Subdivision of M1 Stage for De Novo Metastatic Breast Cancer to Better Predict Prognosis and Response to Primary Tumor Surgery

Authors: Caijin Lin MMed 1 , Jiayi Wu MD 1 , Shuning Ding MMed 1 , Chihwan Goh MMed 1 , Lisa Andriani MMed 1 , Shuangshuang Lu MD 1 , Kunwei Shen MD, PhD 1 and Li Zhu MD, PhD 1
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  • 1 Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China.
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Background: Patients with de novo metastatic breast cancer (MBC) constitute a heterogeneous group with different clinicopathologic characteristics and survival outcomes. Despite controversy regarding its prognostic value, primary tumor surgery may improve survival for selected patients. Patients and Methods: Patients with de novo MBC were identified using the SEER database and were then divided randomly into training and validation sets. A Fine-Gray competing risks model was developed to identify the variables associated with increased cancer-specific mortality in the training set. The M1 subdivision system was established based on the independent prognostic factors. Cumulative incidence curves were estimated and compared using Gray’s test. Results: Involvement of brain or liver and number of metastatic sites were identified as independent prognostic factors in multivariate analysis. The M1 category was subdivided into 3 subcategories: M1a, single site involvement except brain and liver; M1b, liver involvement only, or multiple site involvement except brain and liver; and M1c, brain involvement regardless of number of metastatic sites, or liver and other sites involvement except brain (M1b vs M1a: subdistribution hazard ratio [SHR], 1.48; 95% CI, 1.29–1.68; M1c vs M1a: SHR, 2.45; 95% CI, 2.18–2.75). Patients with the M1a subtype benefited most from primary tumor surgery in the adjusted competing risks model (M1a: SHR, 0.57; 95% CI, 0.48–0.67, M1b: SHR, 0.62; 95% CI, 0.47–0.83, and M1c: SHR, 0.59; 95% CI, 0.44–0.80), whereas benefits conferred by treatment with chemotherapy alone increased with the upstaging of metastatic disease (M1a: SHR, 0.72; 95% CI, 0.62–0.83, M1b: SHR, 0.54; 95% CI, 0.44–0.68, and M1c: SHR, 0.53; 95% CI, 0.45–0.61). Conclusions: Subdivision of M1 stage facilitates prognosis prediction and treatment planning for patients with de novo MBC. Treatment offered should be decided in a coordinated multidisciplinary setting. Primary tumor surgery may play an important role in the management of selected patients.

Submitted November 3, 2018; accepted for publication June 18, 2019.

Author contributions: Study concept and design: Lin, Wu, Zhu. Data acquisition: Lin, Ding, Goh. Data analysis and interpretation: Lin, Wu, Ding, Andriani, Lu, Shen. Manuscript preparation: All authors. Final approval: Zhu.

Disclosures: The authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Li Zhu, MD, PhD, Comprehensive Breast Health Center, Ruijin Hospital, 197 Ruijin Er Road, Huangpu District, Shanghai 200025, China. Email: zhuli8@yeah.net

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