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

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

doi:10.3389/fonc.2022.942320

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

Front Oncol. 2022 Sep 29:12:942320. doi: 10.3389/fonc.2022.942320. eCollection 2022.

Authors

Chaofan Li¹, Mengjie Liu¹, Jia Li¹, Xixi Zhao², Yusheng Wang³, Xi Chen¹, Weiwei Wang¹, Shiyu Sun¹, Cong Feng¹, Yifan Cai¹, Fei Wu¹, Chong Du¹, Yinbin Zhang¹, Shuqun Zhang¹, Jingkun Qu¹

Affiliations

¹ Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
² Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
³ Department of Otolaryngology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Abstract

Background: Breast cancer (BC) survivors have an increased risk of developing second primary cancers (SPCs); however, it is still unclear if metastasis is a risk factor for developing SPCs. Usually, long-term cancer survivors face an increased risk of developing SPCs; however, less attention has been paid to SPCs in patients with metastatic cancer as the survival outcomes of the patients are greatly reduced.

Methods: A total of 17,077 American women diagnosed with breast cancer between 2010 and 2018 were identified from Surveillance, Epidemiology, and End Results (SEER) database and were included in the study. The clinical characteristics, standardized incidence ratio (SIR), standardized mortality ratio (SMR), and patterns of SPCs in BC patients with no metastasis, regional lymph node metastasis, and distant metastasis were investigated. Kaplan-Meier method was used to compare the prognosis of BC patients after developing SPCs with different metastatic status. XGBoost, a high-precision machine learning algorithm, was used to create a prediction model to estimate the prognosis of metastatic breast cancer (MBC) patients with SPCs.

Results: The results reveal that the SIR (1.01; 95% CI, 0.99-1.03, p>0.05) of SPCs in non-metastasis breast cancer (NMBC) patients was similar to the general population. Further, patients with regional lymph node metastasis showed an 8% increased risk of SPCs (SIR=1.08, 95%CI, 1.05-1.11, p<0.05), and patients with distant metastasis had a 26% increased risk of SPCs (SIR=1.26, 95%CI, 1.16-1.37, p<0.05). The SIR of SPCs in all patients below the age of 40 was the highest, which decreased with age. Patients with poorly differentiated cancers, large tumor size, and late N stage had an increased risk of SPCs. However, an increase in SIR of SPCs was observed in distant MBC patients, even at the early T1 (SIR=1.60, 95% CI, 1.22-1.98, p<0.05) and N1 (SIR=1.27, 95% CI, 1.10-1.44, p<0.05) stage. An increase in the SIR of SPCs was observed in patients with triple-negative BC, and the SIR of SPC increased with metastasis development in BC patients with luminal A subtype. The peak of SPCs risk occurrence was earlier in MBC patients (4-6 months and 10 months) compared to NMBC patients (12 months). The effect of metastasis on the prognosis of SPCs patients was dependent on the type of SPCs. Meanwhile, the XGBoost model was created to predict the 3-year (AUC=0.873) and 5-year survival (AUC=0.918) of SPCs in MBC patients.

Conclusions: Our study provides novel insight into the impact of metastasis on SPCs in BC patients. Metastasis could promote the second primary tumorigenesis which further increased cancer-related deaths. Therefore, more attention should be paid to the occurrence of SPCs in MBC patients.

Keywords: XGBoost algorithm; breast cancer; metastasis; second primary cancers; standardized incidence ratio; standardized mortality ratio.