1 Cancer Epidemiology Unit and Cancer Registry of Vaud, Institut Universitaire de Médecine Sociale et Préventive, Lausanne; 2 Cancer Registry of Neuchâtel, Neuchâtel, Switzerland; 3 Laboratory of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, Milan; 4 Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy
Received 5 August 2002; accepted 28 August 2002
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Abstract |
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Excess risks of several second neoplasms following breast cancer have been reported. However, these risks have still to be quantified.
Patients and methods:
We considered 9729 breast cancer patients registered by the Swiss Cancer Registries of Vaud and Neuchâtel (covering about 786 000 inhabitants) and followed up from 1974 to 1998.
Results:
Overall, 443 second primary neoplasms (other than second primary breast cancers) were observed versus 389 expected [standardised incidence ratio (SIR): 1.14; 95% confidence interval (CI) 1.041.25]. The SIRs were above unity for endometrium (SIR = 1.5), ovary (1.3), colorectum (1.1), gallbladder (1.4), cutaneous malignant melanoma (1.4), kidney (1.4), lymphomas (1.4) and leukaemias (1.2), as well as for selected tobacco-related neoplasms. The largest excess risk was found for soft tissue sarcomas (STS) with 10 cases observed versus 3.1 expected (SIR = 3.2; 95% CI 1.55.9). Of these, eight occurred in potentially irradiated areas.
Conclusions:
This analysis confirms the existence of a modest excess in several neoplasms occurring after breast cancer. The substantial excess of STS confirms the strong association between irradiation and STS.
Key words: breast cancer, follow-up study, population-based, second primary cancer, soft-tissue sarcoma, standardised incidence ratio
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Introduction |
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A large study of 141 053 women with invasive breast cancer registered in Sweden from 1958 to 1997, and followed-up to December 1997, found an excess risk of lung cancer [standardised incidence ratio (SIR) = 1.32] [6] following breast cancer. The risk tended to rise with increasing time since breast cancer diagnosis and was attributed to an interaction between radiotherapy and smoking habits in subsequent cohorts of women.
We considered second primary cancers in breast cancer patients diagnosed in Vaud from 1974 to 1994 [7]. To provide further information on the issue of second primary neoplasms of the lung and other sites, we can now produce a similar analysis of the Neuchâtel Cancer Registry together with the Vaud Cancer Registry, and extend the follow-up to 1998.
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Patients and methods |
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After exclusion of 29 cases detected at autopsy, 21 at death, 161 by death certification alone, 845 followed-up for <1 month and of synchronous cancers (i.e. within 1 month after the first primary; n = 37), the present series comprised 9729 invasive breast cancers diagnosed from 1974 to 1998 (rate of histological verification: 97.8%). These women were followed-up to the end of 1998 for the occurrence of second primary neoplasms, emigration or death, for a total of 61 834 person-years at risk. Calculation of expected number of cases was based on register, site, age and calendar period specific incidence rates, multiplied by the corresponding number of person-years at risk. The significance of the observed:expected ratios (SIR) and the corresponding 95% confidence intervals (CI) was based on the Poisson distribution.
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Results |
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Overall, 443 second primary neoplasms were observed versus 389 expected, corresponding to an SIR of 1.14 (95% CI 1.041.25). The SIR was 1.04 for <5 years and 1.25 (95% CI 1.091.42) for 5 years since the original diagnosis of breast cancer.
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Discussion |
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The main finding of the present analysis is, however, a substantial excess of STS in women diagnosed with breast cancer. An excess of breast cancer following STS has been reported in North West England [11]. Common correlates of breast cancer and STS, including reproductive factors [12] and overweight [13], may partly explain the excess risk. Most STSs, however, occurred in the thorax, shoulder and pelvis, i.e. in irradiated areas, and are probably the late consequences of radiotherapy, which could be documented through the cancer registries files for five out of eight cases located in potentially irradiated areas, and for none out of the two remaining cases. The age distribution of breast and second primary cancers is inconsistent with the classic LiFraumeni syndrome [14]. They confirm, nonetheless, the strong association between irradiation and STS, which appears to be mediated by variable susceptibility (i.e. germ-line mutation of the tumour suppressor gene p53) in family members [14].
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Acknowledgements |
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Footnotes |
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References |
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