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      Prognostic factors and survival prediction in HER2‐positive breast cancer with bone metastases: A retrospective cohort study

      research-article
      1 , 1 ,
      Cancer Medicine
      John Wiley and Sons Inc.
      bone metastasis, breast cancer, HER2, nomogram, prognosis, SEER

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          Abstract

          Background

          Bone is the most common metastatic site of breast cancer. The developmental pattern of bone metastasis differs in different molecular subtypes. The prognostic factors of HER2‐positive breast cancer with bone metastases require further investigation. The goal of this retrospective study was to identify the clinical features and prognostic factors for HER2‐positive patients with bone metastases.

          Methods

          A total of 34,084 HER2‐positive breast cancer cases and 1204 cases of bone metastases from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were analyzed to identify clinical characteristics and prognostic factors. A nomogram was constructed based on the Cox proportional hazards regression model. The C‐index, calibration curve, and receiver operating characteristic (ROC) were utilized for model validation.

          Results

          In the HER2‐positive breast cancer total population (34,084 cases), 6.2% developed metastatic diseases. Bone metastases accounted for 3.5% of the entire cohort and 56.7% of all metastatic cases. Univariate and multivariate Cox regression analyses identified seven prognostic factors for predicting cancer‐specific survival (CSS) for HER2‐positive breast cancer patients with bone metastases, including age, brain metastases, liver metastases, lung metastases, PR status, surgery, and chemotherapy. The C‐index of the nomogram was 0.74 vs. 0.78 (for 3‐year CSS) and 0.77 vs. 0.81 (for 5‐year CSS) in the model and validation cohorts, respectively. The AUCs were 0.74 vs. 0.78 (for 3‐year CSS) and 0.77 vs. 0.81 (for 5‐year CSS) in the model and validation cohorts, respectively. The calibration curves indicated favorable agreement between the actual observations and the predictions.

          Conclusion

          Our study provided population‐based clinical features and prognostic factors for HER2‐positive breast cancer patients with bone metastases and we constructed a prognostic nomogram with reliable accuracy.

          Abstract

          Our study identified prognostic factors and constructed a prognostic model for HER2‐positive patients with bone metastases. Seven prognostic factors of predicting cancer‐specific survival (CSS) for HER2‐positive breast cancer patients with bone metastases were identified, including age, brain metastases, liver metastases, lung metastases, PR status, surgery, and chemotherapy.

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          Most cited references38

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†

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              Use and misuse of the receiver operating characteristic curve in risk prediction.

              The c statistic, or area under the receiver operating characteristic (ROC) curve, achieved popularity in diagnostic testing, in which the test characteristics of sensitivity and specificity are relevant to discriminating diseased versus nondiseased patients. The c statistic, however, may not be optimal in assessing models that predict future risk or stratify individuals into risk categories. In this setting, calibration is as important to the accurate assessment of risk. For example, a biomarker with an odds ratio of 3 may have little effect on the c statistic, yet an increased level could shift estimated 10-year cardiovascular risk for an individual patient from 8% to 24%, which would lead to different treatment recommendations under current Adult Treatment Panel III guidelines. Accepted risk factors such as lipids, hypertension, and smoking have only marginal impact on the c statistic individually yet lead to more accurate reclassification of large proportions of patients into higher-risk or lower-risk categories. Perfectly calibrated models for complex disease can, in fact, only achieve values for the c statistic well below the theoretical maximum of 1. Use of the c statistic for model selection could thus naively eliminate established risk factors from cardiovascular risk prediction scores. As novel risk factors are discovered, sole reliance on the c statistic to evaluate their utility as risk predictors thus seems ill-advised.
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                Author and article information

                Contributors
                luobin@mail.tsinghua.edu.cn
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                06 October 2021
                November 2021
                : 10
                : 22 ( doiID: 10.1002/cam4.v10.22 )
                : 8114-8126
                Affiliations
                [ 1 ] Department of General Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine Tsinghua University Beijing China
                Author notes
                [*] [* ] Correspondence

                Bin Luo, Department of General Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China.

                Email: luobin@ 123456mail.tsinghua.edu.cn

                Author information
                https://orcid.org/0000-0001-8866-1628
                https://orcid.org/0000-0002-8721-4460
                Article
                CAM44326
                10.1002/cam4.4326
                8607243
                34612593
                80bb7119-7973-4a0a-ac8f-eba5562ac6ed
                © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 September 2021
                : 02 June 2021
                : 10 September 2021
                Page count
                Figures: 7, Tables: 2, Pages: 13, Words: 6493
                Funding
                Funded by: Beijing Municipal Health System High‐level Health Technical Talent Training Program
                Award ID: 2013‐2‐032
                Categories
                Research Article
                Clinical Cancer Research
                Research Articles
                Custom metadata
                2.0
                November 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.9 mode:remove_FC converted:22.11.2021

                Oncology & Radiotherapy
                bone metastasis,breast cancer,her2,nomogram,prognosis,seer
                Oncology & Radiotherapy
                bone metastasis, breast cancer, her2, nomogram, prognosis, seer

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