Analysis of the Current Status of De Novo Stage IV Breast Cancer Surgery in China and the United States: A multicenter real-world study

Analysis of the Current Status of De Novo Stage IV Breast Cancer Surgery in China and the United States: A multicenter real-world 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 Analysis of the Current Status of De Novo Stage IV Breast Cancer Surgery in China and the United States: A multicenter real-world study Dongxu Ma, Heng Cao, Jiang Wu, Tongxuan Shang, Zizhao Guo, Lin Cong, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6598564/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background De novo stage IV breast cancer, characterized by distant metastases at diagnosis, poses significant treatment challenges. While systemic therapy remains the cornerstone of treatment, the role of surgical intervention for the primary tumor remains controversial. This study aimed to compare surgical treatment patterns and survival outcomes in de novo stage IV breast cancer patients between China and the United States using two large-scale national databases, to inform personalized treatment strategies and future guideline development. Methods This multicenter, retrospective cohort study included de novo stage IV breast cancer patients who underwent surgery from the National Cancer Center Oncology Information Database (NCCOID) and the Surveillance, Epidemiology, and End Results (SEER) database. The two cohorts were compared in clinical characteristics, treatment strategies, and survival outcomes. Kaplan-Meier analysis and multivariate Cox regression were used to identify factors associated with overall survival (OS). Results A total of 2,037 patients from China (2013–2020) and 3,175 from the US were included. Compared to SEER, the NCCOID cohort had a higher proportion of younger patients and more cases of T2-stage tumors. Mastectomy was the predominant surgical method in both countries, though breast-conserving surgery (BCS) was more common in the US. Chinese patients were more likely to receive preoperative systemic therapy. The NCCOID cohort showed superior OS (1-year: 91.5%, 3-year: 77.4%, 5-year: 67.9%) compared to SEER (1-year: 87.7%, 3-year: 62.8%, 5-year: 46.4%). Subgroup analyses revealed better survival in patients with HR + status, T-staging for smaller tumors, and bone-only metastases. Multivariate Cox regression confirmed that younger age (35–54), HR + status, HER2 + status, and limited metastases (especially bone-only metastases) were independently associated with improved OS. Conclusion Surgical treatment for de novo stage IV breast cancer is approached differently in China and the US, with variations in patient age, tumor characteristics, and systemic therapy timing. Selected patients—particularly those with HR + tumors, HER2 + tumors, smaller primary lesions, and limited metastases—may benefit from surgical resection. These findings support a personalized approach to surgery, emphasizing multidisciplinary decision-making. Prospective studies are needed to validate optimal surgical timing and patient selection. De novo stage IV breast cancer Primary tumor surgery Real-world study China and the United States Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Breast cancer remains the most prevalent malignancy among women worldwide, with significant implications for women’s health and quality of life [ 1 ]. Despite considerable advancements in screening technologies and early detection, which have led to higher rates of early-stage breast cancer diagnoses, a notable portion of patients are still identified at stage IV, where distant metastases are present at diagnosis [ 2 ]. Following significant improvements in early detection, the proportion of breast cancer cases diagnosed at a metastatic stage decreased from around 3.8–35.8% to 3.2–11.6%, varying among different areas between the early 2000s and 2015 onwards [ 3 ]. However, 0–6% in the US [ 4 ] and 3–10% in China [ 5 ] still present with stage IV disease. For patients with de novo stage IV breast cancer, where the cancer has metastasized at diagnosis, traditional guidelines typically emphasize systemic therapies, such as chemotherapy, targeted therapy, and endocrine therapy, over local surgical interventions [ 6 ]. Surgery for primary tumors in metastatic breast cancer patients has long been considered palliative, with no clear consensus on its survival benefits [ 7 , 8 ]. Recent breakthroughs in systemic therapies, including CDK4/6 inhibitors, PARP inhibitors, HER2-targeted antibody-drug conjugates (ADCs), and immunotherapy, have significantly extended survival in metastatic breast cancer of different molecular subtypes, potentially reshaping the paradigm of local intervention [ 9 – 13 ] However, emerging research has sparked renewed interest in the potential role of primary tumor resection for specific subgroups of de novo stage IV patients. Emerging data suggest cytoreductive surgery may enhance systemic therapy efficacy by reducing immunosuppressive tumor burden and eliminating resistant clones [ 14 ]. The MF07-01 trial demonstrated a 34% reduction in mortality risk with primary tumor resection in oligometastatic patients (HR 0.66, p = 0.005) [ 15 ], while EA2108 highlighted improved local control (16.3% vs. 39.8% progression, p < 0.001) [ 16 ]. Yet, large-scale real-world evidence to verify these potential benefits is limited, underscoring the need for comprehensive investigations. In clinical practice, several factors, such as genetic predispositions, healthcare resources, and treatment timing, also complicate the assessment of the role of surgery in de novo stage IV breast cancer [ 17 ]. Thus, this study analyzes a large dataset of de novo stage IV breast cancer patients from the US and China, two representative healthcare systems in the world, to compare demographic and healthcare differences. It focuses on surgical intervention trends, treatment evolution, and their impact on patient prognosis. The findings will help optimize surgical strategies and inform global clinical guidelines for managing de novo stage IV breast cancer. Method Data sources The data for the Chinese study were sourced from the National Cancer Center of China Tumor Information Database (NCCOID). These data were collected from the National Anti-Tumor Drug Surveillance System [ 18 ] and recorded by the National Cancer Registry System [ 19 , 20 ]. The database covers many cancer-related data, such as epidemiology, clinicopathology, and drug information. After strict quality control, information on the patient's baseline characteristics, clinical diagnoses, treatment regimens, and other relevant details was recorded in detail. The data for the US were obtained from the Surveillance, Epidemiology, and End Results (SEER) database [ 21 ], a program administered by the National Cancer Institute (NCI) that compiles cancer incidence, mortality, and other clinical data for selected states and counties across the US, representing approximately 35% of the US population. Study Design and Participants Patients included in the NCCOID and SEER databases were pathologically confirmed with stage IV breast cancer at diagnosis. All patients underwent surgical intervention, including mastectomy or breast-conserving surgery (BCS), with or without preoperative systemic therapy, postoperative chemoradiotherapy, and adjunctive treatments. The exclusion criteria were as follows: 1) diagnosis not confirmed by histology, 2) missing information on metastatic status or surgery data, 3) diagnosis based solely on autopsy or death certificate, 4) incomplete survival data, and 5) male patients. This study was approved by the Ethics Committee of the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College (23/026-3765). Data processing In this study, we analyzed key variables, including age and year of diagnosis, marital status, menopausal status, molecular subtypes, tumor (T) and lymph node (N) staging, metastatic sites at diagnosis, surgical and systemic treatments, and overall survival (OS). Missing data for certain statistical variables were addressed to minimize potential bias and enhance analytical accuracy. The Multiple Imputation by Chained Equations (MICE) method was applied to impute missing values [ 22 ]. Considering the nature of the data and variable correlations, each imputed dataset was analyzed independently, and the final results were derived by aggregating the analyses of all imputed datasets. To validate the plausibility of the imputed data, we compared distributions of key variables before and after imputation, assessing for significant differences. Additionally, the consistency of analytical outcomes across multiple imputed datasets was evaluated to ensure the stability of the imputation process and the reliability of the results. Statistical analysis Clinicopathologic characteristics and treatments in China and the US were compared using the chi-square test or Fisher's exact test. Kaplan-Meier analysis comparing survival outcomes between subgroups. Multivariate COX regression forest plots were used to visualize the effect size of the tested variables within each subgroup. Statistical analyses were performed using two-sided tests with a significance threshold set at p < 0.05. All statistical procedures were performed in R software (version 4.3.3). Result Clinicopathological Characteristics This study compared the characteristics of patients with de novo stage IV breast cancer among 2,516 patients from the NCCOID database and 3,175 patients from the SEER database, revealing significant differences in demographic, clinical, and treatment characteristics ( Table 1 ). In order to make a better comparison with the SEER database, we only included 2037 patients with the diagnosis year of 2013–2020 in the NCCOID database in the later comparison study. Compared with the SEER database, the NCCOID database had a higher proportion of younger patients (especially in the 35–54 year age group), whereas the SEER database had a higher proportion of older patients (especially in the 55–74 and ≥ 75 year age groups) (Fig. 1 A). In terms of T stage, NCCOID had the highest proportion of T2, whereas SEER had a relatively even proportion of T2-T4 (Fig. 1 B). N1 had the highest proportion in SEER, whereas NCCOID had a relatively balanced distribution of data but also had the highest proportion of N1 (Fig. 1 C). As for metastatic sites, more than 50% of patients with multiple metastatic sites in the NCCOID database, followed by patients with bone metastasis, while the proportion of patients with liver, lung, and brain metastasis was less than 10%; more than 50% of patients in SEER database had only bone metastasis, while brain metastasis was no more than 10%, and the distribution of liver, lung, and multiple metastatic sites was relatively balanced (Fig. 1 D). Molecular subtypes were defined based on the status of human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR), resulting in four subtypes: HR+/HER2+, HR+/HER2-, HR-/HER2+, and HR-/HER2-. The percentage of HR+/HER2- breast cancers in the NCCOID data has remained relatively stable over the years. The percentage of HR+/HER2 + breast cancers has gradually increased, and the HR-/HER2 + group fluctuated between 9.9% and 14.7% from 2013 to 2017 and then increased sharply to 21.8%, and the HR-/HER2- group decreased in proportion with each year. The percentage of each subtype in the SEER database remained relatively stable from year to year without significant fluctuations (Fig. 2 A-B). Surgical Treatment In terms of choice of surgical modality, mastectomy was much higher than BCS in both databases. In terms of choice of mastectomy, NCCOID was higher than SEER, with a share consistently higher than 80% and unchanged over the years (Fig. 3 A). In terms of timing of surgery, from 2013 to 2020, about 60% of patients in NCCOID will opt for preoperative systemic therapy, and interestingly less than 40% of patients in SEER will opt for preoperative systemic therapy, instead opting for surgery directly (Fig. 3 B). Overall Survival Analyses This study compared the 1-year, 3-year, and 5-year OS rates of breast cancer patients between the NCCOID database and the SEER database ( Table 2 ). The results showed that in the NCCOID cohort, the 1-year OS was 91.5%, the 3-year OS was 77.4%, and the 5-year OS was 67.9%. In contrast, the corresponding survival rates in the SEER cohort were 87.7%, 62.8%, and 46.4%, respectively. The comparison between the two groups revealed that the NCCOID cohort exhibited higher survival rates at all time points than the SEER cohort. Subgroup Analyses Further survival analyses were performed on 2,516 patients with stage IV breast cancer from the NCCOID database to understand which subgroups would have better survival after surgery. We performed a Kaplan-Meier survival analysis for different age groups (< 35 years, 35–54 years, 55–74 years, and ≥ 75 years), which showed that there was no statistically significant difference in 5-year OS between age subgroups (p = 0.055, Fig. 4 A). However, there was a trend for survival differences between different age groups, especially for patients in the ≥ 75 years age group, which showed a significant decrease in survival in the late follow-up period. There was a statistical difference in 5-year OS between age subgroups in the SEER database (p < 0.0001, Fig. 5 A). In NCCOID, there was no significant difference between mastectomy and BCS in terms of survival outcomes when looking at the choice of surgical modality (p = 0.54, Fig. 4 B), and the SEER database results showed a statistically significant difference between mastectomy and BCS in terms of 5-year OS. BCS has significantly better survival than mastectomy (p = 0.0011, Fig. 5 B). For the HR status, the results demonstrated a statistically significant discrepancy in 5-year OS between HR- and HR + patients, with superior survival outcomes observed in the HR + group (p = 0.045, Fig. 4 C). The SEER database yields the same conclusion (p < 0.0001, Fig. 5 C). In contrast, there was no statistical difference between HER2 + and HER2- patients in terms of 5-year OS (p = 0.52, Fig. 4 D). HER2 + patients in SEER had significantly better 5-year OS than HER2- patients (p < 0.0001, Fig. 5 D). There was a statistically significant difference in the T-stage (p < 0.0001, Fig. 4 E). The probability of survival decreased progressively with increasing T-stage. Patients with the T1 stage had the highest survival rate, and the curve was relatively smooth during the follow-up period, while patients with the T4 stage had the lowest survival rate. The SEER database was also statistically different regarding differences in OS across T-stages (p < 0.0001, Fig. 5 E). In terms of site of metastasis, the results showed that patients with simple bone metastasis had the best prognosis, followed by lung metastasis, followed by brain metastasis, followed by multisite metastasis, and liver metastasis was the worst, and there was a statistically significant difference (p < 0.0001, Fig. 4 F). The results of the SEER database showed that patients with bone metastases alone had the best prognosis and brain metastases the worst, and the difference was statistically significant (p < 0.0001, Fig. 5 F). Multivariate Analysis Multivariate Cox regression analysis was used to demonstrate the effect of each variable (e.g., age, menstrual status, treatment modality, tumor characteristics, etc.) on the OS (Fig. 6 ). It shows that age, tumor size, HER2 status, and metastatic site all have a significant impact on the survival of breast cancer patients. In contrast, age grouping of 35–54 (HR = 0.77, [95% CI: 0.63–0.94], p = 0.01) and HER2 + status (HR = 0.77, [95% CI: 0.65–0.91], p = 0.0019) were significantly associated with a lower risk of death. T2 group (HR = 1.3, [95% CI: 1-1.7], p = 0.033), T4 group (HR = 2, [95% CI: 1.5–2.6], p < 0.0001), brain metastases group (HR = 1.8, [95% CI: 1.3–2.6], p = 0.00094), hepatic metastases group (HR = 3.6, [95% CI: 1.7–7.3], p = 0.00051) and multisite metastases group (HR = 2.7, [95% CI: 2.3–3.2], p < 0.0001) were significantly associated with a higher risk of death. Discussion Compared with early-stage breast cancer, de novo stage IV breast cancer is inherently more aggressive and carries a poorer prognosis, making its management a significant clinical challenge. In addition, in recent years, there has been controversy over whether surgical intervention of the primary tumor should be performed for de novo stage IV breast cancer. This study provides information on the clinicopathologic of patients who underwent surgery for de novo stage IV breast cancer in China and the US. Our analysis revealed substantial differences in clinicopathologic characteristics and treatment patterns between the two cohorts. Compared with the SEER database, the NCCOID database recorded a higher proportion of younger patients, whereas the SEER database had a larger proportion of patients aged 55 years and older. In fact, Chinese women generally develop breast cancer at a younger age and are more willing to go for surgical treatment, whereas Western women tend to develop breast cancer after menopause [ 23 , 24 ], which is consistent with the epidemiological profile of breast cancer in Asian populations with a forward shift in the age of onset of the disease [ 25 ]. In the present study, the proportions of T-stages in the two cohorts also differed considerably, with a significantly higher proportion of T2-stage patients in NCCOID and a more prominent proportion of T4-stage patients in SEER. In some Chinese clinical practices, surgeons tend to prioritize early surgical control of the primary tumor in stage IV patients with T1-T2 disease and oligometastases, provided the patient’s systemic condition remains stable. This approach aims to mitigate the risk of local complications (e.g., rupture or infection) associated with tumor progression. As for the US, more emphasis is placed on systemic therapy as the mainstay of treatment, and for these patients, targeted, endocrine, or chemotherapy may be given first to observe the efficacy of the treatment and palliative surgery will be considered only when the T-stage is large and the local symptoms are obvious[ 26 , 27 ]. In this case, surgery may be used as a means of controlling local symptoms rather than prolonging survival [ 28 , 29 ]. In terms of the metastatic pattern, bone metastasis was the most common single type of metastasis in both groups of patients. Bone metastases are often associated with the HR + subtype, progress more slowly, and are capable of better survival outcomes [ 30 ]. Our study highlights a stark contrast in the adoption of surgical treatments between the two cohorts. While mastectomy remains the predominant surgical approach in both databases, the use of BCS is significantly higher in the US cohort. This could be attributed to the different treatment guidelines and patient preferences in each country, influenced by the availability of healthcare resources and the extent of public health education regarding breast cancer treatments. Although the majority of patients with de novo stage IV breast cancer undergo mastectomy, studies by Khan et al [ 31 ] and Kommalapati et al [ 32 ] have found that patients who undergo partial mastectomy with clear negative margins achieve the same OS rate and that both surgical procedures prolong patient survival compared with no surgery. A meta-analysis [ 33 ] that included 216,066 patients with new stage IV breast cancer similarly showed that both margin-negative BCS and mastectomy could be options for local management in such patients, but positive margins did not improve survival. Another study [ 34 ] showed that the 5-year OS rate was 13% in patients who did not undergo surgery on the primary site, 16% in patients who underwent surgery but had positive margins, and 27% in patients who underwent surgery with negative margins. Therefore, both BCS with negative margins and mastectomy can be used as optional surgical procedures for these patients. There were significant differences in the use of preoperative and postoperative systemic therapy between the two groups, suggesting a difference in the choice of timing of surgery between China and the US. A higher proportion of Chinese patients received preoperative systemic therapy, which may reflect a more aggressive treatment strategy in China, possibly due to a higher tumor load at diagnosis and the need to control systemic disease before local intervention. Patients who respond well to initial systemic therapy (chemotherapy, hormonal therapy, or targeted therapy) may be candidates for surgery [ 15 ]. Currently, there is no conclusive evidence on the timing of surgery for stage IV breast cancer. There are differences in the design and patient selection of several randomized controlled trials, with the TATA study [ 35 ], the EA2108 study [ 16 ] performing systemic therapy first and local surgery for patients who are sensitive to systemic therapy, and the MF07-01 study [ 15 ] adopting a more aggressive treatment strategy, with surgery followed by systemic therapy. Notably, a retrospective analysis in the United States [ 36 ] suggested that delayed surgery (> 3 months after diagnosis) may be associated with improved progression-free survival (PFS). A domestic study [ 37 ] further confirmed that primary resection reduces breast cancer-specific mortality regardless of the timing of surgery (before or after systemic therapy), and this benefit is particularly significant in a specific oligometastatic population (bone/lung/liver metastases and no brain metastases). Several retrospective studies [ 31 , 38 , 39 ] have shown that surgical treatment of primary tumors improves the prognosis of patients with de novo stage IV breast cancer, but the effects of patient heterogeneity and tumor subtype need to be taken into account, and the results of randomized clinical trials have not been consistently conclusive due to the rationalization of the development of systemic treatment regimens. Our subgroup analyses further demonstrated which types of patients benefit more from surgical treatment. For example, we found that younger patients benefited more, whereas older patients typically had lower survival rates, a result also reflected in the SEER data. In addition, ER + patients consistently showed better survival rates, possibly because ER + patients were able to receive endocrine therapy to slow or inhibit tumor growth, responded better to treatment, had a lower risk of disease progression, and therefore had a better prognosis [ 40 ]. This is the same conclusion obtained from previous studies. The subgroup analysis of the MF07-01 study showed that patients with HR+, HER2-, age < 55 years, and bone metastases only could benefit from localized therapy [ 15 ]. Hou et al. included 11974 patients with primary stage IV breast cancer from the SEER database and showed that HR+/HER2 + patients had the best prognosis, while HR -/HER2- patients had the worst prognosis [ 41 ]. A subgroup analysis of the JCOG1017 study demonstrated the same results, with improved overall survival for patients with ER-positive, premenopausal status, and single-organ metastases [ 42 ]. However, in a separate report on the outcomes of the TBCRC 013 trial by Prof. Tari A. King of the Dana-Farber Cancer Center, it was determined that the primary prognostic factor in patients with stage IV disease is the efficacy of first-line treatments. In addition, the impact of localized surgery may be relatively minor in patients who respond well to treatment. Thus, developing a surgical plan should be a collaborative process involving medical oncologists, surgeons, and the patients themselves [ 43 ]. Our findings support a tailored treatment strategy, in which surgical decisions are guided by individual patient profiles and tumor biology, rather than applying uniform management. This strategy could maximize the therapeutic benefits while minimizing unnecessary interventions. Limitation First, this study is a retrospective real-world analysis, and further prospective clinical studies are needed to establish whether surgery can offer improved survival benefits. Second, according to the corresponding datasets, the data sources and inclusion criteria differ between China and the US. Third, due to an inadequate cancer data registry system that leads to missing information, variables, and data with significant gaps are excluded. Conclusion In conclusion, the management of stage IV breast cancer requires careful consideration of multiple prognostic variables, including demographic factors, tumor biology, and treatment strategies. Our study provides a comprehensive comparison of how these elements interact within and between different healthcare systems, offering a direction for future research and policy-making to improve outcomes for this challenging patient population. Our findings suggest that select patients—particularly those with HR + disease, limited tumor burden, oligometastatic presentation, and favorable response to systemic therapy—may derive survival benefits from surgical intervention when R0 resection is achievable. Further studies are needed to refine the criteria for surgical candidacy in this group and to optimize systemic treatment protocols, aiming for the best possible quality of life and survival outcomes. Abbreviations ADCs antibody-drug conjugates BCS breast-conserving surgery HER2 human epidermal growth factor receptor 2 HR hormone receptor MICE Multiple Imputation by Chained Equations NCCOID National Cancer Center of China Tumor Information Database NCI National Cancer Institute OS overall survival PFS progression-free survival SEER Surveillance,Epidemiology,and End Results Declarations Funding This research was funded in part by the National Natural Science Foundation of China (Grant No. 82272938 to Jiaqi Liu), the Beijing Nova Program of Science and Technology (Grant No. 20220484059 to Jiaqi Liu), and the CAMS Innovation Fund for Medical Sciences (Grant No. 2021-I2M-1-014 to Jiaqi Liu and Xiang Wang). Author Contribution Dongxu Ma: Writing - original draft, Methodology, Formal analysis, Investigation, Data curation. Heng Cao: Writing - original draft, Formal analysis, Visualization. Jiang Wu: Writing - original draft, Data curation. Tongxuan Shang: Data curation. Zizhao Guo: Data curation. Lin Cong: Data curation. Ziqi Jia: Data curation. Yuchen Liu: Data curation. Jiaqi Liu: Writing–review & editing, Supervision, Conceptualization. Xiang Wang: Writing–review & editing, Supervision, Conceptualization. Data availability The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Ethical approval The study was approved by the Ethics Committees of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College (No. 23/026-3765). Conflicts of interest The authors declare no conflicts of interest. Acknowledgments None References Siegel, R.L., A.N. Giaquinto, and A. Jemal, Cancer statistics, 2024. CA Cancer J Clin, 2024. 74 (1): p. 12-49. Cardoso, F., et al., 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol, 2020. 31 (12): p. 1623-1649. 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Shien, T., et al., A randomized controlled trial comparing primary tumour resection plus systemic therapy with systemic therapy alone in metastatic breast cancer (PRIM-BC): Japan Clinical Oncology Group Study JCOG1017. Jpn J Clin Oncol, 2012. 42 (10): p. 970-3. King, T.A., et al., Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013. J Clin Oncol, 2016. 34 (20): p. 2359-65. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-6598564","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":456047194,"identity":"eb75b671-eedb-4ba8-9b0c-9842ef0a7f7c","order_by":0,"name":"Dongxu Ma","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Dongxu","middleName":"","lastName":"Ma","suffix":""},{"id":456047197,"identity":"a2e57aaf-edd8-419f-8a4e-29b45798c520","order_by":1,"name":"Heng Cao","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Heng","middleName":"","lastName":"Cao","suffix":""},{"id":456047198,"identity":"2de3225a-4aad-4f74-8dc6-0c9c38db09ff","order_by":2,"name":"Jiang Wu","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Jiang","middleName":"","lastName":"Wu","suffix":""},{"id":456047199,"identity":"adcde1bc-76c2-4c84-ba82-185bfa7bdde7","order_by":3,"name":"Tongxuan Shang","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Tongxuan","middleName":"","lastName":"Shang","suffix":""},{"id":456047200,"identity":"6105b14e-1ce6-4f02-8986-d8e278923b09","order_by":4,"name":"Zizhao Guo","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Zizhao","middleName":"","lastName":"Guo","suffix":""},{"id":456047201,"identity":"42ced173-fd93-4868-bbf6-894fe9de6150","order_by":5,"name":"Lin Cong","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Cong","suffix":""},{"id":456047202,"identity":"bd44584b-bfb6-4e91-8dce-247cfe745830","order_by":6,"name":"Ziqi Jia","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Ziqi","middleName":"","lastName":"Jia","suffix":""},{"id":456047203,"identity":"50c08ad8-8313-4213-beb8-0dd10547edfd","order_by":7,"name":"Yuchen Liu","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Yuchen","middleName":"","lastName":"Liu","suffix":""},{"id":456047204,"identity":"d9ea9f76-3817-4007-b553-c32c19e84b67","order_by":8,"name":"Jiaqi Liu","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Jiaqi","middleName":"","lastName":"Liu","suffix":""},{"id":456047205,"identity":"47e941c9-9013-45b3-84b8-f783bf17b8d6","order_by":9,"name":"Xiang Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYDACZjBpw8AGohJI0JJGihYIOEyCWoPjzM8efm07n9gn3cD84eEOOwb+9m78lkk2s5kby7bdTmyTOcAmkXgmmUHizNkNeLXwMzOYSUtuu23MJpHAxpDYxsxgIJGLXwsbM/s3oJZzIC3MHxLb6glr4WfmMZP8uO2AHFALg0Ri22HCWiSbecqkGf8ly7HJHGwDajnOQ9AvBuePb5P8ccaOR3528+GPP9uq5fjbe/FrAQFmHhApwdgAongIKgcBxh9gLUSpHQWjYBSMgpEIABVZPeRu/ctFAAAAAElFTkSuQmCC","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":true,"prefix":"","firstName":"Xiang","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-05-06 03:38:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6598564/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6598564/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82888633,"identity":"e1c1e609-65b5-466c-a7e9-38a72e38dd62","added_by":"auto","created_at":"2025-05-16 12:03:21","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":324816,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of different age groups, T-stages, N-stages, and metastatic sites between NCCOID and SEER databases\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Percentage of patients by age group (\u0026lt; 35, 35-54, 55-74, ≥ 75).\u003c/p\u003e\n\u003cp\u003e(B) Percentage of patients by T-stage (T1, T2, T3, T4).\u003c/p\u003e\n\u003cp\u003e(C) Percentage of patients by N-stage (N0, N1, N2, N3).\u003c/p\u003e\n\u003cp\u003e(D) Percentage of patients by metastatic sites (Hepatic metastasis, Pulmonary metastasis, Bone metastasis, Brain metastasis, Multisite metastasis).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6598564/v1/d2f625a0261340e54e67b9d3.jpeg"},{"id":82888634,"identity":"62c9ed44-a6a9-40d5-a536-a2201e166e7f","added_by":"auto","created_at":"2025-05-16 12:03:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":168966,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAnnual changes in different molecular typing at diagnosis in NCCOID and SEER from 2013 to 2020\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Percentage of different subtypes of breast cancer in NCCOID.\u003c/p\u003e\n\u003cp\u003e(B) Percentage of different subtypes of breast cancer in SEER.\u003c/p\u003e\n\u003cp\u003eHR, hormone receptor; HER2, human epidermal growth factor receptor 2\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6598564/v1/bd1068ead9f141cfe4a09b18.png"},{"id":82887051,"identity":"a5770c77-4c67-419f-9d51-c4c262c5d214","added_by":"auto","created_at":"2025-05-16 11:55:21","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":111852,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in annual rates of mastectomy and preoperative systemic therapy in NCCOID and SEER from 2013 to 2020.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Percentage change in choosing mastectomy.\u003c/p\u003e\n\u003cp\u003e(B) Percentage change in choosing preoperative systemic therapy\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6598564/v1/bbef1962430d531ccdd75ca8.png"},{"id":82887086,"identity":"09cfc77d-8ea2-42df-8ba9-b1edb72644c4","added_by":"auto","created_at":"2025-05-16 11:55:21","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":416450,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier survival curve comparing the overall survival rates of breast cancer patients in different age groups, surgical procedures, ER status, HER2 status, T-distribution and metastatic site over a 5-year follow-up period in NCCOID\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Comparison of 5-year overall survival in different age groups.\u003c/p\u003e\n\u003cp\u003e(B) Comparison of 5-year overall survival between BCS and mastectomy.\u003c/p\u003e\n\u003cp\u003e(C) Comparison of 5-year overall survival in ER status.\u003c/p\u003e\n\u003cp\u003e(D) Comparison of 5-year overall survival in HER2 status.\u003c/p\u003e\n\u003cp\u003e(E) Comparison of 5-year overall survival in different T-Stages.\u003c/p\u003e\n\u003cp\u003e(F) Comparison of 5-year overall survival in metastatic site.\u003c/p\u003e\n\u003cp\u003eBCS, breast-conserving surgery; MT, mastectomy; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6598564/v1/e010b001c87f079c33d3066a.png"},{"id":82887070,"identity":"491b4efd-607d-460e-83f1-8a73b58e755a","added_by":"auto","created_at":"2025-05-16 11:55:21","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":472854,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier survival curve comparing the overall survival rates of breast cancer patients in different age groups, surgical procedures, ER status, HER2 status, T-distribution and metastatic site over a 5-year follow-up period in SEER\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Comparison of 5-year overall survival in different age groups.\u003c/p\u003e\n\u003cp\u003e(B) Comparison of 5-year overall survival between BCS and mastectomy.\u003c/p\u003e\n\u003cp\u003e(C) Comparison of 5-year overall survival in ER status.\u003c/p\u003e\n\u003cp\u003e(D) Comparison of 5-year overall survival in HER2 status.\u003c/p\u003e\n\u003cp\u003e(E) Comparison of 5-year overall survival in different T-Stages.\u003c/p\u003e\n\u003cp\u003e(F) Comparison of 5-year overall survival in metastatic site.\u003c/p\u003e\n\u003cp\u003eBCS, breast-conserving surgery; MT, mastectomy; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6598564/v1/5ae34a53ada6cd54ac9386a6.png"},{"id":82887071,"identity":"397b87f8-4173-4f2e-83f8-c2ac51fb1508","added_by":"auto","created_at":"2025-05-16 11:55:21","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":74685,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plots for multivariate Cox regression analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eER, estrogen receptor; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; CI, confidence interval\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6598564/v1/29e6b66e29a6334132b12586.jpg"},{"id":83441003,"identity":"e2375dfa-7335-4534-a666-1b819633fc3b","added_by":"auto","created_at":"2025-05-26 09:33:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2308989,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6598564/v1/0538f705-ff67-46ea-b587-589409b031cc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of the Current Status of De Novo Stage IV Breast Cancer Surgery in China and the United States: A multicenter real-world study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer remains the most prevalent malignancy among women worldwide, with significant implications for women’s health and quality of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Despite considerable advancements in screening technologies and early detection, which have led to higher rates of early-stage breast cancer diagnoses, a notable portion of patients are still identified at stage IV, where distant metastases are present at diagnosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Following significant improvements in early detection, the proportion of breast cancer cases diagnosed at a metastatic stage decreased from around 3.8–35.8% to 3.2–11.6%, varying among different areas between the early 2000s and 2015 onwards [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, 0–6% in the US [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and 3–10% in China [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] still present with stage IV disease.\u003c/p\u003e \u003cp\u003eFor patients with \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer, where the cancer has metastasized at diagnosis, traditional guidelines typically emphasize systemic therapies, such as chemotherapy, targeted therapy, and endocrine therapy, over local surgical interventions [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Surgery for primary tumors in metastatic breast cancer patients has long been considered palliative, with no clear consensus on its survival benefits [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Recent breakthroughs in systemic therapies, including CDK4/6 inhibitors, PARP inhibitors, HER2-targeted antibody-drug conjugates (ADCs), and immunotherapy, have significantly extended survival in metastatic breast cancer of different molecular subtypes, potentially reshaping the paradigm of local intervention [\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e–\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] However, emerging research has sparked renewed interest in the potential role of primary tumor resection for specific subgroups of \u003cem\u003ede novo\u003c/em\u003e stage IV patients. Emerging data suggest cytoreductive surgery may enhance systemic therapy efficacy by reducing immunosuppressive tumor burden and eliminating resistant clones [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The MF07-01 trial demonstrated a 34% reduction in mortality risk with primary tumor resection in oligometastatic patients (HR 0.66, p = 0.005) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], while EA2108 highlighted improved local control (16.3% vs. 39.8% progression, p \u0026lt; 0.001) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Yet, large-scale real-world evidence to verify these potential benefits is limited, underscoring the need for comprehensive investigations.\u003c/p\u003e \u003cp\u003eIn clinical practice, several factors, such as genetic predispositions, healthcare resources, and treatment timing, also complicate the assessment of the role of surgery in \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Thus, this study analyzes a large dataset of \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer patients from the US and China, two representative healthcare systems in the world, to compare demographic and healthcare differences. It focuses on surgical intervention trends, treatment evolution, and their impact on patient prognosis. The findings will help optimize surgical strategies and inform global clinical guidelines for managing \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eData sources\u003c/p\u003e\u003cp\u003eThe data for the Chinese study were sourced from the National Cancer Center of China Tumor Information Database (NCCOID). These data were collected from the National Anti-Tumor Drug Surveillance System [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and recorded by the National Cancer Registry System [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The database covers many cancer-related data, such as epidemiology, clinicopathology, and drug information. After strict quality control, information on the patient's baseline characteristics, clinical diagnoses, treatment regimens, and other relevant details was recorded in detail. The data for the US were obtained from the Surveillance, Epidemiology, and End Results (SEER) database [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], a program administered by the National Cancer Institute (NCI) that compiles cancer incidence, mortality, and other clinical data for selected states and counties across the US, representing approximately 35% of the US population.\u003c/p\u003e\u003cp\u003eStudy Design and Participants\u003c/p\u003e\u003cp\u003ePatients included in the NCCOID and SEER databases were pathologically confirmed with stage IV breast cancer at diagnosis. All patients underwent surgical intervention, including mastectomy or breast-conserving surgery (BCS), with or without preoperative systemic therapy, postoperative chemoradiotherapy, and adjunctive treatments. The exclusion criteria were as follows: 1) diagnosis not confirmed by histology, 2) missing information on metastatic status or surgery data, 3) diagnosis based solely on autopsy or death certificate, 4) incomplete survival data, and 5) male patients.\u003c/p\u003e\u003cp\u003e This study was approved by the Ethics Committee of the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College (23/026-3765).\u003c/p\u003e\u003cp\u003eData processing\u003c/p\u003e\u003cp\u003eIn this study, we analyzed key variables, including age and year of diagnosis, marital status, menopausal status, molecular subtypes, tumor (T) and lymph node (N) staging, metastatic sites at diagnosis, surgical and systemic treatments, and overall survival (OS). Missing data for certain statistical variables were addressed to minimize potential bias and enhance analytical accuracy. The Multiple Imputation by Chained Equations (MICE) method was applied to impute missing values [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Considering the nature of the data and variable correlations, each imputed dataset was analyzed independently, and the final results were derived by aggregating the analyses of all imputed datasets. To validate the plausibility of the imputed data, we compared distributions of key variables before and after imputation, assessing for significant differences. Additionally, the consistency of analytical outcomes across multiple imputed datasets was evaluated to ensure the stability of the imputation process and the reliability of the results.\u003c/p\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eClinicopathologic characteristics and treatments in China and the US were compared using the chi-square test or Fisher's exact test. Kaplan-Meier analysis comparing survival outcomes between subgroups. Multivariate COX regression forest plots were used to visualize the effect size of the tested variables within each subgroup. Statistical analyses were performed using two-sided tests with a significance threshold set at p \u0026lt; 0.05. All statistical procedures were performed in R software (version 4.3.3).\u003c/p\u003e"},{"header":"Result","content":"\u003ch2\u003eClinicopathological Characteristics\u003c/h2\u003e\u003cp\u003eThis study compared the characteristics of patients with \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer among 2,516 patients from the NCCOID database and 3,175 patients from the SEER database, revealing significant differences in demographic, clinical, and treatment characteristics (\u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e).\u003c/p\u003e\u003cp\u003eIn order to make a better comparison with the SEER database, we only included 2037 patients with the diagnosis year of 2013–2020 in the NCCOID database in the later comparison study. Compared with the SEER database, the NCCOID database had a higher proportion of younger patients (especially in the 35–54 year age group), whereas the SEER database had a higher proportion of older patients (especially in the 55–74 and ≥ 75 year age groups) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). In terms of T stage, NCCOID had the highest proportion of T2, whereas SEER had a relatively even proportion of T2-T4 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). N1 had the highest proportion in SEER, whereas NCCOID had a relatively balanced distribution of data but also had the highest proportion of N1 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC).\u003c/p\u003e\u003cp\u003eAs for metastatic sites, more than 50% of patients with multiple metastatic sites in the NCCOID database, followed by patients with bone metastasis, while the proportion of patients with liver, lung, and brain metastasis was less than 10%; more than 50% of patients in SEER database had only bone metastasis, while brain metastasis was no more than 10%, and the distribution of liver, lung, and multiple metastatic sites was relatively balanced (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD).\u003c/p\u003e\u003cp\u003eMolecular subtypes were defined based on the status of human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR), resulting in four subtypes: HR+/HER2+, HR+/HER2-, HR-/HER2+, and HR-/HER2-. The percentage of HR+/HER2- breast cancers in the NCCOID data has remained relatively stable over the years. The percentage of HR+/HER2 + breast cancers has gradually increased, and the HR-/HER2 + group fluctuated between 9.9% and 14.7% from 2013 to 2017 and then increased sharply to 21.8%, and the HR-/HER2- group decreased in proportion with each year. The percentage of each subtype in the SEER database remained relatively stable from year to year without significant fluctuations (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-B).\u003c/p\u003e\u003ch3\u003eSurgical Treatment\u003c/h3\u003e\u003cp\u003eIn terms of choice of surgical modality, mastectomy was much higher than BCS in both databases. In terms of choice of mastectomy, NCCOID was higher than SEER, with a share consistently higher than 80% and unchanged over the years (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). In terms of timing of surgery, from 2013 to 2020, about 60% of patients in NCCOID will opt for preoperative systemic therapy, and interestingly less than 40% of patients in SEER will opt for preoperative systemic therapy, instead opting for surgery directly (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e\u003ch3\u003eOverall Survival Analyses\u003c/h3\u003e\u003cp\u003eThis study compared the 1-year, 3-year, and 5-year OS rates of breast cancer patients between the NCCOID database and the SEER database (\u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e). The results showed that in the NCCOID cohort, the 1-year OS was 91.5%, the 3-year OS was 77.4%, and the 5-year OS was 67.9%. In contrast, the corresponding survival rates in the SEER cohort were 87.7%, 62.8%, and 46.4%, respectively. The comparison between the two groups revealed that the NCCOID cohort exhibited higher survival rates at all time points than the SEER cohort.\u003c/p\u003e\u003ch3\u003eSubgroup Analyses\u003c/h3\u003e\u003cp\u003eFurther survival analyses were performed on 2,516 patients with stage IV breast cancer from the NCCOID database to understand which subgroups would have better survival after surgery. We performed a Kaplan-Meier survival analysis for different age groups (\u0026lt; 35 years, 35–54 years, 55–74 years, and ≥ 75 years), which showed that there was no statistically significant difference in 5-year OS between age subgroups (p = 0.055, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). However, there was a trend for survival differences between different age groups, especially for patients in the ≥ 75 years age group, which showed a significant decrease in survival in the late follow-up period.\u003c/p\u003e\u003cp\u003eThere was a statistical difference in 5-year OS between age subgroups in the SEER database (p \u0026lt; 0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). In NCCOID, there was no significant difference between mastectomy and BCS in terms of survival outcomes when looking at the choice of surgical modality (p = 0.54, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB), and the SEER database results showed a statistically significant difference between mastectomy and BCS in terms of 5-year OS. BCS has significantly better survival than mastectomy (p = 0.0011, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB).\u003c/p\u003e\u003cp\u003eFor the HR status, the results demonstrated a statistically significant discrepancy in 5-year OS between HR- and HR + patients, with superior survival outcomes observed in the HR + group (p = 0.045, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC). The SEER database yields the same conclusion (p \u0026lt; 0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC). In contrast, there was no statistical difference between HER2 + and HER2- patients in terms of 5-year OS (p = 0.52, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD). HER2 + patients in SEER had significantly better 5-year OS than HER2- patients (p \u0026lt; 0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eD).\u003c/p\u003e\u003cp\u003eThere was a statistically significant difference in the T-stage (p \u0026lt; 0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eE). The probability of survival decreased progressively with increasing T-stage. Patients with the T1 stage had the highest survival rate, and the curve was relatively smooth during the follow-up period, while patients with the T4 stage had the lowest survival rate. The SEER database was also statistically different regarding differences in OS across T-stages (p \u0026lt; 0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eE).\u003c/p\u003e\u003cp\u003eIn terms of site of metastasis, the results showed that patients with simple bone metastasis had the best prognosis, followed by lung metastasis, followed by brain metastasis, followed by multisite metastasis, and liver metastasis was the worst, and there was a statistically significant difference (p \u0026lt; 0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eF). The results of the SEER database showed that patients with bone metastases alone had the best prognosis and brain metastases the worst, and the difference was statistically significant (p \u0026lt; 0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eF).\u003c/p\u003e\u003ch3\u003eMultivariate Analysis\u003c/h3\u003e\u003cp\u003eMultivariate Cox regression analysis was used to demonstrate the effect of each variable (e.g., age, menstrual status, treatment modality, tumor characteristics, etc.) on the OS (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). It shows that age, tumor size, HER2 status, and metastatic site all have a significant impact on the survival of breast cancer patients. In contrast, age grouping of 35–54 (HR = 0.77, [95% CI: 0.63–0.94], p = 0.01) and HER2 + status (HR = 0.77, [95% CI: 0.65–0.91], p = 0.0019) were significantly associated with a lower risk of death. T2 group (HR = 1.3, [95% CI: 1-1.7], p = 0.033), T4 group (HR = 2, [95% CI: 1.5–2.6], p \u0026lt; 0.0001), brain metastases group (HR = 1.8, [95% CI: 1.3–2.6], p = 0.00094), hepatic metastases group (HR = 3.6, [95% CI: 1.7–7.3], p = 0.00051) and multisite metastases group (HR = 2.7, [95% CI: 2.3–3.2], p \u0026lt; 0.0001) were significantly associated with a higher risk of death.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCompared with early-stage breast cancer, \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer is inherently more aggressive and carries a poorer prognosis, making its management a significant clinical challenge. In addition, in recent years, there has been controversy over whether surgical intervention of the primary tumor should be performed for \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer.\u003c/p\u003e \u003cp\u003eThis study provides information on the clinicopathologic of patients who underwent surgery for \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer in China and the US. Our analysis revealed substantial differences in clinicopathologic characteristics and treatment patterns between the two cohorts. Compared with the SEER database, the NCCOID database recorded a higher proportion of younger patients, whereas the SEER database had a larger proportion of patients aged 55 years and older. In fact, Chinese women generally develop breast cancer at a younger age and are more willing to go for surgical treatment, whereas Western women tend to develop breast cancer after menopause [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], which is consistent with the epidemiological profile of breast cancer in Asian populations with a forward shift in the age of onset of the disease [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In the present study, the proportions of T-stages in the two cohorts also differed considerably, with a significantly higher proportion of T2-stage patients in NCCOID and a more prominent proportion of T4-stage patients in SEER. In some Chinese clinical practices, surgeons tend to prioritize early surgical control of the primary tumor in stage IV patients with T1-T2 disease and oligometastases, provided the patient\u0026rsquo;s systemic condition remains stable. This approach aims to mitigate the risk of local complications (e.g., rupture or infection) associated with tumor progression. As for the US, more emphasis is placed on systemic therapy as the mainstay of treatment, and for these patients, targeted, endocrine, or chemotherapy may be given first to observe the efficacy of the treatment and palliative surgery will be considered only when the T-stage is large and the local symptoms are obvious[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In this case, surgery may be used as a means of controlling local symptoms rather than prolonging survival [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In terms of the metastatic pattern, bone metastasis was the most common single type of metastasis in both groups of patients. Bone metastases are often associated with the HR\u0026thinsp;+\u0026thinsp;subtype, progress more slowly, and are capable of better survival outcomes [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study highlights a stark contrast in the adoption of surgical treatments between the two cohorts. While mastectomy remains the predominant surgical approach in both databases, the use of BCS is significantly higher in the US cohort. This could be attributed to the different treatment guidelines and patient preferences in each country, influenced by the availability of healthcare resources and the extent of public health education regarding breast cancer treatments. Although the majority of patients with \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer undergo mastectomy, studies by Khan et al [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and Kommalapati et al [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] have found that patients who undergo partial mastectomy with clear negative margins achieve the same OS rate and that both surgical procedures prolong patient survival compared with no surgery. A meta-analysis [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] that included 216,066 patients with new stage IV breast cancer similarly showed that both margin-negative BCS and mastectomy could be options for local management in such patients, but positive margins did not improve survival. Another study [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] showed that the 5-year OS rate was 13% in patients who did not undergo surgery on the primary site, 16% in patients who underwent surgery but had positive margins, and 27% in patients who underwent surgery with negative margins. Therefore, both BCS with negative margins and mastectomy can be used as optional surgical procedures for these patients.\u003c/p\u003e \u003cp\u003eThere were significant differences in the use of preoperative and postoperative systemic therapy between the two groups, suggesting a difference in the choice of timing of surgery between China and the US. A higher proportion of Chinese patients received preoperative systemic therapy, which may reflect a more aggressive treatment strategy in China, possibly due to a higher tumor load at diagnosis and the need to control systemic disease before local intervention. Patients who respond well to initial systemic therapy (chemotherapy, hormonal therapy, or targeted therapy) may be candidates for surgery [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Currently, there is no conclusive evidence on the timing of surgery for stage IV breast cancer. There are differences in the design and patient selection of several randomized controlled trials, with the TATA study [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], the EA2108 study [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] performing systemic therapy first and local surgery for patients who are sensitive to systemic therapy, and the MF07-01 study [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] adopting a more aggressive treatment strategy, with surgery followed by systemic therapy. Notably, a retrospective analysis in the United States [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] suggested that delayed surgery (\u0026gt;\u0026thinsp;3 months after diagnosis) may be associated with improved progression-free survival (PFS). A domestic study [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] further confirmed that primary resection reduces breast cancer-specific mortality regardless of the timing of surgery (before or after systemic therapy), and this benefit is particularly significant in a specific oligometastatic population (bone/lung/liver metastases and no brain metastases).\u003c/p\u003e \u003cp\u003eSeveral retrospective studies [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] have shown that surgical treatment of primary tumors improves the prognosis of patients with \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer, but the effects of patient heterogeneity and tumor subtype need to be taken into account, and the results of randomized clinical trials have not been consistently conclusive due to the rationalization of the development of systemic treatment regimens. Our subgroup analyses further demonstrated which types of patients benefit more from surgical treatment. For example, we found that younger patients benefited more, whereas older patients typically had lower survival rates, a result also reflected in the SEER data. In addition, ER\u0026thinsp;+\u0026thinsp;patients consistently showed better survival rates, possibly because ER\u0026thinsp;+\u0026thinsp;patients were able to receive endocrine therapy to slow or inhibit tumor growth, responded better to treatment, had a lower risk of disease progression, and therefore had a better prognosis [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis is the same conclusion obtained from previous studies. The subgroup analysis of the MF07-01 study showed that patients with HR+, HER2-, age\u0026thinsp;\u0026lt;\u0026thinsp;55 years, and bone metastases only could benefit from localized therapy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Hou et al. included 11974 patients with primary stage IV breast cancer from the SEER database and showed that HR+/HER2\u0026thinsp;+\u0026thinsp;patients had the best prognosis, while HR -/HER2- patients had the worst prognosis [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. A subgroup analysis of the JCOG1017 study demonstrated the same results, with improved overall survival for patients with ER-positive, premenopausal status, and single-organ metastases [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, in a separate report on the outcomes of the TBCRC 013 trial by Prof. Tari A. King of the Dana-Farber Cancer Center, it was determined that the primary prognostic factor in patients with stage IV disease is the efficacy of first-line treatments. In addition, the impact of localized surgery may be relatively minor in patients who respond well to treatment. Thus, developing a surgical plan should be a collaborative process involving medical oncologists, surgeons, and the patients themselves [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Our findings support a tailored treatment strategy, in which surgical decisions are guided by individual patient profiles and tumor biology, rather than applying uniform management. This strategy could maximize the therapeutic benefits while minimizing unnecessary interventions.\u003c/p\u003e \u003cp\u003eLimitation\u003c/p\u003e \u003cp\u003eFirst, this study is a retrospective real-world analysis, and further prospective clinical studies are needed to establish whether surgery can offer improved survival benefits. Second, according to the corresponding datasets, the data sources and inclusion criteria differ between China and the US. Third, due to an inadequate cancer data registry system that leads to missing information, variables, and data with significant gaps are excluded.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, the management of stage IV breast cancer requires careful consideration of multiple prognostic variables, including demographic factors, tumor biology, and treatment strategies. Our study provides a comprehensive comparison of how these elements interact within and between different healthcare systems, offering a direction for future research and policy-making to improve outcomes for this challenging patient population. Our findings suggest that select patients\u0026mdash;particularly those with HR\u0026thinsp;+\u0026thinsp;disease, limited tumor burden, oligometastatic presentation, and favorable response to systemic therapy\u0026mdash;may derive survival benefits from surgical intervention when R0 resection is achievable. Further studies are needed to refine the criteria for surgical candidacy in this group and to optimize systemic treatment protocols, aiming for the best possible quality of life and survival outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADCs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eantibody-drug conjugates\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBCS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebreast-conserving surgery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHER2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehuman epidermal growth factor receptor 2\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehormone receptor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMICE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMultiple Imputation by Chained Equations\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNCCOID\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational Cancer Center of China Tumor Information Database\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational Cancer Institute\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eoverall survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePFS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprogression-free survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSEER\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSurveillance,Epidemiology,and End Results\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research was funded in part by the National Natural Science Foundation of China (Grant No. 82272938 to Jiaqi Liu), the Beijing Nova Program of Science and Technology (Grant No. 20220484059 to Jiaqi Liu), and the CAMS Innovation Fund for Medical Sciences (Grant No. 2021-I2M-1-014 to Jiaqi Liu and Xiang Wang).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eDongxu Ma: Writing - original draft, Methodology, Formal analysis, Investigation, Data curation. Heng Cao: Writing - original draft, Formal analysis, Visualization. Jiang Wu: Writing - original draft, Data curation. Tongxuan Shang: Data curation. Zizhao Guo: Data curation. Lin Cong: Data curation. Ziqi Jia: Data curation. Yuchen Liu: Data curation. Jiaqi Liu: Writing\u0026ndash;review \u0026amp; editing, Supervision, Conceptualization. Xiang Wang: Writing\u0026ndash;review \u0026amp; editing, Supervision, Conceptualization.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.\u003c/p\u003e \u003cp\u003eEthical approval\u003c/p\u003e \u003cp\u003e The study was approved by the Ethics Committees of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College (No. 23/026-3765).\u003c/p\u003e \u003cp\u003eConflicts of interest\u003c/p\u003e \u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e \u003cp\u003eAcknowledgments\u003c/p\u003e \u003cp\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSiegel, R.L., A.N. Giaquinto, and A. 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While systemic therapy remains the cornerstone of treatment, the role of surgical intervention for the primary tumor remains controversial. This study aimed to compare surgical treatment patterns and survival outcomes in \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer patients between China and the United States using two large-scale national databases, to inform personalized treatment strategies and future guideline development.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis multicenter, retrospective cohort study included \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer patients who underwent surgery from the National Cancer Center Oncology Information Database (NCCOID) and the Surveillance, Epidemiology, and End Results (SEER) database. The two cohorts were compared in clinical characteristics, treatment strategies, and survival outcomes. Kaplan-Meier analysis and multivariate Cox regression were used to identify factors associated with overall survival (OS).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 2,037 patients from China (2013\u0026ndash;2020) and 3,175 from the US were included. Compared to SEER, the NCCOID cohort had a higher proportion of younger patients and more cases of T2-stage tumors. Mastectomy was the predominant surgical method in both countries, though breast-conserving surgery (BCS) was more common in the US. Chinese patients were more likely to receive preoperative systemic therapy. The NCCOID cohort showed superior OS (1-year: 91.5%, 3-year: 77.4%, 5-year: 67.9%) compared to SEER (1-year: 87.7%, 3-year: 62.8%, 5-year: 46.4%). Subgroup analyses revealed better survival in patients with HR\u0026thinsp;+\u0026thinsp;status, T-staging for smaller tumors, and bone-only metastases. Multivariate Cox regression confirmed that younger age (35\u0026ndash;54), HR\u0026thinsp;+\u0026thinsp;status, HER2\u0026thinsp;+\u0026thinsp;status, and limited metastases (especially bone-only metastases) were independently associated with improved OS.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSurgical treatment for \u003cem\u003ede novo\u003c/em\u003e stage IV breast cancer is approached differently in China and the US, with variations in patient age, tumor characteristics, and systemic therapy timing. Selected patients\u0026mdash;particularly those with HR\u0026thinsp;+\u0026thinsp;tumors, HER2\u0026thinsp;+\u0026thinsp;tumors, smaller primary lesions, and limited metastases\u0026mdash;may benefit from surgical resection. These findings support a personalized approach to surgery, emphasizing multidisciplinary decision-making. Prospective studies are needed to validate optimal surgical timing and patient selection.\u003c/p\u003e","manuscriptTitle":"Analysis of the Current Status of De Novo Stage IV Breast Cancer Surgery in China and the United States: A multicenter real-world study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-16 11:55:16","doi":"10.21203/rs.3.rs-6598564/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d6e2abec-1105-47ca-9a98-18cf8d8b6c07","owner":[],"postedDate":"May 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-26T09:24:58+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-16 11:55:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6598564","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6598564","identity":"rs-6598564","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}