Increased risk of tuberculosis in oral cancer patients in an endemic area: a nationwide population-based study.

OBJECTIVES: We investigated the incidence of tuberculosis (TB) in patients with newly diagnosed oral cancer and analyzed the risk factors for TB development and mortality in oral cancer patients. MATERIALS AND METHODS: We used Taiwan's National Health Insurance Database to determine the incidence of TB and to analyze the risk factors for TB in patients newly diagnosed with oral cancer. From 2000 to 2011, we identified 40,327 oral cancer patients and the same number of subjects from the general population matched for sex, age, and comorbidities at a 1:1 ratio. RESULTS: Compared with the matched cohort, oral cancer patients exhibited a higher risk for TB (adjusted hazard ratio (aHR) 2.36, 95% confidence interval (CI) 2.06-2.71). Age ≥ 50 (aHR 1.90, 95% CI 1.57-2.29), being male (aHR 1.98, 95% CI 1.36-2.89), having diabetes mellitus (aHR 1.31, 95% CI 1.05-1.64), alcohol use disorder (aHR 1.42, 95% CI 1.06-1.89), human immunodeficiency virus (HIV) (aHR 8.24, 95% CI 2.05-33.14), chemotherapy (aHR 1.41, 95% CI 1.15-1.72), and radiotherapy for oral cancer (aHR 1.92, 95% CI 1.57-2.36) were identified as independent risk factors for TB in oral cancer patients. Hyperlipidemia was an independent protective factor for TB in oral cancer patients. CONCLUSION: Old age, male sex, diabetes mellitus, alcohol use disorder, and HIV were independent risk factors for TB in patients with oral cancer. CLINICAL RELEVANCE: High-risk oral cancer patients should be regularly screened for TB, especially those in endemic areas.

Second primary malignancy risk among patients with gastric cancer: a nationwide population-based study in Taiwan.

BACKGROUND: Several studies have reported an increase in second primary malignancies (SPMs) among gastric cancer patients. METHODS: Patients who were newly diagnosed with gastric cancer between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent malignancies or gastrointestinal stromal tumor were excluded. Standardized incidence ratios (SIRs) of SPMs were calculated. Risk factors for cancer development were analyzed by Cox proportional hazards models. Effects of treatments for gastric cancer were treated as time-dependent variables. RESULTS: During the 15-year study period, 47,729 gastric cancer patients were recruited. Overall, 2,110 SPMs developed during a total follow-up of 137,798 person-years. The SIR for all cancers was 1.46. The SIRs for specific follow-up periods were 1.43, 1.41, and 1.21 at >10 years, 5-10 years, and 1-5 years, respectively. After excluding SPMs that developed within 1 year, significantly higher SIRs were seen for cancers of the head and neck (1.34), esophagus (2.16), colon and rectum (1.37), bones and soft tissues (1.95), ovaries (2.89), bladder (1.47), or kidneys (1.44), as well as non-Hodgkin's lymphoma (5.56). Multivariate analysis showed that age ≥70 years [hazard ratio (HR) 1.19], being male (HR 1.37), diabetes mellitus (HR 1.30), chronic obstructive pulmonary disease (HR 1.17), and liver cirrhosis (HR 1.94) were independent risk factors. Radiotherapy (HR 1.24) and chemotherapy (HR 1.87) were independent risk factors, but surgery (HR 0.67) was not. CONCLUSIONS: Patients with gastric cancer are at increased risk of developing SPM. Close surveillance of patients with risk factors over a longer period should be considered.

Frequency of surveillance computed tomography in non-Hodgkin lymphoma and the risk of secondary primary malignancies: A nationwide population-based study.

With increasing usage of computed tomography (CT) for lymphoma patients receiving curative-intent treatment, development of secondary primary malignancy (SPM) related to radiation from CT scans becomes an emerging issue in these long-term survivors. We conducted a nationwide population-based study analyzing non-Hodgkin lymphoma (NHL) patients receiving curative-intent treatment between January 1997 and December 2010. Patients were divided into two populations by the medium number of CT performed. The cumulative incidence of SPM in these two groups was compared using the Kaplan-Meier method. Propensity score matching was applied to eliminate potential confounders. Group stratification and multivariate analyses calculated by Cox proportional hazard models using competing risk analyses adjusted for mortality were performed to identify independent predictors for SPM. Patients receiving >8 CT scans had a significantly greater risk for developing SPM (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.61-3.13; p < 0.001) than those with ≤8 scans and this difference remained significant even after correction with propensity score matching. Among the 180 SPM identified, those receiving more CT scans had significantly higher SPM incidence in cancers of the breast (HR 11.22), stomach (HR 5.22) and liver and biliary tract (HR 2.18) in comparison to those with less exposure. The risk of SPM was estimated to increase 3% per one more CT scan performed. Our study demonstrated that after curative-intent treatment, patients with NHL receiving more frequent surveillance CT scans would have an increased risk of SPM.

Risk and impact of tuberculosis in patients with chronic myeloid leukemia: a nationwide population-based study in Taiwan.

The relationship between chronic myeloid leukemia (CML) and tuberculosis (TB) has not been determined. We conducted a national survey including 1,082 CML patients identified from the Taiwan National Health Insurance database covering a period between 1998 and 2011; the matched non-exposed cohort included 10,820 subjects without CML that were matched for age, sex and comorbidities. The impact of TB was measured by the overall mortality, and the risk factors were identified by a multivariate Cox proportional hazards model. We found the risk of TB was higher in the CML cohort, with an adjusted hazard ratio (aHR) of 3.76 (p = 0.001) for both pulmonary (aHR 3.23, p < 0.001) and extrapulmonary (aHR 9.77, p = 0.001) TB. Specific risk factors were: aged ≥ 60 (aHR 3.24, p = 0.022), being male (aHR 13.49, p = 0.012), receiving stem cell transplantation (aHR 10.50, p = 0.001) and interferon-α therapy (aHR 3.34, p = 0.011). CML patients with TB had a higher mortality rate than those without (aHR 2.04, p = 0.043). We conclude that the incidence of TB is significantly higher in CML patients of male sex, aged ≥ 60, having received either stem cell transplantation or interferon-α treatment. Careful screening strategies for TB should be considered for CML patients with high risk of the infection.

Association of surgeon volume and hospital volume with the outcome of patients receiving definitive surgery for colorectal cancer: A nationwide population-based study.

BACKGROUND: Patients with colorectal cancer (CRC) who undergo cancer surgeries with higher-volume providers may have better outcomes. The current debate focuses on whether it is hospital volume or surgeon volume that matters more. METHODS: The authors conducted a nationwide population-based study in Taiwan that enrolled all patients who underwent definitive surgery for newly diagnosed CRC between 2005 and 2011. All patients were divided into 4 quartiles according to hospital and surgeon volume. The main outcome was the 5-year mortality rate, which was analyzed using a frailty model for Cox regression. The authors also conducted fixed and random effects multivariate regression models to examine short-term outcomes and resource use, including operative mortality, hospital stay, emergency department visits within 30 days, and medical expenses. Analyses were adjusted for patient and provider characteristics. RESULTS: A total of 61,728 patients with CRC were included in the current study. The 5-year mortality rates were 38.7%, 32.8%, 32.0%, and 29.1% in descending order of hospital volume quartiles and were 41.4%, 34.1%, 29.8%, and 27.4% in descending order of surgeon volume quartiles. After adjustment for the individual and provider characteristics, surgeon volume, but not hospital volume, remained a significantly predictive factor of death (P<.001). In addition, those patients with CRC who underwent definitive surgeries performed by higher-volume surgeons had a relatively lower risk of operative mortality, shorter hospital length of stay, and lower medical expenses. CONCLUSIONS: Patients with CRC who underwent definitive surgery performed by higher-volume providers were found to have better outcomes. Surgeon volume may play a more important role than hospital volume. Cancer 2015;121:2782-2790. © 2015 American Cancer Society.

Anxiety and depressive disorders among patients with esophageal cancer in Taiwan: a nationwide population-based study.

BACKGROUND: The comorbidity of depression with anxiety disorders is associated with poorer treatment outcomes, worse quality of life, poorer adherence to treatment, and greater suicide risk in cancer patients. OBJECTIVE: To assess the risk of comorbid anxiety and depressive disorders after the diagnosis of esophageal cancer compared with a matched cohort by using the Taiwan National Health Insurance Research Database (NHIRD). METHODS: We conducted a retrospective study of 28,454 patients (14,227 patients with esophageal cancer and 14,227 matched patients) who were selected from the NHIRD. Patients were observed for a maximum of 12 years to determine the incidence of new-onset anxiety and depressive disorders for which antidepressants had been prescribed. A Cox regression analysis was performed to identify the risk factors associated with anxiety and depressive disorders in esophageal cancer patients. RESULTS: The cumulative incidence of anxiety and depressive disorders in the esophageal cancer patients was significantly higher than that in the matched cohort (P < .001). The adjusted hazard ratio (HR) was 2.24 (95 % confidence interval, CI = 1.95-2.56, P < .001) in the esophageal cancer cohort compared with the matched cohort. Independent risk factors for developing anxiety and depressive disorders among the patients with esophageal cancer included cirrhosis, cerebrovascular disease, and surgical treatment. CONCLUSION: Esophageal cancer may be a prominent risk factor for anxiety and depressive disorders. Based on our data, we suggest that attention should be focused on esophageal cancer patients with comorbid cirrhosis and cerebrovascular disease and those who have received surgical interventions.

Cancer risk among patients with coal workers' pneumoconiosis in Taiwan: a nationwide population-based study.

This study is aimed to evaluate the cancer risk among patients with coal workers' pneumoconiosis (CWP) using a nationwide population-based dataset. Patients without previous cancer who had been diagnosed with CWP and followed-up for more than 1 year between 1997 and 2006 were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of cancers in CWP patients were calculated and compared to the cancer incidence in the general population. Risk factors for cancer development were also analyzed. After a median follow-up of 9.68 years, 954 cancers developed among 8,051 recruited CWP patients, with a follow-up of 69,398 person-years. The SIR for all cancers was 1.12 [95% confidence interval (CI) 1.04-1.18]. Males older than 80 years had a SIR of 1.27 (95% CI: 1.06-1.51). The SIRs of esophageal (1.76, 95% CI: 1.24-2.44), gastric (1.42, 95% CI: 1.13-1.76), liver and biliary tract (1.18, 95% CI: 1.01-1.37) and lung and mediastinal (1.45, 95% CI: 1.26-1.66) cancers were significantly higher in the CWP group than in the general population. Multivariate analysis showed that age ≥ 60 years [hazard ratio (HR) 1.70, 95% CI: 1.41-2.05), male gender (HR = 1.79, 95% CI: 1.44-2.23) and liver cirrhosis (HR = 3.99, 95% CI: 2.89-5.51) were significant predictors of cancer development in patients with CWP. We concluded that patients with CWP, especially elderly males, were at increased risk of cancer. Age, male gender and liver cirrhosis were independent risk factors for cancer development.

Risk of ischemic stroke in patients with ovarian cancer: a nationwide population-based study.

BACKGROUND: Cancer patients are at risk of thromboembolism. However, studies investigating the relationship between ovarian cancer and ischemic stroke are lacking. The objectives of this study were to assess the association between ovarian cancer and ischemic stroke, and to determine the predictive risk factors. METHODS: Ovarian cancer patients aged 20 years and older without antecedent cerebrovascular events and who were followed up for more than 1 year between 1 January 2003 and 31 December 2011 were recruited from the Taiwan National Health Insurance database. Hazard ratios (HRs) of stroke risk for ovarian cancer patients compared with an age- and comorbidity-matched cohort were calculated by Cox proportional regression analysis. The difference in cumulative ischemic stroke incidence between ovarian cancer patients and the matched cohort was analyzed with the Kaplan-Meier method and tested with the log-rank test. RESULTS: Each cohort (ovarian cancer and matched cohort) consisted of 8,810 individuals, with a median age of 49 years. After a median follow-up of 2.68 and 3.85 years, respectively, the ischemic stroke incidence was 1.38-fold higher in the ovarian cancer cohort than in the comparison cohort (9.4 versus 6.8 per 1,000 person-years), with an age- and comorbidity-adjusted HR of 1.49 (P <0.001). The ischemic stroke risk imposed by ovarian cancer was more prominent in patients under 50 years old (HR 2.28; P <0.001) compared with patients 50 years and older (HR 1.33; P = 0.005). Significant risk factors predicting stroke development were age 50 years and older (HR 2.21; P <0.001), hypertension (HR 1.84; P <0.001), diabetes mellitus (HR 1.71; P <0.001), and treatment with chemotherapy (HR 1.45; P = 0.017), especially platinum-based regimens. CONCLUSIONS: Ovarian cancer patients were at an increased risk of developing ischemic stroke. Age, hypertension, diabetes, and chemotherapy treatment were independent risk factors.

The impact of surgical volume on outcomes in newly diagnosed colorectal cancer patients receiving definitive surgeries.

Colorectal cancer (CRC) patients who receive cancer surgeries from higher-volume providers may have better outcomes. However, the definitions of surgical volume may affect the results. We aim to analyze the effects of different definitions of surgical volume on patient outcomes. We conducted a nationwide population-based study in Taiwan that enrolled all patients who underwent definitive surgery for newly diagnosed CRC. We used three common definitions of surgical volume: total volume means the total surgical number conducted by the same provider during the study period; cumulative volume was calculated as the number of operations the surgeon performed before the index procedure; annual volume was calculated as the number of times the surgeon had been responsible for surgery during the index year. In this study, we included 100,009 newly diagnosed CRC patients, including 55.8% males, of median age 66 years at diagnosis (range 20-105 years). After adjustment for the patient and provider characteristics, we found that CRC patients receiving definitive surgery by higher-volume providers had better outcomes, especially where surgeon volume may play a more important role than hospital volume. The cumulative volume could predict the 5-year mortality of the study cohort better than the total and annual volume.

Duloxetine improves oxaliplatin-induced neuropathy in patients with colorectal cancer: an open-label pilot study.

BACKGROUND: This open-label pilot study is aimed to evaluate the efficacy and tolerability of the antidepressant duloxetine, which is effective for diabetic neuropathic pain, in the treatment of chronic oxaliplatin-induced peripheral neuropathy (OIPN). METHODS: We enrolled a total of 39 patients with stage III or IV colorectal cancer with chronic OIPN. They were treated with duloxetine by increasing the dose from 30 mg/day to 60 mg/day. Patients' pain intensity was rated at baseline and 12 weeks after duloxetine administration. The severity of neuropathic pain was evaluated using the visual analog scale (VAS) score and the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3 (NCI-CTCAE v3.0). RESULTS: Nine patients (23.1%) discontinued duloxetine before the end of treatment because of adverse events. Of the remaining 30 patients, 19 patients (63.3%) had a VAS score improvement. Among them, nine (47.4%) showed a simultaneous grade improvement, and the other 10 patients (52.6%) had a stable grade according to NCI-CTCAE v3.0. Treatment with duloxetine did not impair renal or liver function and did not interfere with chemotherapy. CONCLUSIONS: Duloxetine is feasible in treating chronic OIPN with tolerable toxicity at a daily dose of 60 mg/day.

Sudden-onset pancytopenia with intracranial hemorrhage after oxaliplatin treatment: a case report and literature review.

Oxaliplatin is a third-generation platinum compound and has been widely employed in the treatment of colorectal cancer. Despite its good efficacy, it is reported to induce immune-mediated cytopenia. We report the case of a 78-year-old male patient who experienced acute pancytopenia along with coagulopathy and intracranial hemorrhage after his 17th course of oxaliplatin. This condition appeared immediately after completion of oxaliplatin infusion, and was persistent despite aggressive transfusion and treatment with granulocyte colony-stimulating factor. The patient died 72 h after the administration of oxaliplatin. The only preceding symptom was chills 30 min after initiation of oxaliplatin, although steroid was given as premedication. We review the literature describing oxaliplatin-induced cytopenia, and discuss the manifestation, immune mechanism and treatment of this condition. We conclude that any symptoms that occur during infusion of oxaliplatin should not be overlooked but should be taken seriously as they may represent 'a little spark that kindles a great fire', and that steroids may provide an effective treatment for oxaliplatin-induced cytopenia. However, a major complication in our patient may still happen. Further studies for the mechanism and the predictive markers of oxaliplatin-induced cytopenia are worthy.

High early mortality rate in elderly patients with multiple myeloma receiving a vincristine-doxorubicin-dexamethasone regimen.

Treatment-related mortality (TRM) is not uncommon in patients after the first course of vincristine-doxorubicin-dexamethasone (VAD) chemotherapy,but quite rare after melphalan-prednisolone (MP). This motivated us to compare the rates of TRM after the first course of VAD with those after the first course of MP. We retrospectively assessed survival and TRM in 179 patients treated for multiple myeloma with either MP or VAD. Survival was similar in two groups (P 50.463 in log-rank test). However, TRM was significantly higher inpatients after the first course of VAD (11 in 100 patients, 11.0%) than that after the first course of MP (1 in 79, 1.3%; P 5 0.010). Poor performance status (P 5 0.004) and advanced age (P 5 0.009) before treatment were independent significant factors associated with TRM after the first course of induction therapy. Pyogenic infection was the major cause of TRM after VAD (9 in 11, 81.8%). We concluded that VAD should be cautiously used as induction therapy in multiple myeloma patients, especially in elderly and/or those with poor performance status.

Liver Transplantation After Downstagings of Ruptured Advanced Hepatocellular Carcinoma in Cirrhotic Liver: Is It Advisable? A Case Report.

Spontaneous rupture of hepatocellular carcinoma (HCC), defined as T4 in TNM stage by the American Joint Committee on Cancer (eighth edition), is a serious life-threatening complication. Effective treatment remains challenging because of a high 1-month mortality, a short median survival, and the potential of peritoneal metastasis. We reported on a case that received a living related donor liver transplantation (LDLT) after successful consecutive downstaging therapies. A 63-year-old man with alcohol-related liver cirrhosis and multiple HCC developed spontaneous rupture and hemoperitoneum. He received 3 sessions of transcatheter hepatic arterial chemoembolization and target therapy with sorafenib. Computed tomography scans and magnetic resonance imaging after 11 months of treatment showed that the patient's HCCs fulfilled the Milan criteria and the University of California San Francisco criteria prior to LDLT. The perioperative course was rather smooth. After discharge, interval follow-up computed tomography studies of chest and liver and a whole-body bone scan showed no tumor recurrence or metastasis up to 20 months post-operation. Successful downstaging therapies of ruptured HCC to fulfill Milan criteria to receive liver transplantation is advisable in highly selected patients.

Cancer Risk in Patients With Empyema: A Nationwide Population-Based Study.

This study aimed to evaluate cancer risk and possible risk factors in patients diagnosed with empyema. A total of 31,636 patients with newly diagnosed empyema between January 1, 1999 and December 31, 2010 were included in this study. Standardized incidence ratios (SIRs) were calculated to compare the cancer incidence in these empyema patients to that in the general population. Adjusted hazard ratios were also calculated to investigate whether characteristics increased cancer risk. During the 12-year study period, 2,654 cancers occurred in 31,636 patients with empyema, yielding an SIR of 2.67 (95% confidence interval [CI] 2.57-2.78). We excluded cancer that occurred within 1 year to avoid surveillance bias. The cancer risk remained significantly increased (SIR 1.50, 95% CI 1.41-1.58). Specifically, patients with empyema had higher SIR of cancers of the head and neck (1.50, 95% CI 1.41-1.58), esophagus (2.56, 95% CI 1.92-3.33), stomach (1.49, 95% CI 1.16-1.89), liver and biliary tract (2.18, 95% CI 1.93-2.45), and lung and mediastinum (1.62, 95% CI 1.39-1.86). Age ≥ 60, male sex, diabetes mellitus, and liver cirrhosis were independent risk factors for cancer development. Our study demonstrates an increased incidence of cancer development in patients with empyema, and patients' age ≥ 60, men, and those with diabetes mellitus and liver cirrhosis showed a higher incidence of developing cancer compared to the general population. The association between such kind of infection and secondary malignancy may be elucidated by further study.

Correction: Secondary Solid Organ Neoplasm in Patients with Acute Lymphoblastic Leukemia: A Nationwide Population-Based Study in Taiwan.

[This corrects the article DOI: 10.1371/journal.pone.0152909.].

Secondary Solid Organ Neoplasm in Patients with Acute Lymphoblastic Leukemia: A Nationwide Population-Based Study in Taiwan.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is more common in children than in adults. Secondary neoplasms (SNs) in childhood ALL have been widely reported. However, only one study has demonstrated SNs in adult ALL. Because of the poorer survival of adult ALL, the incidence might be underestimated. OBJECTIVE: To evaluate the incidence and risk factors of secondary solid organ neoplasms among adult and child ALL patients. METHODS: Newly diagnosed ALL patients between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent or combined malignancies were excluded. Standardized incidence ratios (SIRs) were analyzed to compare the risk of our cohort to general population in the same age, sex and calendar year. Risk factors for SN development were analyzed by Cox proportional hazards models. Effects of treatments were treated as time-dependent variables. RESULTS: The 15-year cumulative incidence of SN was 1.9% and 8.4% in 1,381 child and 2,154 adult ALL patients, respectively. The SIR was significantly increased in child ALL (SIR 6.06), but not in adult ALL (SIR 1.16). The SIRs of follow-up periods were 5.14, 2.24, .87 and .71 at ≥ 10 years, 5-10 years, 1-5 years and 0-1, respectively. Overall, 15 SNs developed, and CNS tumors (SIR 11.56) were the most common type. Multivariate analysis showed that age ≥ 20 years (hazard ratio [HR] 5.04), end-stage renal disease (HR 18.98) and cranial irradiation (HR 8.12) were independent risk factors for cancer development. CONCLUSIONS: When compared with the general population, child ALL shows a increased risk of developing SNs. CNS tumors are the most common type, and cranial irradiation is an independent risk factor. With longer follow-up, the risk of SNs increases. Hence, physicians need to pay more attention on the risk of developing SNs in long-term ALL survivors with risk factors.

Use of Radioactive Iodine for Thyroid Cancer and Risk of Second Primary Malignancy: A Nationwide Population-Based Study.

BACKGROUND: Radioactive iodine (RAI) is widely used for the treatment of thyroid cancers. However, information on associations between RAI dose and second primary malignancy (SPM) is lacking. METHODS: Patients without antecedent cancer age 20 years or older and newly diagnosed with thyroid cancer were recruited from the Taiwan National Health Insurance database between 1997 and 2010. Standardized incidence ratios (SIRs) for the cancers were calculated to compare the incidence of thyroid cancer with the general population. The association between RAI dosage and cancer development was estimated using time-dependent Cox regression analysis. All statistical tests were two-sided. RESULTS: A total of 692 cases of SPM were identified among 20 235 patients with thyroid cancer. Regarding the latter, 79.7% of the patients were women, the median age was 46 years, and the follow-up period included 134 178 person-years. The SIR for any SPM was 1.41 (95% confidence interval [CI] = 1.31 to 1.52). A statistically significantly higher SIR was observed in leukemia (2.74), non-Hodgkin's lymphoma (2.38), prostate (2.30), lung and mediastinum (1.93), pancreas (1.83), kidney (1.81), breast (1.48), and colon-rectum (1.31) cancers. Cumulative RAI dose (per 30 mCi increase) conferred a strong risk for SPM (adjusted hazard ratio [aHR] = 1.01, 95% CI = 1.01 to 1.02, P < .001) and leukemia (aHR = 1.03, 95% CI = 1.02 to 1.04, P < .001) occurrences. A cumulative RAI dose greater than 150 mCi possessed a statistically significant risk for all cancer combined (aHR = 1.30) and leukemia (aHR = 6.03). CONCLUSIONS: An increased risk of SPM was observed for thyroid cancer patients, especially with cumulative RAI doses over 150 mCi.

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

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.