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Published: Mon 11, Aug 2025
Received: Thu 10, Apr 2025
Accepted: Mon 26, May 2025

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Ang Zheng Feng Jin Junnan Cao Mengyang Pang Muyao Li Shiqi Jiang Weitao Wang Xinzhu Hu Ziyao Ji

Abstract

Background: De novo stage IV breast cancer is defined as breast cancer with distant metastases at the time of diagnosis, which is incurable. It is crucial for clinicians to understand all the prognostic factors to make a more accurate judgement for clinical practice.
Aim: Identify protective and risk factors, and explore benefits of specific palliative care for de novo stage IV breast cancer patients.
Design: The protocol was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) with the registration number 202270053. The Newcastle-Ottawa scale was used to assess the quality of the studies. Hazard ratios for overall survival (OS), breast cancer-specific survival (BCSS), and progression-free survival (PFS) were calculated using fixed or random effect models.
Data Sources: The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for observational studies on prognostic factors for de novo stage IV breast cancer.
Results: A meta-analysis of 30 studies showed that protective factors included being married, Asian ethnicity, hormone receptor status, hormone receptor+/human epidermal growth factor receptor 2 (HER2)+, palliative surgery for the primary tumour and palliative radiotherapy. Survival risk factors included advanced age, black ethnicity, advanced T-stage, lymphatic metastases, high histological grade, hormone receptor-/HER2-, lobular carcinoma, metastases, and high-risk category of 21 gene panel.
Conclusions: This study identifies protective and risk factors for survival in patients with de novo stage IV breast cancer and provides new evidence to facilitate precision diagnosis and personalised treatment of this disease.

Keywords

de novo stage IV breast cancer, protective factor, risk factor, progression-free survival, breast cancer-specific survival

What is already known about the topic?

• Clinician predicted survival for cancer patients is often used in clinical practice, but research shows that it tends to be inaccurate.
• It is critical to improve the quality of life in patients with de novo stage IV breast cancer by improving the accuracy of prognostic estimates. However, predicting prognosis of de novo stage IV breast cancer is more reliant on clinician predicted survival due to a lack of recognised prognostic factor.
• Other systematic reviews only descriptively analyse prognositic factors in de novo stage IV breast cancer, without using meta-analyses. It is difficult for clinicians to understand all the influencing factors to make a more accurate judgment, calling for an updated systematic review and meta-analysis utilising the most recent research and well-established methodologies.

What this paper adds?

• The protective factors for survival in patients with de novo stage IV breast cancer included being married, Asian race, hormone receptor status, hormone receptor+/HER2+, palliative surgery on the primary tumor and palliative radiotherapy.
• The risk factors for survival in patients with de novo stage IV breast cancer were advanced age, black race, advanced T-stage, lymphatic metastasis, high histological grade, hormone receptor -/HER2-, lobular carcinoma, metastases, and high risk category of 21 gene panel.

Implications for practice, theory or policy

• This study identified prognostic factors in patients with de novo stage IV breast cancer, which will be helpful for improving precision diagnostics and delivering personalized treatment.
• This study explored whether palliative surgery or radiotherapy could clinically benefit patients with de novo stage IV breast cancer.
• A meta-analysis can be used to cross-check clinician predicted survival and to provide an objective survival estimate.

1. Introduction

Breast cancer is the most common cancer among women worldwide and in China [1, 2]. De novo stage IV breast cancer refers to breast cancer with distant metastasis at the time of diagnosis and accounts for 6-10% of all diagnosed cases of breast cancer [3]. De novo stage IV breast cancer accounts for 1.07% of first-visit outpatients in Chinese breast surgery departments, with a median age of 51.5 years [4]. Early breast cancer is considered to be a curable disease, but most of de novo stage IV breast cancer is incurable and belongs to palliative disease. Improving the quality of life and prolonging the survival time are the basic principles.

More than 60% of patients in the United States survived for more than two years and 17% survived for more than ten years [5]. Some observational studies have suggested that patients with de novo stage IV breast cancer may have better survival outcomes than those with recurrent metastatic disease [6]. De novo stage IV breast cancer patients comprise a heterogeneous group of patients with vastly different prognoses. For those with de novo stage IV breast cancer, the decision to select aggressive therapy or palliative care is complex, and it depends greatly on clinician predicted survival [7]. It is critical to improve the quality of life in patients with de novo stage IV breast cancer by improving the accuracy of prognostic estimates [8]. However, predicting prognosis of de novo stage IV breast cancer is more reliant on clinician predicted survival due to a lack of recognised prognostic factors, unlike earlier in the course of the breast cancer where survival is known to rely on disease stage, tumour type and availability of treatment [9]. This study identified prognostic factors in patients with de novo stage IV breast cancer, which will be helpful for improving precision diagnostics and delivering personalized treatment.

This is despite the current expert consensus that resection of the primary site may not improve survival in patients with de novo stage IV breast cancer. However, we have seen conflicting results in prospective and retrospective studies, which may suggest that some patients who meet certain criteria may still have a survival benefit from palliative surgical treatment or radiotherapy. Current evidence suggests that, in addition to the possible extension of survival in patients with simple bone metastases, no clear survival benefit has been seen in de novo stage IV breast cancer who have had their primary tumor removed. However, in cases where the metastasis is small and systemic treatment is effective, palliative surgery may also be considered in specific patients, especially if the goal is to improve quality of life, and the patient's preferences should always be taken into account. At present, the evidence mainly comes from retrospective studies, and the conclusions of several small-scale prospective clinical trials are inconsistent [10, 11]. This study explored whether palliative surgery or radiotherapy could clinically benefit patients with de novo stage IV breast cancer.

Other systematic reviews only descriptively analyse prognositic factors in de novo stage IV breast cancer, without using meta-analyses. It is difficult for policymakers and clinicians to understand all the influencing factors to make a more accurate judgment. The objectives of this study were: i) to identify protective and risk factors in patients with de novo stage IV breast cancer and ii) to explore whether specific palliative treatment could benefit patients with de novo stage IV breast cancer.

2. Methods

2.1. Literature Collection

This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines [12]. The protocol was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) with the registration number 202270053. Literature searches were also conducted using PubMed, the Cochrane Library, EMBASE, and Web of Science. Medical subject headings (MeSH) and free-text terms were used to search for disease types (for diseases without MeSH terms, free-text keywords were used as search terms). The search strategy details are provided in supplementary material. Additionally, the reference lists of the selected studies were manually searched to ensure completeness of the literature search. The literature search was independently conducted, and a consensus was reached through discussion in cases of disagreement.

2.2. Inclusion and Exclusion Criteria

The inclusion criteria were as follows: i) the patient was diagnosed with de novo stage IV breast cancer at a medical institution, ii) the patient was a case‒control study or cohort study, iii) relevant studies included prognostic factors mentioned in at least two studies, and iv) the odds ratio (OR)/hazard ratio and 95% confidence interval (CI) were available or sufficient data were available.

The exclusion criteria were as follows: i) duplicate publications; ii) papers including reviews, meta-analyses, case reports, or animal studies; iii) unavailable full text, incomplete data, or improper statistical methods; and iv) a Newcastle-Ottawa Scale (NOS) score < six.

2.3. Data Extraction and Quality Assessment

We extracted information about the first author’s name, year of publication, country, type of study, study design, number of patients, and influencing factors from the included studies. The NOS recommended by the Cochrane Collaboration was used for literature quality assessment [13]. Higher scores indicated better quality of the included literature. The NOS was performed independently by two researchers, and a third researcher made the final decision in case of disagreement. The detailed characteristics of the included studies are presented in (Table 1). A summary of influenced factors based on different endpoints is shown in (Table S1-S7 in Supplementary File).

TABLE 1: Characteristics of the studies and population in the included articles.

2.4. Endpoints

De novo stage IV breast cancer was defined as the presence of metastasis at the time of primary tumor diagnosis or within 6 months [14]. OS was defined as the time from the date of diagnosis to the date of death from any cause. The BCSS was defined as the time from the date of diagnosis to the date of death from breast cancer. PFS was defined as the time from the initial diagnosis to distant progression or death.

2.5. Statistical Analysis

Review Manager 5.3 software (Cochrane Collaboration, Copenhagen, Denmark) was used in this study. The Cochrane Q test was used to analyze heterogeneity. When P was > 0.1 and I² was < 50%, no statistical heterogeneity existed between the studies. Accordingly, a fixed effects model was used. If statistical heterogeneity was found, sensitivity analysis was used to identify the source of heterogeneity; otherwise, a random effects model was used, and forest plots were generated to display the final results. Publication bias was assessed to analyze influencing factors included in five or more studies. P > 0.05 indicated no obvious publication bias according to Egger’s test or Begg’s test. P<0.05 was considered to indicate statistical significance.

3. Results

3.1. Study Selection and Study Quality

We retrieved 3310 studies from PubMed, the Cochrane Library, EMBASE, and the Web of Science, respectively. In addition, two studies were found using other sources, resulting in a total of 3312 studies. Of these, 164 duplicate studies were removed. After eliminating 2957 irrelevant studies, the remaining 62 studies, whose full texts were downloaded, were carefully evaluated. The final analysis included 30 original studies [15-44] (Figure 1). Of the 30 studies published between 2006 and 2024, 21 factors were entered into the meta-analysis. The NOS scores of the 30 studies ranged from six to nine, indicating that the quality of the studies was high, as shown in (Supplemental Table S1).

3.2. Basic Patient Characteristics

The analysis showed that I² = 0% (I² < 50%) and P = 0.76. Therefore, a fixed-effects model was applied. From the forest map, advanced age was associated with poor OS among de novo stage IV breast cancer patients (age > 50 vs. age ≤ 50, hazard ratio (HR) = 1.49, 95% CI, 1.36-1.63; age > 40 vs. age 18-40, HR = 1.69, 95% CI = 1.39-2.05, P < 0.00001) (Figures 2A & 2B). Similarly, advanced age was associated with poor BCSS among de novo stage IV breast cancer patients (age > 40 vs. age 18-40, HR = 1.45, 95% CI = 1.10-1.92, P = 0.008) (Supplemental Figure 1A). Being married was a protective factor for BCSS (HR = 0.83, 95% CI=0.76-0.90, P < 0.00001) (Supplemental Figure 1B) and OS (HR = 0.80, 95% CI = 0.78-0.82, P < 0.00001) (Figure 2C). Health insurance coverage failed to affect OS (HR = 0.71, 95% CI = 0.50-1.01, P = 0.06) (Figure 2D). A black race was a risk factor affecting BCSS and OS in patients with de novo stage IV breast cancer (HR = 1.17, 95% CI = 1.14-1.20, P < 0.0001; HR = 1.16, 95% CI = 1.13-1.20, P < 0.00001) (Supplemental Figure 1C & Figure 2E). We surprisingly found that Asian race was a protective factor affecting OS in patients with de novo stage IV breast cancer (HR=0.68, 95% CI=0.47-0.97, P=0.04) (Figure 2F).

3.3. Characteristics of the Primary Tumor

Furthermore, we analyzed characteristics of the primary tumor influenced the survival of de novo stage IV breast cancer patients. Hormone receptor positive was a protective factor for BCSS (HR = 0.53, 95% CI = 0.40-0.69, P < 0.00001) (Supplemental Figure 1D) and OS (HR = 0.58, 95% CI = 0.51-0.67, P < 0.00001) (Figure 3A). Advanced T-stage and N-stage were risk factors affecting OS. (N0 vs. N1/2/3, HR = 1.29, 95% CI = 1.09-1.53, P = 0.003; T0 vs. T1/2/3, HR = 0.68, 95% CI = 0.62-0.76, P < 0.00001; T1 vs. T2/3/4, HR = 1.42, 95% CI = 1.16-1.74, P = 0.0007) (Figures 3B-3D). Similarly, advanced T-stage was a risk factor affecting BCSS (T0-1 vs. T4, HR = 1.35, 95% CI = 1.25-1.46, P < 0.00001) (Supplemental Figure 1E). High histological grade was a risk factor affecting BCSS and OS (BCSS, HR = 1.77, 95% CI = 1.50-2.09, P < 0.00001; OS, HR = 1.55, 95% CI = 1.29-1.87, P < 0.00001) (Supplemental Figure 1F & Figure 3E). When hormone receptor -HER2+ was used as the control group, hormone receptor -HER2- was a risk factor for BCSS (HR = 2.41, 95% CI = 2.09-2.78, P < 0.00001) and OS (HR = 2.62, 95% CI = 2.27-3.02, P < 0.0001); and hormone receptor +HER2+ was a protective factor for BCSS (HR = 0.71, 95% CI = 0.67-0.76, P < 0.00001) and OS (HR = 0.74, 95% CI = 0.65-0.84, P < 0.0001) in patients with de novo stage IV breast cancer (Supplemental Figure 1G & Figure 3F). Furthermore, hormone receptor -HER2- was a risk factor for PFS (HR = 1.57, 95% CI = 1.25-1.97, P < 0.0001) in patients with de novo stage IV breast cancer (Supplemental Figure 3A & Figure 3G). When infiltrating duct carcinoma (IDC) was used as the control group, lobular carcinoma were risk factors for BCSS (HR = 1.24, 95% CI = 1.16-1.33, P < 0.00001) and OS (HR = 1.23, 95% CI = 1.18-1.29, P < 0.0001) in patients with de novo stage IV breast cancer (Supplemental Figure 1H & Figure 3G).

3.4. Characteristics of Metastasis

As to metastatic sites, metastases to the specific organs (including brain, bone, liver and lung, etc) indicated poorer BCSS and OS among de novo stage IV breast cancer patients (bone metastasis: BCSS: HR = 1.26, 95% CI = 1.06-1.50, P = 0.009; OS: HR = 1.39, 95% CI = 1.26-1.54, P < 0.00001; brain metastasis: BCSS: HR = 2.50, 95% CI = 1.71-3.65, P < 0.00001; OS: HR = 2.08, 95% CI = 1.58-2.73, P < 0.00001; liver metastasis: BCSS: HR = 1.53, 95% CI = 1.37-1.71, P < 0.00001; OS: HR = 1.82, 95% CI = 1.44-2.30, P < 0.00001; lung metastasis: BCSS: HR = 1.32, 95% CI = 1.12-1.57, P = 0.001; OS: HR = 1.41, 95% CI = 1.18-1.69, P = 0.0002) (Supplemental Figures 2A-2D & Figures 4A-4D). There was no significant difference in the benefit of OS between bone metastasis and brain metastasis (HR = 2.33, 95% CI = 0.91-6.00, P = 0.08) (Figure 4E). The presence of more than one metastatic site was a risk factor for OS (HR = 1.53, 95% CI = 1.39-1.69, P < 0.00001) (Figure 4F).

3.5. Palliative Treatment

Our analysis confirmed that primary tumor resection was associated with increased OS, PFS and BCSS for patients without no surgery (OS, HR = 0.57, 95% CI = 0.54-0.61, P < 0.00001; PFS, HR = 0.69, 95% CI = 0.51-0.78, P < 0.0001; BCSS, HR = 0.63, 95% CI = 0.54-0.73, P < 0.0001) (Supplemental Figures 2E & 3B and Figure 5A).Treatment with radiotherapy was a protective factor for OS and PFS (OS, HR = 0.93, 95% CI = 0.89-0.97, P = 0.0003; PFS, HR = 0.68, 95% CI = 0.59-0.77, P < 0.00001) (Supplemental Figure 3C and Figure 5B).

3.6. 21 Gene Panel

Our analysis confirmed that high risk category of 21 gene panel was associated with decreased OS (OS, HR = 1.94, 95% CI = 1.32-2.84, P = 0.0007) (Figure 6).

3.7 Publication Bias

The funnel plots were largely symmetrical showed that there was no significant publication bias for the outcome (Supplemental Figure S4).

4. Discussion

4.1. Main Findings

This study found that being married was associated with improved survival, suggesting a potential role of family and social support in influencing prognosis in patients with de novo stage IV breast cancer. De novo stage IV breast cancer places great economic burden and psychological pressure on patients. At present, the concept of systemic treatment for de novo stage IV breast cancer has gained consensus. Long-term systemic therapy has resulted in high treatment costs. Along with this, tests and lab work costs are high. The total cost of treatment is often difficult to predict. Family support had a positive impact on improving treatment compliance in de novo stage IV breast cancer patients in terms of home care, psychological support, financial support, and medication accessibility.

Concerning age, advanced age was a risk factor affecting the prognosis of patients with de novo stage IV breast cancer. De novo stage IV breast cancer was commonly associated with one or more systemic diseases. Patients with de novo stage IV breast cancer were poorly tolerant of standard therapies such as chemotherapy and can only accept palliative treatment. The treatment compliance of the elderly patients was poor. Black patients with de novo stage IV breast cancer have a much greater risk of death than other races, while Asian patients are likely to have better survival. Whether this difference comes from genetic differences between races or social determinants that influence access and quality of care is worth investigating.

Additionally, advanced T-stage, lymphatic metastasis, high histological grade, and lobular carcinoma were risk factors in this study. Therefore, the presence of axillary lymph node metastases was indicative of poor prognosis in patients with de novo stage IV breast cancer. Furthermore, this suggested that palliative management of lymph nodes might be necessary when the axillary lymph nodes are metastatic. Only retrospective studies have indicated that axillary lymph node dissection has no statistically significant effect on survival in patients with de novo stage IV breast cancer. There were no clinical trials with a primary research objective of investigating the effect of axillary lymph node dissection on prognosis [45-47]. Patients with hormone receptor-positive and HER2-positive (HR+/HER2+) de novo stage IV breast cancer tend to have the most favorable prognosis. This is largely due to the effectiveness of combining HER2-targeted therapies (such as trastuzumab and pertuzumab) with endocrine treatments. These regimens target both HER2 and estrogen receptor pathways, resulting in synergistic inhibition of tumor growth. Clinical trials such as CLEOPATRA and PERTAIN have shown significant survival benefits with such combined strategies. Triple-negative de novo stage IV breast cancer patients had the worst prognosis, which was similar to that of triple-negative breast cancer patients at other stages.

Among the metastatic sites, more than one metastatic site and specific metastasis were risk factors for patients with de novo stage IV breast cancer. This means that patients with a high metastatic burden have a relatively poor prognosis, supporting the delivery of advanced systemic treatment and relatively aggressive local therapy [11]. We did not find sufficient literature to conduct a meta-analysis on the survival benefit of palliative metastatic surgery. A study of 86 patients with liver metastasis of breast cancer found that the survival of those who underwent complete resection of liver lesions after systemic treatment was effective was significantly improved [48]. A retrospective study also suggested that resection of metastases in de novo breast cancer may be associated with improved survival, especially in patients with lung or liver involvement [18]. Other studies have found that patients with fewer metastases and positive hormone receptors are more likely to benefit from resection of lung or liver metastases [49-52].

4.2. What This Study Adds?

Most of de novo stage IV breast cancer belongs to palliative disease, so the treatment is considered as palliative treatment. The objective of surgical treatment should be to resolve comorbidities that seriously affect patients' quality of life, reduce tumor burden, and obtain R0 resection of primary and/or distant lesions. Whether palliative surgery on primary tumors for de novo stage IV breast cancer can provide clinical benefits in terms of effective systemic treatment and stable conditions has attracted considerable interest. However, the lack of data from high-level prospective studies make clinical treatment decision-making challenging. This meta-analysis revealed that surgery on primary tumors significantly improved PFS, BCSS, and OS. Here, PFS was added to the analysis because it required a short follow-up time and was not affected by crossover or follow-up treatments, allowing for objective and quantitative assessment of clinical benefit. In the MF07-01 trial, the results of a 10-year follow-up suggested that the OS was significantly longer in the group receiving local treatment followed by systemic treatment than in the group receiving systemic treatment only [53]. Patients in specific groups with de novo stage IV breast cancer may benefit from surgery on the primary tumor, such as patients with triple-negative breast cancer (TNBC) with a single metastasis [54, 55]. A study on the long-term survival of 24,015 patients with de novo stage IV breast cancer also showed similar results [56].

However, prospective studies have reached different conclusions. The results of a 3-year follow-up study in the TBCRC013 trial showed that patients who received effective first-line systemic therapy tended to achieve better OS, and surgery did not improve PFS for any molecular subtype [41]. The latest EA2108 clinical trial randomized 256 patients with de novo stage IV breast cancer who were effectively treated with systemic therapy into two groups. Local treatment in combination with systemic treatment did not change survival outcomes [45]. Retrospective analyses often include patients with lower tumor burden, fewer metastatic sites, and better overall health. These favorable characteristics may independently correlate with better outcomes, which could falsely amplify the perceived benefit of surgery. Most prospective trials, such as EA2108, only include patients who respond to systemic therapy. While this reflects real-world practice, it may paradoxically reduce the measurable added value of local interventions, since the prognosis is already improved by systemic control. In trials like TBCRC013 and EA2108, surgery is performed after systemic therapy. This delayed intervention may not influence micrometastatic disease that has already been stabilized or is progressing, compared to upfront surgery in retrospective designs.Retrospective data often span long periods with inconsistent or outdated systemic regimens, while prospective studies use more contemporary, uniform treatments (e.g., HER2 dual blockade, CDK4/6 inhibitors). This evolution may diminish the relative effect size of local therapy in modern settings.Trial designs vary significantly in surgical criteria, metastatic burden, and endpoints (OS vs. PFS), which complicates cross-study comparisons and leads to inconsistent results.

Radiotherapy was also a common palliative treatment for de novo stage IV breast cancer patients. It was unclear whether surgery-based adjuvant radiotherapy improved patient survival [57, 58]. This study added new evidence to the prognostic significance of radiotherapy in patients with de novo stage IV breast cancer. The results suggested that palliative radiotherapy improved OS and PFS in patients with de novo stage IV breast cancer.

The 21-gene RS is a widely recognized genomic tool that has primarily been used in early-stage BC patients with nodenegative disease (N0) or one to three lymph nodes (N1) to predict the risk of disease recurrence and guide treatment decisions [59]. While initially designed for early-stage BC, there is growing interest in exploring the utility of the RS in other BC subgroups, including those with four or more lymph nodes (N2) or HER2-positive disease [60, 61]. To the best of our knowledge, limited data exist regarding its utility and validity in patients with de novo stage IV breast cancer [41]. Our study revealed a significant correlation between the RS and prognosis in de novo stage IV breast cancer.

4.3. Strengths and Limitations of the Study

The strengths of this review are that it is currently the most comprehensive analysis of various factors influencing the prognosis of patients with de novo stage IV breast cancer, providing new evidence to promote precision diagnostics and personalized treatment of this disease. The detailed portrayal of patient situations and influencing factors, along with a wealth of cited literature support, adds credibility to the findings. Additionally, the article's discussion on the clinical significance of palliative surgery or radiotherapy and its comparative analysis of various factors impacting patient outcomes offer crucial insights for clinical decision-making.

This paper has some limitations. Some of the influencing factors exhibited unavoidable heterogeneity during the data analysis due to the insufficient number of studies included. Furthermore, several potential influencing factors were mentioned in only a single publication. Income, menopausal status, miR-106b expression, and metastasectomy may be potential factors influencing the prognosis of de novo stage IV breast cancer patients. therefore, more definite conclusions could not be drawn [18, 32, 62, 63].

4.4. Implications for Research

It is useful for policymakers and clinicians to understand these influencing factors to make a more accurate judgment, to identify protective and risk factors in patients with de novo stage IV breast cancer and to explore whether specific palliative treatment could benefit patients with de novo stage IV breast cancer.

5. Conclusion

This meta-analysis identified protective and risk factors affecting survival in patients with de novo stage IV breast cancer, providing new evidence and insights to promote precision diagnostics and the delivery of personalized de novo stage IV breast cancer treatment.

Author Contributions

JSQ: Writing - Original draft, visualization. HXZ: Methodology, investigation. PMY: Methodology, investigation. WWT: Investigation. LMY: Editing. CJN: Editing. JF: Editing. JZY: writing - review & editing. ZA: Conceptualization, formal analysis, writing - original draft.

Ethical Approval and Consent

Ethical approval was not required for this review as there was no direct patient contact or access to individual participant data.

Conflicts of Interest

None.

Funding

This study was funded by the Liaoning Provincial Social Science Planning Fund (L22CGL021) , National Natural Science Foundation of China (Grant 82203873) and Beijing Science and Technology Innovation Medical Development Foundation (KC2023-JX-0186-FQ031).

Data Availability Statement

This review searched PubMed, EMBASE, Cochrane Library and Web of Science databases for observational studies on prognostic factors for new stage IV breast cancer. The full search strategy is described in the Supplementary Material. Inclusion/exclusion criteria and quality assessment results are provided in the article. Additional data are available on request.

Acknowledgments

We sincerely thank the Chinese Society of Breast Surgery and Yinhua Liu for their work in this study.

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