Risk of second primary cancer among patients with head and neck cancers: A pooled analysis of 13 cancer registries

The objective of the study was to assess the risk of second primary cancers (SPCs) following a primary head and neck cancer (oral cavity, pharynx and larynx) and the risk of head and neck cancer as a SPC. The present investigation is a multicenter study from 13 population-based cancer registries. The study population involved 99,257 patients with a first primary head and neck cancer and contributed 489,855 person-years of follow-up. To assess the excess risk of SPCs following head and neck cancers, we calculated standardized incidence ratios (SIRs) by dividing the observed numbers of SPCs by the expected number of cancers calculated from accumulated person-years and the age-, sex- and calendar period-specific first primary cancer incidence rates in each of the cancer registries. During the observation period, there were 10,826 cases of SPCs after head and neck cancer. For all cancer sites combined, the SIR of SPCs was 1.86 (95% CI = 1.83-1.90) and the 20-year cumulative risk was 36%. Lung cancer contributed to the highest proportion of the SPCs with a 20-year cumulative risk of 13%. Excess second head and neck cancer risk was observed 10 years after diagnosis with lymphohaematopoietic cancers. The most common SPC following a first primary head and neck cancer was lung cancer. However, the highest excess of SPCs was in the head and neck region. These patterns were consistent with the notion that the pattern of cancer in survivors of head and neck cancer is dominated by the effect of tobacco smoking and alcohol drinking.     

Incidence of Smoking-Related Second Primary Cancers After Lung Cancer in Germany: An Analysis of Nationwide Cancer Registry Data

IntroductionApproximately 80% of lung cancer cases in Germany are attributable to smoking. Patients with a lung cancer diagnosis may remain at increased risk of developing smoking-related second primary cancers (SPCs).MethodsAnonymous data from 11 population-based cancer registries covering approximately 50% of the German population were pooled for the analysis. Included patients were diagnosed with having an index lung cancer between 2002 and 2013, aged 30 to 99 years old at diagnosis, and survived for at least 6 months. We calculated standardized incidence ratios (SIRs)—stratified by age, sex, region, and period—comparing the incidence of smoking-related and other SPCs to the general population.ResultsOf the 135,589 lung cancer survivors (68.2% male; mean follow-up 30.8 mo) analyzed, 5298 developed an SPC. In males, the risk was particularly high for SPCs of the larynx (SIR = 3.70, 95% confidence interval [CI]: 3.14–4.34), pharynx (3.17, 2.61–3.81), and oral cavity (2.86, 2.38–3.41). For females, SIRs were notably elevated for the esophagus (4.66, 3.15–6.66), oral cavity (3.14, 2.03–4.63), and urinary tract (2.68, 2.04–3.45). When combining all smoking-related cancer sites, SIR was 1.41 in males (95% CI: 1.36–1.47) and 1.81 in females (95% CI: 1.68–1.94). We observed that males had a 1.46-fold (95% CI: 1.37–1.56) and females a 1.33-fold (95% CI: 1.20–1.47) increased risk for smoking-related compared with other cancers.ConclusionsPatients with primary lung cancer were at increased risk for developing a smoking-related SPC. Therefore, the advantages of increased patient surveillance and the benefits of smoking cessation strategies should be considered.     

Incidence of second primary cancers among survivors of childhood cancer: A population-based study,Osaka, Japan, 1975–2015

Second primary cancer (SPC) is one of the most life-threatening late effects of childhood cancers. We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan. Data were obtained from the population-based Osaka Cancer Registry. Individuals diagnosed with cancer at age 0–14 years during 1975–2014 and survived 2 months or longer were followed through December 2015. The risk of developing SPC was assessed with standardized incidence ratio (SIR), excess absolute risk (EAR, per 100,000 person-years), and cumulative incidence. Multivariable Poisson regression analysis was carried out to assess relative risks of SPC by treatment method. Survival analysis was undertaken using the Kaplan–Meier method. Of 7229 childhood cancer survivors, 101 (1.4%) developed SPC after a median of 11.6 years. Overall SIR was 5.0, which corresponded with 84.3 EAR. The cumulative incidence was 0.9%, 2.1%, and 3.4% at 10, 20, and 30 years, respectively. Among all SPCs, the type that contributed most to the overall burden was cancers in the central nervous system (EAR = 28.0) followed by digestive system (EAR = 15.1), thyroid (EAR = 8.3), and bones and joints (EAR = 7.8); median latency ranged from 2.0 years (lymphomas) to 26.6 years (skin cancers). Patients treated with radiotherapy alone were at a 2.58-fold increased risk of developing SPC compared to those who received neither chemotherapy nor radiotherapy. Among patients who developed SPCs, 5-year and 10-year survival probabilities after SPC diagnosis were 61.7% and 52.0%, respectively. Risk-based long-term follow-up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.     

Second primary cancers in breast cancer patients in Slovenia

Data from the Cancer Registry of Slovenia were used in a cohort studyto determine whether the incidence of second primary cancers in patients withfirst primary breast cancer differs from the incidence expected in thegeneral population. Special interest was given to long-term survivors. Theexpected numbers of second primary cancers were calculated by multiplying thenumber of appropriate person-years at risk by the corresponding age-andcalendar-period-specific cancer incidence rates for women in Slovenia. Therisk of a second primary cancer was expressed as the standardized incidenceratio (SIR). Of the 8,917 patients newly diagnosed in the period 1961-85 andfollowed-up to the end of 1994, 547 (6.2 percent) developed second primarycancers, whereas 410 (4.7 percent) were expected (SIR = 1.3, 95 percentconfidence interval [CI] = 1.2-1.4). The risk was higher among youngerpatients. In long-term survivors, the risk was increased significantly forsecond primary cancer of th e breast (SIR = 1.4, CI = 1.1-1.7), lung cancer(SIR = 1.6, CI = 1.1-2.3), melanoma (SIR = 2.7, CI = 1.5-4.4) andnon-melanoma skin cancers (SIR = 2.0, CI = 1.6-2.4), corpus uteri cancer (SIR= 1.6, CI = 1.2-2.1), ovarian cancer (SIR = 2.3, CI = 1.7-3.0), and thyroidcancer (SIR = 2.5, CI = 1.2-4.6). Our results confirm the findings of severalcohort studies carried out in Europe, the United States, and Japan,indicating that breast cancer patients should be monitored carefully for theoccurrence of second primary cancers.     

Increased risk of second malignancies after in situ breast carcinoma in a population-based registry

Among 1276 primary breast carcinoma in situ (BCIS) patients diagnosed in 1972-2002 in the Southern Netherlands, 11% developed a second cancer. Breast carcinoma in situ patients exhibited a two-fold increased risk of second cancer (standardised incidence ratios (SIR): 2.1, 95% confidence interval (CI): 1.7-2.5). The risk was highest for a second breast cancer (SIR: 3.4, 95% CI: 2.6-4.3; AER: 66 patients per 10,000 per year) followed by skin cancer (SIR: 1.7, 95% CI: 1.1-2.6; AER: 17 patients per 10,000 per year). The increased risk of second breast cancer was similar for the ipsilateral (SIR: 1.9, 95% CI: 1.3-2.7) and contralateral (SIR: 2.0, 95% CI: 1.4-2.8) breast. Risk of second cancer was independent of age at diagnosis, type of initial therapy, histologic type of BCIS and period of diagnosis. Standardised incidence ratios of second cancer after BCIS (SIR: 2.3, 95% CI: 1.8-2.8) resembled that after invasive breast cancer (SIR: 2.2, 95% CI: 2.1-2.4). Surveillance should be directed towards second (ipsi- and contra-lateral) breast cancer.     

Joint and independent effect of alcohol and tobacco use on the risk of subsequent cancer incidence among cancer survivors: A cohort study using cancer registries

Drinking alcohol and smoking tobacco are major modifiable risk factors for cancer. However, little is known about whether these modifiable factors of cancer survivors are associated with subsequent primary cancer (SPC) incidence, regardless of the first cancer sites. 27,762 eligible cancer survivors diagnosed between 1985 and 2007 were investigated for SPC until the end of 2008, using hospital‐based and population‐based cancer registries. The association between drinking, smoking and combined drinking and smoking (interaction) at the time of the first cancer diagnosis and incidence of SPCs (i.e., all SPCs, alcohol‐related, smoking‐related and specific SPCs) was estimated by Poisson regression. Compared with never‐drinker/never‐smoker, the categories ever‐drinker/ever‐smoker, current‐drinker/current‐smoker and heavy‐drinker/heavy‐smoker had 43–108%, 51–126% and 167–299% higher risk for all, alcohol‐related and tobacco‐related SPCs, respectively. The interaction of drinking and smoking had significantly high incidence rate ratios (IRRs) for SPCs among ever‐drinker/ever‐smoker and current‐drinker/current‐smoker, although ever drinking did not show a significant risk. Ever‐drinker/ever‐smoker had also significantly higher IRRs for esophageal and lung SPCs than never‐drinker/never‐smoker. Among comprehensive cancer survivors, ever and current drinkers only had a SPC risk when combined with smoking, while ever and current smokers had a SPC risk regardless of drinking status. Heavy drinking and heavy smoking were considered to be independent additive SPC risk factors. To reduce SPC incidence, it may be necessary (i) to reduce or stop alcohol use, (ii) to stop tobacco smoking and (iii) dual users, especially heavy users, should be treated as a high‐risk population for behavioral‐change intervention.     

Tobacco smoking and the risk of subsequent primary cancer among cancer survivors: a retrospective cohort study

BackgroundSmoking is a well-known risk factor for cancer; however, there is little evidence as to whether the smoking status of cancer survivors has any risk for subsequent primary cancer (SPC) incidence, regardless of the first cancer sites.Patients and methodsIn total, 29 795 eligible patients with a first cancer between 1985 and 2004 were examined for SPC until the end of 2006, using a record linkage between hospital-based and population-based cancer registries. The association between smoking at the time of the first cancer diagnosis and three SPC groups (i.e. specific SPC, smoking-related SPCs, and all SPCs) was calculated by Poisson regression.ResultsEver smokers had 59% and 102% higher risk for all SPCs and smoking-related SPCs, respectively, than never smokers. Cancer survivors who had recently stopped smoking had 18% and 26% less risk, respectively, for these SPCs than those who smoked at the diagnosis. We also found that, compared with those who had never smoked, cancer survivors who had ever smoked had a significantly elevated risk of oral/pharyngeal, esophageal, stomach, lung, and hematological SPCs, regardless of the first cancer sites.ConclusionsThese findings indicate that smoking increases not only the first cancer but also a second or SPC. Moreover, the results from recent quitters versus current smokers suggest that smoking cessation may decrease the risk for SPC, especially for smoking-related SPCs in cancer survivors. Preventive measures are necessary to reduce not only SPC incidence but also tobacco use.     

Long-term population-based risks of breast cancer after childhood cancer

Previous studies have reported substantially increased risks of breast cancer among survivors of childhood cancer at 10-20 years posttreatment. Whether these excess risks are sustained beyond 40 years of age when general population incidence of breast cancer begins its steep increase is largely unknown. We quantified the risk of breast cancer in adult female survivors with considerably more survivors followed-up beyond 40 years of age than previously available. Standardized Incidence Ratios (SIR), Excess Absolute Risks (EAR), and cumulative incidence were calculated within a population-based cohort of 8,093 female survivors of childhood cancer. Poisson regression models were used to model SIRs and EARs in a multivariable setting. Eighty-one survivors developed a primary breast cancer, where 37.5 were expected (SIR= 2.2, 95% CI: 1.7-2.7). SIRs decreased significantly with increasing attained age (p(trend) < 0.001) to an SIR of 0.9 (95% CI: 0.5-1.8) at ages beyond 50 years; EARs increased significantly to about 40 years of age (p(trend) < 0.001) but then plateau. Between 30 and 49 years of age survivors experienced approximately 1 extra breast cancer per 1,000 survivors per year. Overall, 3% developed breast cancer by the age of 50. The substantially increased relative risks of breast cancer observed at 10-20 years postdiagnosis are not sustained into ages at which the risk of breast cancer in the general population becomes substantial. Among women who survived to an age of at least 50 years there is currently no evidence of an increased risk of breast cancer.     

Malignant melanoma, breast cancer and other cancers in patients with Parkinson's disease

Previous studies report an atypical cancer pattern among patients with Parkinson's disease. Here, we evaluate the cancer pattern among people diagnosed with Parkinson's disease in an extension of our previous cohort study. For this Danish population-based cohort study, we identified 20,000 people with Parkinson's disease diagnosed in 1977-2006, from the National Danish Hospital Register. Cohort members were followed up for cancer in the Danish Cancer Registry until December 31, 2008, and their incidence rates of cancer were compared to age-, sex- and calendar period-specific rates in the general population as standardized incidence rate ratios (SIRs). In subanalyses, we estimated the risk for cancer among patients with early onset Parkinson's disease and we also compared breast tumor characteristics among women with Parkinson's disease to that of a control group. The overall cancer risk in our cohort was decreased [SIR = 0.86; 95% confidence interval (CI) = 0.83-0.90], as were those for smoking-related (SIR = 0.65; 95% CI = 0.60-0.70) and nonsmoking-related cancers (SIR = 0.79; 95% CI = 0.71-0.86). The cohort had increased risks for malignant melanoma (SIR = 1.41; 95% CI = 1.09-1.80), nonmelanoma skin cancer (SIR = 1.29; 95% CI = 1.18-1.39) and female breast cancer (SIR = 1.17; 95% CI = 1.02-1.34). Among patients with early onset Parkinson's disease, the risk for cancer was comparable to that of the general population. Of breast tumor characteristics, only grade of malignancy differed between Parkinson's disease women and controls. This study confirms a lower cancer risk among people with Parkinson's disease. Increased risks for malignant melanoma, nonmelanoma skin cancer and breast cancer might be due to shared risk factors with Parkinson's disease.     

Primary Malignancy after Primary Female Breast Cancer in the South of the Netherlands, 1972–2001

Summary Objectives. To assess the risk of second primary cancers among women with previous breast cancer and calculate the excess burden of second cancer in the population. Methods. A population-based longitudinal study was conducted using the Eindhoven cancer registry data on 9919 breast cancer patients diagnosed in the period 1972–2000 and followed until 2001. Standardised incidence ratios (SIR) and absolute excess risks (AER) were calculated. Results. In total, 1298 (13%) women developed a second primary cancer. The risk of overall second cancer was higher among breast cancer patients compared to the general population (SIR: 2.8; 95% CI: 2.6–2.9), with an AER of 115 second cancers for every 10,000 breast cancer patients per year. High SIR and AER were observed for breast cancer (SIR: 4.1; 95% CI: 3.8–4.4; AER: 64/10,000 patients/year) and ovarian cancer (SIR: 2.0; 95% CI: 1.5–2.7; AER: 4.5/10,000 patients/year). Conclusions. Our recent data show that women with previous breast cancer have an elevated risk of developing a second cancer compared to the general population. Excess burden for the population is especially high for second cancers of the breast, ovary and colon. Screening may only be justified for breast, ovary and colon cancer in certain groups of patients.     

Increased risk of colon cancer after external radiation therapy for prostate cancer

Radiotherapy can induce second cancers. Controversies still exist regarding the risk of second malignancies after irradiation for prostate cancer. We evaluated the risk of developing colon and rectum cancers after prostate cancer in irradiated and nonirradiated patients. Using data from the population-based Geneva cancer registry, we included in the study all men with prostate cancer diagnosed between 1980 and 1998 who survived at least 5 years after diagnosis. Of the 1,134 patients, 264 were treated with external radiotherapy. Patients were followed for occurrence of colorectal cancer up to 31 December, 2003. We calculated standardized incidence ratios (SIR) using incidence rates for the general population to obtain the expected cancer incidence. The cohort yielded to 3,798 person-years. At the end of follow-up 19 patients had developed a colorectal cancer. Among irradiated patients the SIR for colorectal cancer was 3.4 (95% confidence intervals [CI] 1.7-6.0). Compared to the general population, the risk was significantly higher for colon cancer (SIR = 4.0, 95% CI: 1.8-7.6), but not for rectal cancer (SIR = 2.0, 95% CI: 0.2-7.2). The risk of colon cancer was increased in the period of 5-9 years after diagnosis (SIR = 4.7, 95% CI: 2.0-9.2). The overall SIR of secondary cancer in patients treated with radiotherapy was 1.35 (p = 0.056). Nonirradiated patients did not have any increased risk of rectal or colon cancer. This study shows a significant increase of colon but not rectum cancer after radiotherapy for prostate cancer. The risk of second cancer after irradiation, although probably small, needs nevertheless to be carefully monitored.     

Second Primary Tumors Following Thyroid Cancer a Swedish Record-Linkage Study

The incidence of second primary tumors was studied through record-linkage in 2 968 thyroid cancer patients reported to the Swedish Cancer Registry during the period 1958-1975. The cohort was matched with the Swedish Cancer Registry between 1959 and 1984. A total of 283 second primary tumors were reported more than one year after thyroid cancer diagnosis, and the standardized incidence ratio (SIR) was 1.18 (95% confidence interval = 1.03-1.31). A significantly elevated risk of cancer of the kidney, endocrine glands, and nervous system was noted. Men had a higher risk (SIR = 1.37; 95% CI = 1.06-1.70) than women (SIR = 1.11; 95% CI = 0.96-1.28). Patients who were 36-45 years at the time of the thyroid cancer diagnosis were at highest risk of developing a second primary tumor (SIR = 1.35; 95% CI = 0.99-1.81). Significantly elevated risks were seen 5-9 years after the thyroid cancer diagnosis (SIR = 1.44; 95% CI = 1.14-1.69), and the SIR was close to unity after ≥ 15 years of follow-up. Previously described elevated risks of subsequent leukemia and breast cancer were not confirmed in this study. Close medical surveillance, thyroid cancer treatment, hereditary factors, and a high frequency of autopsy could all contribute to the elevated risk of a second primary tumor in these patients.     

A population-based study on the risk of cervical cancer and cervical intraepithelial neoplasia among grand multiparous women in Finland

Previous studies suggest that high parity increases the risk of cervical cancer. We studied the risk of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN3) in a Finnish cohort of grand multiparous (GM) women (at least five children) with low prevalence of sexually transmitted infections (STI). The Finnish Cancer Registry data revealed 220 CC and 178 CIN3 cases among 86 978 GM women. Standardised incidence ratios (SIR) were calculated from the numbers of observed and expected cases. Interval analyses by parity, age at first birth and average birth interval were done using multivariate Poisson regression. Seroprevalence of human papillomavirus (HPV) 16 and Chlamydia trachomatis was tested among 561 GM women and 5703 women with 2-4 pregnancies. The incidence among GM women was slightly above the national average for squamous cell carcinoma of cervix uteri (SIR 1.21, 95% CI 1.05-1.40) and CIN3 (1.37, 95% CI 1.17-1.58), but lower for adenocarcinoma (SIR 0.77, 95% CI 0.52-1.10). The seroprevalence of HPV16 and Chlamydia trachomatis among GM women was lower than in the reference population, except among those women who had their child under age 19. Age under 20 years at first birth increased the risk of CC and CIN3 especially in premenopausal GM women, while increasing parity had no effect. The small relative risks of CC and CIN3 among GM women in our study as compared to studies from other countries can be explained by the exceptionally low prevalence of STIs in Finnish GM women. The observed SIRs between 1.2 and 1.4 should be interpreted to represent increased risk attributable to grand multiparity. The increased incidence of CC and CIN3 among young GM women suggests causal association to HPV 16 and Chlamydia trachomatis infections.     

Cancer risks in thyroid cancer patients.

Cancer risks were studied in 834 thyroid cancer patients given 131I (4,551 MBq, average) and in 1,121 patients treated by other means in Sweden between 1950 and 1975. Record-linkage with the Swedish Cancer Register identified 99 new cancers more than 2 years after 131I therapy [standardised incidence ratio (SIR) = 1.43; 95% confidence interval (CI) 1.17-1.75] vs 122 (SIR = 1.19; 95% CI 0.88-1.42) in patients not receiving 131I. In females treated with 131I overall SIR was 1.45 (95% CI 1.14-1.83) and significantly elevated were noted for tumours of the salivary glands, genital organs, kidney and adrenal gland. No elevated risk of a subsequent breast cancer or leukaemia was noted. SIR did not change over time, arguing against a strong radiation effect of 131I. Organs that were estimated to have received more than 1.0 Gy had together a significantly increased risk of a subsequent cancer following 131I treatment (SIR = 2.59; n = 18). A significant trend was seen for increasing activities of 131I with highest risk for patients exposed to greater than or equal to 3,664 MBq (SIR = 1.80; 95% CI 1.20-2.58). No specific cancer or group of cancers could be convincingly linked to high-dose 131I exposures since SIR did not increase after 10 years of observation. However, upper confidence intervals could not exclude levels of risk that would be predicted based on data from the study of atomic bomb survivors. We conclude that the current practice of extrapolating the effects of high-dose exposures to lower-dose situations is unlikely to seriously underestimate radiation hazards for low LET radiation.     

Risk of second non-hematological malignancies among 376,825 breast cancer survivors

Breast cancer survivors are at increased risk of treatment-related second cancers. This study is the first to examine risk 30 or more years after diagnosis and to present absolute risks of second cancer which accounts for competing mortality. We identified 23,158 second non-hematological malignancies excluding breast in a population-based cohort of 376,825 one-year survivors of breast cancer diagnosed from 1943 to 2002 and reported to four Scandinavian cancer registries. We calculated standardized incidence ratios (SIR) and utilized a competing-risk model to calculate absolute risk of developing second cancers. The overall SIR for second cancers was 1.15 (95% confidence interval [CI] = 1.14–1.17). The SIR for potentially radiotherapy-associated cancers 30 or more years after breast cancer diagnosis was 2.19 (95% CI = 1.87–2.55). However, the largest SIRs were observed for women aged <40 years followed for 1–9 years. At 20 years after breast cancer diagnosis, the absolute risk of developing a second cancer ranged from 0.6 to 10.3%, depending on stage and age; the difference in the absolute risk compared to the background population was greatest for women aged <40 years with localized disease, 2.3%. At 30 years post breast cancer diagnosis, this difference reached 3.2%. These risks were small compared to the corresponding risk of dying from breast cancer. Although the absolute risks were small, we found persistent risks of second non-hematological malignancies excluding breast 30 or more years after breast cancer diagnosis, particularly for women diagnosed at young ages with localized disease.     

Association between adult weight gain and colorectal cancer: A dose–response meta‐analysis of observational studies

This study investigated the association between adult weight gain and risk of colorectal cancer (CRC). Using terms related to weight gain and CRC, we searched PubMed, Embase and Web of Science for relevant studies published before June 2014. Two evaluators independently selected studies according to the selection criteria, and eight studies were included (three case–control and five cohort studies). Summary estimates were obtained using fixed‐ or random‐effects models. The relative risk (RR) of the association between adult weight gain and CRC was 1.25 (95% confidence interval [CI], 1.10–1.43); the RR was 1.30 (95% CI, 1.14–1.49) for colon cancer (CC) and 1.27 (95% CI, 1.02–1.58) for rectal cancer (RC) for the highest versus lowest category. For every 5‐kg increase in adult weight, the risk increased by 5% (RR, 1.05; 95% CI, 1.02–1.09) for CRC, 6% (RR, 1.06; 95% CI, 1.02–1.11) for CC and 6% (RR, 1.06; 95% CI, 1.03–1.08) for RC. The subgroup analyses showed a positive association between adult weight gain and risk of CRC only in men, and the RR was 1.65 (95% CI, 1.42–1.92) for the highest versus lowest category of adult weight gain and 1.10 (95% CI, 1.06–1.15) for a 5‐kg increase in adult weight. In conclusion, there is evidence that adult weight gain is associated with an increased risk of CRC. However, the positive association between adult weight gain and risk of CRC is stronger among men than among women.     

Second malignancies among survivors of germ-cell testicular cancer: a pooled analysis between 13 cancer registries

We investigated the risk of second malignancies among 29,511 survivors of germ-cell testicular cancer recorded in 13 cancer registries. Standardized incidence ratios (SIRs) were estimated comparing the observed numbers of second malignancies with the expected numbers obtained from sex-, age-, period- and population-specific incidence rates. Seminomas and nonseminomas, the 2 main histological groups of testicular cancer, were analyzed separately. During a median follow-up period of 8.3 years (0-35 years), we observed 1,811 second tumors, with a corresponding SIR of 1.65 (95% confidence interval (CI): 1.57-1.73). Statistically significant increased risks were found for fifteen cancer types, including SIRs of 2.0 or higher for cancers of the stomach, gallbladder and bile ducts, pancreas, bladder, kidney, thyroid, and for soft-tissue sarcoma, nonmelanoma skin cancer and myeloid leukemia. The SIR for myeloid leukemia was 2.39 (95% CI: 1.41-3.77) after seminomas, and 6.77 (95% CI: 4.14-10.5) after nonseminomas. It increased to 37.9 (95% CI: 18.9-67.8; based on 11 observed cases of leukemia) among nonseminoma patients diagnosed since 1990. SIRs for most solid cancers increased with follow-up duration, whereas they did not change with year of testicular cancer diagnosis. Among subjects diagnosed before 1980, 20 year survivors of seminoma had a cumulative risk of solid cancer of 9.6% (95% CI: 8.7-10.5%) vs. 6.5% expected, whereas 20 years survivors of nonseminoma had a risk of 5.0% (95% CI: 4.2-6.0%) vs. 3.1% expected. In conclusion, survivors of testicular cancers have an increased risk of several second primaries, where the effect of the treatment seems to play a major role.     

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non-melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.     

Cancer risk after radiotherapy for breast cancer

Among women with breast cancer, we compared the relative and absolute rates of subsequent cancers in 1541 women treated with radiotherapy (RT) to 4570 women not so treated (NRT), using all registered in the Swiss Vaud Cancer Registry in the period between 1978 and 1998, and followed up to December 2002. Standardised incidence ratios (SIRs) and the corresponding 95% confidence intervals (CIs) were based on age- and calendar year-specific incidence rates in the Vaud general population. There were 11 lung cancers in RT (SIR = 1.40; 95% CI: 0.70-2.51) and 17 in NRT women (SIR = 0.76; 95% CI: 0.44-1.22), 72 contralateral breast cancers in RT (SIR = 1.85; 95% CI: 1.45-2.33) and 150 in NRT women (SIR = 1.38; 95% CI: 1.16-1.61), and 90 other neoplasms in RT (SIR = 1.37; 95% CI: 1.10-1.68) and 224 in NRT women (SIR = 1.05; 95% CI: 0.91-1.19). Overall, there were 173 second neoplasms in RT women (SIR = 1.54, 95% CI: 1.32-1.78) and 391 among NRT women (SIR = 1.13, 95% CI: 1.02-1.25). The estimates were significantly heterogeneous. After 15 years, 20% of RT cases vs 16% of NRT cases had developed a second neoplasm. The appreciable excess risk of subsequent neoplasms after RT for breast cancer must be weighed against the approximately 5% reduction of breast cancer mortality at 15 years after RT.     

Risk of new primary cancer in patients with oropharyngeal cancer.

The relative risk of subsequent cancers was evaluated for a total of 9,092 patients with lip and oropharyngeal cancer recorded between 1953 and 1989 in the nationwide Finnish Cancer Registry. The observed numbers of patients were compared with those expected on the basis of the incidence rates in the Finnish population. There were 1,130 patients (12%) with a new cancer. The standardised incidence ratio (SIR) of contracting a new primary cancer was 1.2 for lip cancer patients (95% CI 1.1-1.3) and 1.4 for patients with oropharyngeal cancer (95% CI 1.2-1.4). Among lip cancer patients, a statistically significant excess risk was found for subsequent cancers in the oropharyngeal area (SIR 1.9, 95% CI 1.1-3.1), larynx (SIR 2.0, 95% CI 1.2-2.9) and lung (SIR 1.4, 95% CI 1.3-1.6), i.e. for cancers with tobacco aetiology. Among patients with oropharyngeal cancer there was an excess of lip cancer (SIR, 3.5, 95% CI 1.5-6.9), lung cancer (SIR 1.8, 95% CI 1.3-2.3) and leukaemia (SIR 2.3, 95% CI 1.0-4.3). Radiotherapy for the first primary did not increase the risk of new cancer.