Vol.:(0123456789) 1 3 Clinical & Experimental Metastasis https://doi.org/10.1007/s10585-017-9871-9 RESEARCH PAPER De novo metastasis in breast cancer: occurrence and overall survival stratifed by molecular subtype David J. Press 1  · Megan E. Miller 2  · Erik Liederbach 3  · Katherine Yao 3  · Dezheng Huo 1 Received: 30 July 2017 / Accepted: 20 December 2017 © Springer Science+Business Media B.V., part of Springer Nature 2017 Abstract Breast cancer molecular subtypes, categorized jointly by hormone receptors (HR) and human epidermal growth factor-2 (HER2), are utilized to guide systemic therapy. We hypothesized distinct patterns of de novo metastasis and overall survival by molecular subtype using a retrospective cohort of 399,772 women in the National Cancer Database diagnosed with frst primary invasive breast cancer between 2010 and 2014, of whom 13,924 were diagnosed with de novo metastasis from 2010 to 2013 and had follow up data. The relationship of molecular subtype with patient and tumor characteristics, including site of de novo metastasis, were examined using Chi-squared tests. Kaplan–Meier and Cox proportional hazards analyses were used to examine overall survival by molecular subtype. Bone was the most frequent de novo metastatic site for all molecular subtypes. Compared to HR+/HER2−, patients with HR−/HER2+ experienced 4.5, 3.0, and 6.0 times the de novo brain, lung, and liver metastasis respectively. In survival analyses of women diagnosed with de novo metastasis, the mortality risk relative to HR+/HER2− was twice as high for triple-negative (hazard ratio = 2.02, 95% CI 1.89–2.16) and modestly lower for HR+/HER2+ (hazard ratio = 0.83, 95% CI 0.78–0.88). The median survival diference between metastatic patients with and without chemotherapy was 28.6 months in HR+/HER2+ and 28.2 months in HR−/HER2+, but only 10.9 months in triple-negative and 5.2 months in HR+/HER2−. In conclusion, despite unfavorable patterns of de novo metastasis, HER2+ breast cancers had relatively better survival in recent years, probably due to treatment diferences. Utilizing molecular subtype and site of de novo metastasis may predict prognosis and guide treatment. Keywords Breast cancer · Subtypes · Metastasis · Survival · Epidemiology Abbreviations AJCC American Joint Committee on Cancer CoC Commission on Cancer CIs Confdence intervals ER Estrogen receptor HR Hormone receptor HER2 Human epidermal growth factor receptor 2-neu ICD-O-3 International Classifcation of Diseases for Oncology-Third edition NCDB National Cancer Database NH Non-Hispanic OS Overall survival PR Progesterone receptor Introduction Breast cancer survival is strongly stage-dependent—5-year relative survival exceeds 95% for patients with localized tumors, but drops below 30% for those with distant metas- tasis [1]. Recently, breast cancer mortality has witnessed a temporal decline, yet breast cancer remains the second most common cause of female cancer death in the US, with an estimated 40,610 female deaths in 2017 [2, 3]. Interestingly, incidence of metastatic breast cancer has remained fairly stable over the past several decades in the United States (US) [4]. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10585-017-9871-9) contains supplementary material, which is available to authorized users. * Dezheng Huo dhuo@health.bsd.uchicago.edu 1 Department of Public Health Sciences, The University of Chicago, 5841 South Maryland Avenue, MC 2000, Chicago, IL 60637, USA 2 Department of Surgery, Case Western Reserve University Hospitals, Cleveland, OH, USA 3 Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA