1 Unité d'Epidémiologie du Cancer, Institut Universitaire de Médecine Sociale et Préventive, Bugnon 17, 1005 Lausanne; 2 Registre Vaudois des Tumeurs, Institut Universitaire de Médecine Sociale et Préventive, CHUV-Falaises 1, 1011 Lausanne; 3 Registre Neuchâtelois des Tumeurs, avenue de Cadolles 7, 2000 Neuchâtel, Switzerland; 4 Istituto di Biometria e Statistica Medica, Università degli Studi di Milano, via Venezian 1, 20133 Milan; 5 Istituto di Ricerche Farmacologiche Mario Negri, via Eritrea 62, 20157 Milan, Italy
* Correspondence to: Dr F. Levi, Registre Vaudois des Tumeurs, CHUV-Falaises 1, CH 1011 Lausanne, Switzerland. Tel: +41-21-3147311; Fax: +41-21-3230303; E-mail: fabio.levi{at}chuv.ch
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Abstract |
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Patients and methods: We considered esophageal cancer risk among 11 130 breast cancer patients diagnosed between 1974 and 2002 in the Swiss cantons of Vaud and Neuchâtel, and followed-up to the end of 2002, for a total of 75 900 women-years at risk.
Results: Overall, 18 cases were observed compared with 8.9 expected, corresponding to a standardised incidence ratio (SIR) of 2.0 [95% confidence interval (CI) 1.23.2]. The SIR was 1.6 in the first 10 years after diagnosis and 3.3 for 10 years after diagnosis, 2.3 for cases diagnosed between 1974 and 1988 and 1.5 for those diagnosed after 1988, 2.3 (based on 15 cases) for squamous cell cancer and 1.3 (based on three cases) for adenocarcinomas, and 2.9 for the upper third, 2.3 for the middle third and 1.9 for the lower third of the esophagus.
Conclusions: These data confirm an excess esophageal cancer risk following treatment for breast cancer which could not be explained by confounding of tobacco or alcohol alone. The excess risk tended to decrease for cases diagnosed after 1988, leaving open the issue of the risk of modern radiotherapy for breast cancer on esophageal cancer.
Key words: breast neoplasms, esophageal neoplasms, radiotherapy, second primary neoplasms
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Introduction |
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The US Surveillance Epidemiology and End Results (SEER) Program also provided estimates of esophageal cancer risk following adjuvant radiation therapy for breast cancer [4, 5
]. In the period 19732000, 171 cases of squamous cell esophageal cancer were registered, and the RR was 1.04 in the first 4 years after breast cancer diagnosis, 2.86 from 5 to 9 years and 1.81 for
10 years after breast cancer [4
]. The excess risk was mainly due to cancers in the upper and middle third of the esophagus. No excess risk was observed for adenocarcinomas. Other reports of esophageal cancer following radiotherapy for breast cancer are based on case reports, and therefore cannot provide estimates of risk [6
8
].
To provide further information on this issue [1], we used the datasets of the Swiss Vaud and Neuchâtel Cancer Registries, which include data concerning incident cases of malignant neoplasms in the two cantons.
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Materials and methods |
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After exclusion of 20 breast cancer cases detected at autopsy and 21 at death, 181 by death certification alone, and synchronous cancers (i.e. within 2 months after the first primary) (n = 1), the present series comprised 11 130 breast cancers diagnosed between 1974 and 2002. These women were followed-up to the end of 2002 for the occurrence of a second primary esophageal neoplasm, emigration outside the registration areas or death, for a total of 75 900 women-years at risk. Calculation of expected numbers of esophageal primaries were based on age-specific and calendar-year-specific incidence rates multiplied by the corresponding number of women-years at risk. The significance of the observed-to-expected ratios [standardized incidence ratio (SIR)] and their corresponding 95% CIs were based on the Poisson distribution [13].
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Results |
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Discussion |
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These limitations notwithstanding, the present dataset confirms that esophageal cancer risk is increased >2-fold in women treated for breast cancer. Alcohol drinking is associated with both breast [14, 15
] and esophageal cancer [16
], with a direct doserisk relation, and may have biased or modified the risk estimates. However, alcohol alone is unlikely to explain a >2-fold excess of esophageal cancer, particularly since the risk of other alcohol-related neoplasms (oral cavity and pharynx, larynx and liver) were not elevated in the same dataset [1
]. Tobacco, in contrast, is unlikely to have introduced any material bias, since smoking is not related to breast cancer [15
, 17
], and lung cancer incidence was not increased after breast cancer in the same dataset [1
]. Similarly, it is unlikely that surveillance bias has played any material role on these estimates, given the serious and almost invariably fatal prognosis of esophageal cancer [18
].
This study also suggests that the excess risk is not significantly different for adenocarcinomas and squamous cell cancers, or for various esophageal subsites, although the numbers are inadequate for any conclusion. The esophageal cancer risk tended to decrease for cases diagnosed after 1988 compared with those diagnosed earlier, but this study has inadequate statistical power to address the issue of change in risk over time. Consequently, available data are unable to address the risk, if any, of modern radiotherapy [19] for breast cancer on esophageal carcinogenesis.
Received for publication April 22, 2005. Revision received June 14, 2005. Accepted for publication June 22, 2005.
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References |
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