AUTHOR=Li Chaofan , Liu Mengjie , Li Jia , Zhao Xixi , Wang Yusheng , Chen Xi , Wang Weiwei , Sun Shiyu , Feng Cong , Cai Yifan , Wu Fei , Du Chong , Zhang Yinbin , Zhang Shuqun , Qu Jingkun 

TITLE=Relationship between metastasis and second primary cancers in women with breast cancer

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.942320

DOI=10.3389/fonc.2022.942320

ISSN=2234-943X

ABSTRACT=Background: Breast cancer (BC) survivors have an increased risk of developing a second primary cancers (SPCs), however, whether metastasis raise this risk is still unclear. Usually, long-term survivors face increased risk of SPCs, thus SPCs in metastatic patients has received less attention. 
Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, a total of 17,077 female patients diagnosed with breast cancer between 2010 and 2018 were included in this analysis. We investigated the patterns, clinical characteristics, standardized incidence ratio (SIR) and standardized mortality ratio (SMR) of SPCs in BC patients with non-metastasis, regional lymph node metastasis and distant metastasis. We also used Kaplan-Meier methods to compare the prognosis after developing SPCs in BC patients with different metastatic status. Finally, we used xgboost algorithm, a kind of high precision machine learning, to create a predictive model to estimate prognosis of metastatic breast cancer (MBC) patients with SPCs. 
Results: We found that metastasis could affect the patterns of SPCs and increase their SIR and SMR in BC patients. We also found the risk of second malignancies in BC patients was associated with age、race、T/N stage、molecular subtype and so on, however, in different metastasis status, the characteristics of the risk might be different. In MBC patients, the peak of SPCs risk occurred earlier than that in non-metastatic breast cancer (NMBC) patients. And the effect of metastasis on prognosis in SPCs patients depended on the types of SPCs. Meanwhile, we created a xgboost model to predict the 3-year (AUC=0.873) and 5-year survival (AUC=0.918) of SPCs in MBC patients. 
Conclusions: This work gave us novel insight into the role of metastasis in SPCs of BC patients, metastasis could promote the second primary tumorigenesis and cancer-related death. We need improve long-term follow-up for SPCs diagnosis, especially in distant MBC patients.