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: firstname.lastname@example.org
MariottoAB, EtzioniR, HurlbertM, . Estimation of the number of women living with metastatic breast cancer in the United States. Cancer Epidemiol Biomarkers Prev 2017;26:809–815.10.1158/1055-9965.EPI-16-088928522448)| false
LobbezooDJ, van KampenRJ, VoogdAC, . Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer? Br J Cancer 2015;112:1445–1451.2588000810.1038/bjc.2015.127)| false
EdgeSB, ComptonCC. The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM. Ann Surg Oncol 2010;17:1471–1474.10.1245/s10434-010-0985-420180029)| false
ZouX, YouR, LiuH, . Establishment and validation of M1 stage subdivisions for de novo metastatic nasopharyngeal carcinoma to better predict prognosis and guide treatment. Eur J Cancer2017;77(Supplement C):117–126.
ZouX, YouR, LiuH, . Establishment and validation of M1 stage subdivisions for de novo metastatic nasopharyngeal carcinoma to better predict prognosis and guide treatment. Eur J Cancer 2017;77(Supplement C):117–126.10.1016/j.ejca.2017.02.029)| false
SoranA, OzmenV, OzbasS, . Randomized trial comparing resection of primary tumor with no surgery in stage IV breast cancer at presentation: protocol MF07-01. Ann Surg Oncol 2018;25:3141–3149.2977740410.1245/s10434-018-6494-6)| false
Surveillance, Epidemiology, and End Results Program. SEER*Stat Database: Incidence - SEER 9 Regs Research Data, Nov 2017 Sub (1973-2015) - Linked To County Attributes - Total U.S., 1969-2016 Counties, National Cancer Institute, DCCPS, Surveillance Research Program. Based on November 2017 submission. Released April 2018.
GrayRJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat1988;16:1141–1154.
RahmanZU, FryeDK, SmithTL, . Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy: a reference. Cancer1999;85:104–111.
RahmanZU, FryeDK, SmithTL, . Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy: a reference. Cancer 1999;85:104–111.10.1002/(SICI)1097-0142(19990101)85:1<104::AID-CNCR15>3.0.CO;2-R9921981)| false
YamamuraJ, KamigakiS, FujitaJ, . The difference in prognostic outcomes between De Novo stage IV and recurrent metastatic patients with hormone receptor-positive, HER2-negative breast cancer. In Vivo2018;32:353–358.
YamamuraJ, KamigakiS, FujitaJ, . The difference in prognostic outcomes between De Novo stage IV and recurrent metastatic patients with hormone receptor-positive, HER2-negative breast cancer. In Vivo 2018;32:353–358.29475920)| false
WarschkowR, GüllerU, TarantinoI, . Improved survival after primary tumor surgery in metastatic breast cancer: a propensity-adjusted, population-based SEER trend analysis. Ann Surg 2016;263:1188–1198.2694363510.1097/SLA.0000000000001302)| false
LaneWO, ThomasSM, BlitzblauRC, . Surgical resection of the primary tumor in women with de novo stage IV breast cancer: contemporary practice patterns and survival analysis. Ann Surg 2019;269:537–544.2922734610.1097/SLA.0000000000002621)| false
PetrelliF, BarniS. Surgery of primary tumors in stage IV breast cancer: an updated meta-analysis of published studies with meta-regression. Med Oncol 2012;29:3282–3290.2284329110.1007/s12032-012-0310-0)| false
BadweR, HawaldarR, NairN, . Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol 2015;16:1380–1388.10.1016/S1470-2045(15)00135-726363985)| false
RuiterkampJ, ErnstMF, van de Poll-FranseLV, . Surgical resection of the primary tumour is associated with improved survival in patients with distant metastatic breast cancer at diagnosis. Eur J Surg Oncol2009;35:1146–1151.
RuiterkampJ, ErnstMF, van de Poll-FranseLV, . Surgical resection of the primary tumour is associated with improved survival in patients with distant metastatic breast cancer at diagnosis. Eur J Surg Oncol 2009;35:1146–1151.1939818810.1016/j.ejso.2009.03.012)| false
RapitiE, VerkooijenHM, VlastosG, . Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis. J Clin Oncol 2006;24:2743–2749.1670258010.1200/JCO.2005.04.2226)| false