Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study

Jin-Hu Fan; Su Zhang; Huan Yang; Zong-Bi Yi; Qu-Chang Ouyang; Min Yan; Xiao-Jia Wang; Xi-Chun Hu; Ze-Fei Jiang; Tao Huang; Zhong-Sheng Tong; Shu-Sen Wang; Yong-Mei Yin; Hui Li; Run-Xiang Yang; Hua-Wei Yang; Yue-E Teng; Tao Sun; Li Cai; Hong-Yuan Li; Xue-Nong Ouyang; Jian-Jun He; Xin-Lan Liu; Shun-E Yang; Jia-Yu Wang; Bing-He Xu; You-Lin Qiao

doi:10.3389/fonc.2023.978985

Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study

Front Oncol. 2023 Jan 25:13:978985. doi: 10.3389/fonc.2023.978985. eCollection 2023.

Authors

Jin-Hu Fan¹, Su Zhang², Huan Yang¹, Zong-Bi Yi³, Qu-Chang Ouyang⁴, Min Yan⁵, Xiao-Jia Wang⁶, Xi-Chun Hu⁷, Ze-Fei Jiang⁸, Tao Huang⁹, Zhong-Sheng Tong¹⁰, Shu-Sen Wang¹¹, Yong-Mei Yin¹², Hui Li¹³, Run-Xiang Yang¹⁴, Hua-Wei Yang¹⁵, Yue-E Teng¹⁶, Tao Sun¹⁷, Li Cai¹⁸, Hong-Yuan Li¹⁹, Xue-Nong Ouyang²⁰, Jian-Jun He²¹, Xin-Lan Liu²², Shun-E Yang²³, Jia-Yu Wang³, Bing-He Xu³, You-Lin Qiao¹

Affiliations

¹ Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of Operations Management, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
³ Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁴ Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha, China.
⁵ Department of Breast Disease, Henan Breast Cancer Center, The affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
⁶ Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
⁷ Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁸ Department of Breast Cancer, The Fifth Medical Centre of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
⁹ Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁰ Department of Breast Oncology, Key Laboratory of Breast Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
¹¹ Department of Medical Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
¹² Department of Medical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
¹³ Department of Breast Surgery, Sichuan Province Tumor Hospital, Chengdu, Sichuan, China.
¹⁴ Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, China.
¹⁵ Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.
¹⁶ Departments of Medical Oncology and Thoracic Surgery, The First Hospital of China Medical University, Shenyang, China.
¹⁷ Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Key Laboratory of Liaoning Breast Cancer Research, Shenyang, China.
¹⁸ The 4th Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
¹⁹ Department of the Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
²⁰ Department of Medicine Oncology, 900Hospital of the Joint Logistics Team, Fuzhou, China.
²¹ Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
²² Department of oncology, General Hospital of Ningxia Medical University, Ningxia, China.
²³ Department of Breast Cancer and Lymphoma, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.

Abstract

Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC).

Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites.

Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07).

Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

Keywords: advanced breast cancer; clinical epidemiological characteristic; molecular subtype; retrospective study; site of distant metastasis.

Grants and funding

This work was supported by the Investigator initiated program of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CH-BC-045).