\u003cp\u003eAccording to a previous study on patients with HR-positive and HER2-negative inoperable or recurrent breast cancer treated with abemaciclib, the risk of Grade 3 or higher neutropenia is significantly lower in overweight or obese patients than in underweight or normal-weight patients.\u003csup\u003e20\u003c/sup\u003e This finding aligns with the results of the present study, which showed that low body weight was a predictor of dropout from abemaciclib therapy, temporary suspension, or dose reduction due to adverse events.\u0026nbsp;In the jackknife method, the impact of individual weight observations on HR was smaller when temporary suspension or dose reduction was considered the outcome than when dropout was the outcome. Therefore, weight, which was detected as a significant predictor across both event types analyzed in this study, has a less pronounced dependency on individual observations when limited to adverse events. This suggests a strong correlation between weight and adverse events. Since the recommended dose of abemaciclib is standardized regardless of body weight or height, smaller patients may have higher blood concentrations of abemaciclib than patients with a standard build, potentially leading to a higher incidence and severity of certain adverse events.\u003c/p\u003e\n\u003cp\u003eReports suggest that lower baseline hemoglobin levels may reduce the tumor-shrinking effects of chemotherapy in patients with breast cancer.\u003csup\u003e21\u003c/sup\u003e This supports our finding that low hemoglobin levels are a predictor of dropout from abemaciclib therapy.\u0026nbsp;According to a previous study, this mechanism involves the inhibition of antiproliferative activity due to reduced tumor oxygenation. In other words, lower hemoglobin levels make it more difficult for tumors to receive the oxygen required to inhibit growth. According to their hypothesis, low baseline hemoglobin levels may be predictors of treatment discontinuation in breast cancer beyond abemaciclib therapy. Baseline hemoglobin levels have also been reported as prognostic biomarkers for predicting clinical outcomes in many cancers.\u003csup\u003e22\u003c/sup\u003e This report demonstrated that patients with a low\u0026nbsp;hemoglobin,\u0026nbsp;albumin,\u0026nbsp;lymphocyte,\u0026nbsp;and platelet\u0026nbsp;(HALP)\u0026nbsp;score, calculated as [hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)]/platelets (/L), had a significantly shorter OS than those with high HALP scores.\u003c/p\u003e\n\u003cp\u003eIn this study, 36 of 137 patients with breast cancer who underwent abemaciclib therapy dropped out of the treatment owing to adverse events.\u0026nbsp;The most common adverse events leading to dropout were increased liver enzymes in 7 patients (19.4%), gastrointestinal symptoms such as nausea, vomiting, and anorexia in 6 patients (16.7%), and diarrhea in 5 patients (13.9%). In the MONARCH2 trial, 70 of 441 patients (15.9%) discontinued treatment because of adverse events.\u003csup\u003e13\u003c/sup\u003e Among these, drug-induced liver injury was observed in 2 patients (2.9%), and ALT and AST elevations were observed in 1 patient each (1.4%), which was less frequent than in our study.\u003csup\u003e23\u003c/sup\u003e Approximately 30% of patients in the MONARCH2 trial were Asian, suggesting that Japanese patients might have a higher risk of treatment discontinuation due to increased liver enzymes.\u003csup\u003e13\u003c/sup\u003e Previous research has also reported that the Japanese subpopulation has a higher incidence of ALT and AST elevation after abemaciclib therapy than the global population.\u003csup\u003e23\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 137 patients who received abemaciclib therapy, 86 experienced temporary suspension or dose reduction due to adverse events during the follow-up period.\u0026nbsp;Adverse events play a significant role in dropping out of abemaciclib therapy. Therefore, the present study investigated the predictors of adverse events leading to temporary suspension or dose reduction of abemaciclib therapy. These findings indicate that a low baseline body weight is a predictor. The most common adverse events that resulted in temporary suspension or dose reduction were neutropenia (41 patients, 47.7%), diarrhea (30 patients, 34.9%), and increased liver enzyme levels (5 patients, 5.8%). The MST for temporary suspension or dose reduction owing to adverse events was 45 days. Therefore, patients weighing less than 54 kg have a higher risk of adverse events, leading to temporary suspension or dose reduction. More stringent monitoring of adverse events and more frequent visits should be considered for at least the first 45 days of treatment.\u003c/p\u003e\n\u003cp\u003eThis study had several limitations.\u0026nbsp;First, there are unmeasured confounding factors. Since this was a retrospective observational study, we could not adjust for confounding factors, such as smoking and drinking habits or medication adherence. Second, although this was a multicenter collaborative study, the sample size was relatively small. The eligible population for abemaciclib therapy was limited to patients with HR-positive and HER2-negative breast cancer; therefore, the number of users was low. As a result, the number of variables that could be analyzed in the multivariate analysis was limited. Third, this study only included Japanese patients. As mentioned previously, racial differences may influence the risk of adverse events.\u003csup\u003e23\u003c/sup\u003e As explored using the jackknife method, the influence of individual observations on the HR for weight gain when dropping out of abemaciclib therapy was relatively large. Analyzing populations with different demographic characteristics could result in different HRs. In the future, we believe that it will be necessary to conduct more detailed investigations considering the medical history, genetic mutations, and racial differences by accumulating more cases.\u003c/p\u003e\n\u003cp\u003eIn conclusion, low baseline body weight, bone metastasis, and low hemoglobin levels may serve as markers for dropping out of abemaciclib therapy.\u0026nbsp;Additionally, a low baseline body weight may be a marker of adverse events that lead to temporary suspension or dose reduction of abemaciclib therapy. Therefore, patients with low body weight are more susceptible to adverse events during abemaciclib treatment, increasing their risk of dropping out and potentially limiting their ability to fully benefit from the therapy. Since more than half of these adverse events occur within the first 45 days of treatment, patients with low body weight should be closely monitored for adverse event for at least 45 days after starting abemaciclib. Previous studies have reported that the MONARCH2 and 3 trials demonstrated progression free survival with abemaciclib, regardless of dose reduction or the early onset of diarrhea and neutropenia.\u003csup\u003e24\u003c/sup\u003eRegular symptom assessments for patients receiving the CDK4/6 inhibitor palbociclib in combination with endocrine therapy have also been shown to improve quality of life.\u003csup\u003e25\u003c/sup\u003e Based on these findings, it is considered preferable to continue abemaciclib therapy, even with early dose reduction if adverse events are suspected, rather than risking dropout or prolonged treatment suspension due to worsening adverse events. Therefore, identifying patients at high risk for adverse events and increasing the frequency of adverse event monitoring and medical visits for these patients is crucial for the early detection and appropriate management of adverse events.\u0026nbsp;However, these results alone do not recommend a temporary suspension or dose reduction to continue abemaciclib therapy.\u0026nbsp;Further research is required to understand the effect of dose reduction on the efficacy of abemaciclib therapy in low-weight patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eOS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Overall survival\u003c/p\u003e\n\u003cp\u003eCDKs \u0026nbsp;\u0026nbsp;Cyclin-dependent kinases\u003c/p\u003e\n\u003cp\u003eHR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Hormone receptor\u003c/p\u003e\n\u003cp\u003eHER2 \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Human epidermal growth factor receptor 2\u003c/p\u003e\n\u003cp\u003eNSAI \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Nonsteroidal aromatase inhibitors\u003c/p\u003e\n\u003cp\u003eIDFS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Invasive disease-free survival\u003c/p\u003e\n\u003cp\u003eBMI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Body mass index\u003c/p\u003e\n\u003cp\u003eER \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Estrogen receptor\u003c/p\u003e\n\u003cp\u003ePgR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Progesterone receptor\u003c/p\u003e\n\u003cp\u003eLH-RH \u0026nbsp; \u0026nbsp;\u0026nbsp;Luteinizing hormone-releasing hormone\u003c/p\u003e\n\u003cp\u003eAST \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Aspartate aminotransferase\u003c/p\u003e\n\u003cp\u003eALT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Alanine aminotransferase\u003c/p\u003e\n\u003cp\u003eEHR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Electronic health records\u003c/p\u003e\n\u003cp\u003eAIC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Akaike Information Criterion\u003c/p\u003e\n\u003cp\u003eVIF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Variance inflation factor\u003c/p\u003e\n\u003cp\u003eHR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Hazard ratio\u003c/p\u003e\n\u003cp\u003ePD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Progressive disease\u003c/p\u003e\n\u003cp\u003eMST \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Median survival time\u003c/p\u003e\n\u003cp\u003eCI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Confidence interval\u003c/p\u003e\n\u003cp\u003eHALP \u0026nbsp; \u0026nbsp; \u0026nbsp; Hemoglobin albumin lymphocyte platelet\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo source of funding was used to conduct this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no\u0026nbsp;competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCon\u003c/strong\u003e\u003cstrong\u003esent of publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Osaka Medical and Pharmaceutical University (Approval ID:2023-127). As this was a retrospective observational study without intervention or invasion, using only existing electronic health record information, the requirement for patient consent was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupplementary data is available on\u0026nbsp;\u003cem\u003eBMC Cancer\u003c/em\u003e online.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHowlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst\u003cem\u003e\u0026nbsp;\u003c/em\u003e2014;106(5):dju055.\u003c/li\u003e\n \u003cli\u003eHuang J, Chan PS, Lok V, et al. Global incidence and mortality of breast cancer: a trend analysis. Aging 2021;13(4):5748.\u003c/li\u003e\n \u003cli\u003ePedersen RN, Mellemkj\u0026aelig;r L, Ejlertsen B, et al. Mortality after late breast cancer recurrence in Denmark. J Clin Oncol 2022;40(13):1450.\u003c/li\u003e\n \u003cli\u003eSambi M, Qorri B, Harless W, Szewczuk MR. Therapeutic options for metastatic breast cancer. Adv Exp Med Biol 2019;1152:131.\u003c/li\u003e\n \u003cli\u003eO\u0026apos;Leary B, Finn RS, Turner NC. Treating cancer with selective CDK4/6 inhibitors. Nat Rev Clin Oncol 2016;13(7):417.\u003c/li\u003e\n \u003cli\u003eGelbert LM, Cai S, Lin X, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Investig New Drugs 2014;32(5):825.\u003c/li\u003e\n \u003cli\u003eTorres-Guzm\u0026aacute;n R, Calsina B, Hermoso A, et al. Preclinical characterization of abemaciclib in hormone receptor positive breast cancer. Oncotarget\u003cem\u003e\u0026nbsp;\u003c/em\u003e2017;8(41):69493.\u003c/li\u003e\n \u003cli\u003eNeuman E, Ladha MH, Lin N, et al. Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4. Mol Cell Biol 1997;17(9):5338.\u003c/li\u003e\n \u003cli\u003eCancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012;490(7418):61.\u003c/li\u003e\n \u003cli\u003eSledge Jr GW, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: A randomized clinical trial. JAMA Oncol 2020;6(1):116.\u003c/li\u003e\n \u003cli\u003eGoetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 2017;35(32):3638.\u003c/li\u003e\n \u003cli\u003eJohnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol 2020;38(34):3987.\u003c/li\u003e\n \u003cli\u003eSledge Jr GW, Toi M, Neven P, et al. MONARCH2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 2017;35(25):2875.\u003c/li\u003e\n \u003cli\u003eSchneeweiss S, Rassen JA, Brown JS, et al. Graphical depiction of longitudinal study designs in health care databases. Ann Intern Med 2019\u003cem\u003e;\u003c/em\u003e170(6):398.\u003c/li\u003e\n \u003cli\u003eEfron B. Bootstrap methods: another look at the jackknife. Ann Stat 1976;7(1):1.\u003c/li\u003e\n \u003cli\u003eMiller RG. The JackKnife a review. Biometrika 1974;61(1):1.\u003c/li\u003e\n \u003cli\u003eZou H, Hastie T. Regularization and variable selection via the elastic net. J R Statist Soc B. 2005;67:301-320.\u003c/li\u003e\n \u003cli\u003eR Development Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2024.\u003c/li\u003e\n \u003cli\u003evon Elm EV, Altman DG, Egger M, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 2007;335(7624):806.\u003c/li\u003e\n \u003cli\u003eFranzoi MA, Eiger D, Ameye L, et al. Clinical implications of body mass index in metastatic breast cancer patients treated with abemaciclib and endocrine therapy. J Natl Cancer Inst 2021;113(4):462.\u003c/li\u003e\n \u003cli\u003eBottini A, Berruti A, Brizzi MP, et al. Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer. Br J Cancer 2003;89(6):977.\u003c/li\u003e\n \u003cli\u003eFarag CM, Antar R, Akosman S, et al. What is hemoglobin, albumin, lymphocyte, platelet (HALP) score? A comprehensive literature review of HALP\u0026apos;s prognostic ability in different cancer types. Oncotarget 2023;14:153.\u003c/li\u003e\n \u003cli\u003eInoue, K. \u003cem\u003eet al.\u003c/em\u003e Japanese subpopulation analysis of MONARCH 2: phase 3 study of abemaciclib plus fulvestrant for treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that progressed on endocrine therapy. \u003cem\u003eBreast Cancer\u003c/em\u003e \u003cstrong\u003e28\u003c/strong\u003e, 1038\u0026ndash;1050 (2021).\u003c/li\u003e\n \u003cli\u003eRugo HS, Huober J, Garcia-Saenz JA, et al. Management of abmaciclib-associated adverse events in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: safety analysis of MONARCH 2 and MONARCH 3. The Oncologist 2021;26:e53-e65.\u003c/li\u003e\n \u003cli\u003eHarbeck N, Fasching PA, Wuerstlein R, et al. Significantly longer time to deterioration of quality of life due to CANKADO PRO-React eHealth support in HRD HER2L metastatic breast cancer patients receiving palbociclib and endocrine therapy: primary outcome analysis of the multicenter randomized. Ann Oncol 2023 Aug;34(8):660-669.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Clinical and demographic characteristics of patients.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"422\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003eStatistics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003ePatients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e137 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e61 (50\u0026ndash;72)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e136 (99.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eHeight (m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e1.56 (1.50\u0026ndash;1.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e54 (49\u0026ndash;60)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e22.1 (20.0\u0026ndash;24.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eHER2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e44 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e1+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e65 (49.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e2+ FISH-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e23 (17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e2+ FISH+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e3+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e5 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e124 (90.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e12 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003ePgR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e109 (79.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e16 (11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e12 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eBone metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e66 (48.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eStatus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003ePostoperative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e46 (33.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eRecurrent progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e91 (66.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eNumber of previous chemotherapy regimens\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e86 (63.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e27 (19.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e19 (14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e4 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eAbemaciclib starting dose (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e96 (70.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e35 (25.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e6 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eHormonal agents used in combination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eAntiestrogen (FUL, TAM)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e72 (52.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eAromatase inhibitor (LET, ANA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e65 (47.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eCombination with LH-RH agonists (LEU, GOS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e16 (11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eCombination with radiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e28 (20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003ePrescription of supportive medicine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eProbiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e78 (56.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eAntidiarrheal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e123 (89.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eClinical laboratory values\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eAlanine aminotransferase (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e16 (12\u0026ndash;23)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eAlbumin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e4.1 (3.7\u0026ndash;4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eAspartate aminotransferase (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e23 (18\u0026ndash;28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eBlood urea nitrogen (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e13 (11\u0026ndash;16)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e12.4 (11.7\u0026ndash;13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eNeutrophil (/\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e2,716 (1,953\u0026ndash;4,432)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003ePlatelet (10\u003csup\u003e4\u003c/sup\u003e/\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e220 (168\u0026ndash;259)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eRed blood cell (10\u003csup\u003e3\u003c/sup\u003e/\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e4,000 (3,725\u0026ndash;4,340)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eSerum creatinine (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e0.65 (0.56\u0026ndash;0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eTotal bilirubin (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e0.5 (0.4\u0026ndash;0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"56.39810426540284%\"\u003e\n \u003cp\u003eWhite blood cell (/\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.66824644549763%\"\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.933649289099527%\"\u003e\n \u003cp\u003e4,900 (3,755\u0026ndash;6,340)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"3\"\u003e\n \u003cp\u003eANA: anastrozole; \u0026nbsp;ER: estrogen receptor; FUL: fulvestrant; GOS: goserelin; HER2: human epidermal growth factor receptor 2; IQR: interquartile range; LET: letrozole; LEU: leuprorelin; LH-RH: luteinizing hormone-releasing hormone; PgR: progesteron receptor; TAM: tamoxifen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Table 2. Cox regression analysis for independent predictors of dropout from abemaciclib therapy due to any reason.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"28.29268292682927%\" colspan=\"3\"\u003e\n \u003cp\u003eUnadjusted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"36.58536585365854%\" colspan=\"4\"\u003e\n \u003cp\u003eAdjusted\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003eHazard ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003eHazard ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003eVIF\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eAge (\u0026ge;61years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.273\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.798\u0026ndash;2.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eHeight (\u0026lt;1.56 m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.188\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.748\u0026ndash;1.886\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.466\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eWeight (\u0026lt;54 kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e2.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e1.262\u0026ndash;3.238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.003*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\n \u003cp\u003e1.216\u0026ndash;3.167\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.006*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e1.027\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eBody mass index (\u0026lt;22.06 kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.701\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e1.065\u0026ndash;2.716\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.026*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eBone metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.986\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e1.226\u0026ndash;3.217\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.005*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.708\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\n \u003cp\u003e1.048\u0026ndash;2.784\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.032*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e1.019\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eStatus (Postoperative)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e0.563\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.322\u0026ndash;0.986\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.044*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eNumber of previous chemotherapy regimens (\u0026ge;1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.617\u0026ndash;1.654\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.967\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eStarting dose down (\u0026lt;300 mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.603\u0026ndash;1.646\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.988\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eHormonal agents used in combination (antiestrogen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.294\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.807\u0026ndash;2.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.285\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eCombination with LH-RH agonists (LEU, GOS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.503\u0026ndash;2.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.974\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eCombination with radiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e0.784\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.410\u0026ndash;1.502\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.464\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003ePrescription of supportive medicine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eProbiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.294\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.808\u0026ndash;2.072\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.284\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eAntidiarrheal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.536\u0026ndash;2.559\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.692\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eClinical laboratory values\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eAlanine aminotransferase (\u0026ge;16 U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.069\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.667\u0026ndash;1.713\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.782\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eAlbumin (\u0026lt;4.1 g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.198\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.750\u0026ndash;1.915\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eAspartate aminotransferase (\u0026ge;23 U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.549\u0026ndash;1.395\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eBlood urea nitrogen (\u0026ge;13 mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.184\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.745\u0026ndash;1.882\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.474\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eHemoglobin (\u0026le;12.4 g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.704\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e1.056\u0026ndash;2.751\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.029*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.848\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\n \u003cp\u003e1.129\u0026ndash;3.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.028*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e1.010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eNeutrophil (\u0026lt;2,735 /\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e0.911\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.573\u0026ndash;1.447\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.692\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003ePlatelet (\u0026lt;220\u0026times;10\u003csup\u003e4\u0026nbsp;\u003c/sup\u003e/\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.903\u0026ndash;2.292\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.467\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\n \u003cp\u003e0.912\u0026ndash;2.358\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e1.030\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eRed blood cell (\u0026lt;4,000✕10\u003csup\u003e3\u0026nbsp;\u003c/sup\u003e/\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.555\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.975\u0026ndash;2.479\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eSerum creatinine (\u0026ge;0.65 mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.727\u0026ndash;1.858\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.529\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eTotal bilirubin (\u0026ge;0.5 mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e0.988\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.616\u0026ndash;1.587\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.68292682926829%\"\u003e\n \u003cp\u003eWhite blood cell (\u0026lt;4,900 /\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e1.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.032520325203253%\"\u003e\n \u003cp\u003e0.645\u0026ndash;1.627\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.154471544715447%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.520325203252032%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.105691056910569%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.804878048780488%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"9\"\u003e\n \u003cp\u003e*\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"9\"\u003e\n \u003cp\u003eCI: confidence interval; GOS: goserelin; LEU: leuprorelin; LH-RH: luteinizing hormone-releasing hormone; VIF:\u0026nbsp;variance inflation factor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Table 3. Cox regression analysis for independent predictors of abemaciclib temporary suspension or dose reduction due to adverse events.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"607\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"28.61842105263158%\" colspan=\"3\"\u003e\n \u003cp\u003eUnadjusted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"37.00657894736842%\" colspan=\"4\"\u003e\n \u003cp\u003eAdjusted\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003eHazard ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003eHazard ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003eVIF\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eAge (\u0026ge;61 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e0.929\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.612\u0026ndash;1.410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.730\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eHeight (\u0026lt;1.56 m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.697\u0026ndash;1.602\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.795\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eWeight (\u0026lt;54 kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.941\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e1.271\u0026ndash;2.963\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e2.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\n \u003cp\u003e1.323\u0026ndash;3.091\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.010*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e1.022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eBody mass index (\u0026lt;22.06 kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.702\u0026ndash;1.614\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.769\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eBone metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.692\u0026ndash;1.592\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.820\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eStatus (Postoperative)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e0.980\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.626\u0026ndash;1.533\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.929\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eNumber of previous chemotherapy regimens (\u0026ge;1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e0.897\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.579\u0026ndash;1.391\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.628\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eStarting dose down (\u0026lt;300 mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e0.784\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.490\u0026ndash;1.254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.310\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eHormonal agents used in combination (antiestrogen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.285\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.844\u0026ndash;1.958\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eCombination with LH-RH agonists (LEU, GOS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e0.884\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.443\u0026ndash;1.764\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.726\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eCombination with radiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e0.868\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.516\u0026ndash;1.459\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.593\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003ePrescription of supportive medicine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eProbiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.755\u0026ndash;1.762\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eAntidiarrheal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.736\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.802\u0026ndash;3.760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.954\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\n \u003cp\u003e0.900\u0026ndash;4.242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e1.022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eClinical laboratory values\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eAlanine aminotransferase (\u0026ge;16 U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.151\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.758\u0026ndash;1.750\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.509\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eAlbumin (\u0026lt;4.1 g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.799\u0026ndash;1.842\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eAspartate aminotransferase (\u0026ge;23 U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.759\u0026ndash;1.754\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eBlood urea nitrogen (\u0026gt;13 mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.577\u0026ndash;1.327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.530\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eHemoglobin (\u0026lt;12.4 g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.662\u0026ndash;1.528\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.980\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eNeutrophil (\u0026lt;2,735 /\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.657\u0026ndash;1.510\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.985\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003ePlatelet (\u0026lt;220\u0026times;10\u003csup\u003e4\u0026nbsp;\u003c/sup\u003e/\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.337\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.880\u0026ndash;2.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eRed blood cell (\u0026lt;4,000\u0026times;10\u003csup\u003e3\u0026nbsp;\u003c/sup\u003e/\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.929\u0026ndash;2.140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eSerum creatinine (\u0026ge;0.65 mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.741\u0026ndash;1.722\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.570\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eTotal bilirubin (\u0026ge;0.5 mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e1.356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.878\u0026ndash;2.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.907894736842106%\"\u003e\n \u003cp\u003eWhite blood cell (\u0026lt;4,900 /\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\n \u003cp\u003e0.977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.171052631578947%\"\u003e\n \u003cp\u003e0.644\u0026ndash;1.481\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\n \u003cp\u003e0.911\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4671052631578947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.2368421052631575%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.664473684210526%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.210526315789474%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.894736842105263%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"9\"\u003e\n \u003cp\u003e*\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"9\"\u003e\n \u003cp\u003eCI: confidence interval; GOS: goserelin; LEU: leuprorelin; LH-RH: luteinizing hormone-releasing hormone; VIF:\u0026nbsp;variance inflation factor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"abemaciclib, breast cancer, chemotherapy, dropout, predictor","lastPublishedDoi":"10.21203/rs.3.rs-4789012/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4789012/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eObjective: \u003c/em\u003eThis study explored the predictors of dropping out from abemaciclib therapy, a cyclin-dependent kinase 4 and 6 inhibitor, in patients with breast cancer.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMaterial and Methods: \u003c/em\u003eBetween November 2018 and March 2023, 147 patients with breast cancer treated with abemaciclib at Osaka Medical and Pharmaceutical University Hospital and Kindai University Nara Hospital were included. The exclusion criteria were as follows: lack of blood testing within 2 weeks prior to starting abemaciclib therapy, transfer to another facility after the commencement of abemaciclib therapy, and discontinuation of abemaciclib therapy due to the diagnosis of another cancer. The duration from the initiation of abemaciclib to dropout for any reason and to temporary suspension or dose reduction due to adverse events were analyzed as outcome variables using multivariate Cox regression analysis.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eResults:\u003c/em\u003e Baseline weight \u0026lt;54 kg, bone metastases, and hemoglobin level ≤12.4 g/dL were independent predictors of dropout for any reason. The main adverse events leading to dropout were liver enzyme elevation and gastrointestinal symptoms. Additionally, focusing on the adverse event of abemaciclib, a baseline weight \u0026lt;54 kg was an independent predictor of temporary suspension or dose reduction due to adverse events. The most common adverse events leading to temporary suspension or dose reduction were neutropenia and diarrhea.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConclusion: \u003c/em\u003ePatients with lower body weight are more susceptible to the adverse events of abemaciclib, increasing their risk of treatment dropout. In such patients, strict monitoring of adverse events and consideration of more frequent medical visits are necessary from the start of abemaciclib therapy.\u003c/p\u003e","manuscriptTitle":"Predictors of dropout from abemaciclib therapy in patients with breast cancer: a multicenter retrospective cohort study ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 20:47:59","doi":"10.21203/rs.3.rs-4789012/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-09T14:23:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-09T13:57:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-19T18:23:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"79833736916291725049662605525055783499","date":"2024-07-31T14:09:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"131307485973242242027376717173203068757","date":"2024-07-30T14:22:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-29T13:55:39+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-29T06:20:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-25T03:04:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-25T03:04:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2024-07-23T13:12:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5cb328d4-2074-411c-8108-7175f19cd2b3","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-04T16:21:44+00:00","versionOfRecord":{"articleIdentity":"rs-4789012","link":"https://doi.org/10.1186/s12885-024-13091-y","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2024-10-30 16:12:55","publishedOnDateReadable":"October 30th, 2024"},"versionCreatedAt":"2024-08-26 20:47:59","video":"","vorDoi":"10.1186/s12885-024-13091-y","vorDoiUrl":"https://doi.org/10.1186/s12885-024-13091-y","workflowStages":[]},"version":"v1","identity":"rs-4789012","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4789012","identity":"rs-4789012","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}