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PLoS One. 2016 Feb 19;11(2):e0148597. doi: 10.1371/journal.pone.0148597. eCollection 2016.

Risk of Second Non-Breast Primary Cancer in Male and Female Breast Cancer Patients: A Population-Based Cohort Study.

Hung MH1,2,3, Liu CJ4,5, Teng CJ2,6, Hu YW1,2, Yeh CM7, Chen SC4,2, Chien SH4,2, Hung YP1,2, Shen CC8,9, Chen TJ7, Tzeng CH4,2, Liu CY1,2,10.

Author information

Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Program in Molecular Medicine, School of Life Sciences, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.
Division of Hematology and Oncology Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
Division of Oncology and Hematology, Department of Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan.
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Department of Psychiatry, Chiayi Branch, Taichung Veterans General Hospital, Chiayi, Taiwan.
Department of Information Management, National Chung-Cheng University, Chiayi, Taiwan.
Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.


Female breast cancer patients have an increased risk of developing subsequent malignant diseases, but this issue is rarely discussed in regards to male breast cancer patients. Thus, we conducted a national survey that included 100,915 female and 578 male breast cancer patients to investigate the risk of second primary malignancy (SPM). During a follow-up period that included 529,782 person-years, 3,153 cases of SPM developed. Compared with the general population, the standardized incidence ratio (SIR) of SPM in breast cancer patients was 1.51 [95% confidence interval (CI): 1.46-1.56]. The observed risk was significantly higher in male patients (SIR 2.17, 95% CI 1.70-2.73) and in patients whose age at breast cancer diagnosis was 40 years or younger (SIR 3.39, 95% CI 2.80-4.07), comparing to age-matched general population. Compared with the overall female population, the SIRs of female breast cancer patients with uterine (SIR: 2.66, 95% CI: 2.37-2.98), thyroid (SIR: 2.30, 95% CI: 2.02-2.62), and bone and soft tissue (SIR: 2.16, 95% CI: 1.56-2.91) cancers were significantly increased. Male breast cancer patients also displayed significantly higher SIRs for thyroid (SIR: 13.2, 95% CI: 1.60-47.69), skin (SIR: 8.24, 95% CI: 3.02-17.94) and head and neck (SIR: 4.41, 95% CI: 2.35-7.54) cancers. Among breast cancer patients, risk factors significantly associated with SPM included male gender, older age, chemotherapy treatment and comorbidity with liver cirrhosis. From our analysis, we concluded that the risk of SPM was significantly higher for both male and female breast cancer patients compared with the general population, suggesting that more intensive surveillance may be needed, especially in high-risk patients.

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