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A risk stratification model for predicting brain metastasis and brain screening benefit in patients with metastatic triple-negative breast cancer.

ABSTRACT: BACKGROUND:Patients with metastatic triple-negative breast cancer (mTNBC) frequently experience brain metastasis. This study aimed to identify prognostic factors and construct a nomogram for predicting brain metastasis possibility and brain screening benefit in mTNBC patients. METHODS:Patients with mTNBC treated at our institution between January 2011 and December 2018 were retrospectively analyzed. Fine and Gray's competing risks model was used to identify independent prognostic factors. By integrating these prognostic factors, a competing risk nomogram and risk stratification model were developed and evaluated with concordance index (C-index) and calibration curves. RESULTS:A total of 472 patients were retrospectively analyzed, including 305 patients in the training set, 78 patients in the validation set I and 89 patients in the validation set II. Four clinicopathological factors were identified as independent prognostic factors in the nomogram: lung metastasis, number of metastatic organ sites, hilar/mediastinal lymph node metastasis and KI-67 index. The C-indexes and calibration plots showed that the nomogram exhibited a sufficient level of discrimination. A risk stratification was further generated to divide all the patients into three prognostic groups. The cumulative incidence of brain metastasis at 18 months was 5.3% (95% confidence interval [CI], 2.5%-9.7%) for patients in the low-risk group, while 14.3% (95% CI, 9.3%-20.4%) for patients with intermediate risk and 34.3% (95% CI, 26.8%-41.9%) for patients with high risk. Routine brain MRI screening improved overall survival in high-risk group (HR 0.67, 95% CI 0.46-0.98, P = .039), but not in low-risk group (HR 0.93, 95% CI 0.57-1.49, P = .751) and intermediate-risk group (HR 0.83, 95% CI 0.55-1.27, P = .386). CONCLUSIONS:We have developed a robust tool that is able to predict subsequent brain metastasis in mTNBC patients. Our model will allow selection of patients at high risk for brain metastasis who might benefit from routine bran MRI screening.

SUBMITTER: Lin M

PROVIDER: S-EPMC7666757 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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A risk stratification model for predicting brain metastasis and brain screening benefit in patients with metastatic triple-negative breast cancer.

Lin Mingxi M Jin Yizi Y Jin Jia J Wang Biyun B Hu Xichun X Zhang Jian J

Cancer medicine 20200918 22

<h4>Background</h4>Patients with metastatic triple-negative breast cancer (mTNBC) frequently experience brain metastasis. This study aimed to identify prognostic factors and construct a nomogram for predicting brain metastasis possibility and brain screening benefit in mTNBC patients.<h4>Methods</h4>Patients with mTNBC treated at our institution between January 2011 and December 2018 were retrospectively analyzed. Fine and Gray's competing risks model was used to identify independent prognostic ...[more]

PMID: 32945619

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Project description:Background and Aims: This research aimed to construct a novel model for predicting overall survival (OS) and surgical benefit in triple-negative breast cancer (TNBC) patients with de novo distant metastasis. Methods: We collected data from the Surveillance, Epidemiology, and End Results (SEER) database for TNBC patients with distant metastasis between 2010 and 2016. Patients were excluded if the data regarding metastatic status, follow-up time, or clinicopathological information were incomplete. Univariate and multivariate analyses were applied to identify significant prognostic parameters. By integrating these variables, a predictive nomogram and risk stratification model were constructed and assessed with C-indexes and calibration curves. Results: A total of 1,737 patients were finally identified. Patients enrolled from 2010 to 2014 were randomly assigned to two cohorts, 918 patients in the training cohort and 306 patients in the validation cohort I, and 513 patients enrolled from 2015 to 2016 were assigned to validation cohort II. Seven clinicopathological factors were included as prognostic variables in the nomogram: age, marital status, T stage, bone metastasis, brain metastasis, liver metastasis, and lung metastasis. The C-indexes were 0.72 [95% confidence interval [CI] 0.68-0.76] in the training cohort, 0.71 (95% CI 0.68-0.74) in validation cohort I and 0.71 (95% CI 0.67-0.75) in validation cohort II. Calibration plots indicated that the nomogram-based predictive outcome had good consistency with the recoded prognosis. A risk stratification model was further generated to accurately differentiate patients into three prognostic groups. In all cohorts, the median overall survival time in the low-, intermediate- and high-risk groups was 17.0 months (95% CI 15.6-18.4), 11.0 months (95% CI 10.0-12.0), and 6.0 months (95% CI 4.7-7.3), respectively. Locoregional surgery improved prognosis in both the low-risk [hazard ratio [HR] 0.49, 95% CI 0.41-0.60, P < 0.0001] and intermediate-risk groups (HR 0.55, 95% CI 0.46-0.67, P < 0.0001), but not in high-risk group (HR 0.73, 95% CI 0.52-1.03, P = 0.068). All stratified groups could prognostically benefit from chemotherapy (low-risk group: HR 0.50, 95% CI 0.35-0.69, P < 0.0001; intermediate-risk group: HR 0.34, 95% CI 0.26-0.44, P < 0.0001; and high-risk group: HR 0.16, 95% CI 0.10-0.25, P < 0.0001). Conclusion: A predictive nomogram and risk stratification model were constructed to assess prognosis in TNBC patients with de novo distant metastasis; these methods may provide additional introspection, integration and improvement for therapeutic decisions and further studies.

Project description:BackgroundIncreasing evidence showed that the clinical significance of the interaction between hypoxia and immune status in tumor microenvironment. However, reliable biomarkers based on the hypoxia and immune status in triple-negative breast cancer (TNBC) have not been well established. This study aimed to explore a gene signature based on the hypoxia and immune status for predicting prognosis, risk stratification, and individual treatment in TNBC.MethodsHypoxia-related genes (HRGs) and Immune-related genes (IRGs) were identified using the weighted gene co-expression network analysis (WGCNA) method and the single-sample gene set enrichment analysis (ssGSEA Z-score) with the transcriptomic profiles from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. Then, prognostic hypoxia and immune based genes were identified in TNBC patients from the METABRIC (N = 221), The Cancer Genome Atlas (TCGA) (N = 142), and GSE58812 (N = 107) using univariate cox regression model. A robust hypoxia-immune based gene signature for prognosis was constructed using the least absolute shrinkage and selection operator (LASSO) method. Based on the cross-cohort prognostic hypoxia-immune related gene signature, a comprehensive index of hypoxia and immune was developed and two risk groups with distinct hypoxia-immune status were identified. The prognosis value, hypoxia and immune status, and therapeutic response in different risk groups were analyzed. Furthermore, a nomogram was constructed to predict the prognosis for individual patients, and an independent cohort from the gene expression omnibus (GEO) database was used for external validation.ResultsSix cross-cohort prognostic hypoxia-immune related genes were identified to establish the comprehensive index of hypoxia and immune. Then, patients were clustered into high- and low-risk groups based on the hypoxia-immune status. Patients in the high-risk group showed poorer prognoses to their low-risk counterparts, and the nomogram we constructed yielded favorable performance to predict survival and risk stratification. Besides, the high-risk group had a higher expression of hypoxia-related genes and correlated with hypoxia status in tumor microenvironment. The high-risk group had lower fractions of activated immune cells, and exhibited lower expression of immune checkpoint markers. Furthermore, the ratio of complete response (CR) was greatly declined, and the ratio of breast cancer related events were significantly elevated in the high-risk group.ConclusionThe hypoxia-immune based gene signature we constructed for predicting prognosis was developed and validated, which may contribute to the optimization of risk stratification for prognosis and personalized treatment in TNBC patients.

Dataset Information

A risk stratification model for predicting brain metastasis and brain screening benefit in patients with metastatic triple-negative breast cancer.

Publications

A risk stratification model for predicting brain metastasis and brain screening benefit in patients with metastatic triple-negative breast cancer.

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