Elsevier

European Journal of Cancer

Volume 41, Issue 15, October 2005, Pages 2331-2337
European Journal of Cancer

Risks of second primary breast and urogenital cancer following female breast cancer in the south of The Netherlands, 1972–2001

https://doi.org/10.1016/j.ejca.2005.01.029Get rights and content

Abstract

A cohort of 9919 breast cancer patients from the population-based Eindhoven Cancer Registry was followed for vital status and development of second cancer. Person-year analysis was applied to determine the risk of second primary breast or urogenital cancer among breast cancer patients and to assess its correlation with age, treatment and time since the first breast cancer diagnosis. Women with previous breast cancer have an elevated risk of overall second breast or urogenital cancer. The largest relative risk was observed for second breast cancer (SIR (standardised incidence ratio) 3.5; 95% confidence interval (CI) 3.2–3.8) and second ovarian cancer (SIR 1.7; 95% CI 1.2–2.3). The absolute excess risk was highest for second breast cancer (64/10,000 patients/year). However, breast cancer has an inverse relationship to risk of cervical cancer. Changes in behavioural risk factors are important for lowering the risk of second cancer after breast cancer.

Introduction

A history of breast cancer is a risk indicator for second primary cancer among women, especially for second primary breast and genital cancer. Higher risks have been found of second breast cancer 1, 2, subsequent ovarian cancer [2] and uterine cancer 3, 4 after primary breast cancer [5]. However, the association with cervical cancer and cancer of the vagina-vulva has not been studied in detail [2]. Only a few studies have shown an increased risk of second primary kidney and bladder cancer among breast cancer patients 6, 7.

Examination of the association between breast cancer and second primary cancer may contribute to the development of preventive interventions. Understanding these issues may also help identify the treatment that carries the lowest risk of second cancer for breast cancer patients. In addition, it may also contribute to early detection of second cancer. Common risk factors, such as dietary habits, reproductive characteristics, exposure to exogenous oestrogen and genetic factors play an important role in the aetiology of second female cancers, particularly breast, uterine and ovarian cancer [8]. Breast cancer treatments, such as radiotherapy, systemic chemotherapy 6, 9 and hormonal therapy, may be associated with a higher risk of certain second primary cancers among breast cancer patients. In addition, hormonal therapy with tamoxifen has been found to increase the risk of cancer of the uterus, in particular mixed mullerian tumours 10, 11, 12.

The effect of factors such as latency time, cancer treatment and age at diagnosis on the risk of second female cancer remains unknown. Our cohort comprises the most recent data, with a long follow-up time and a large number of cases. This enables us to assess the role of important risk factors in the development of second primary cancer. The aim of this population-based cohort study was to determine the incidence of second primary breast and urogenital cancers among breast cancer patients in the south of The Netherlands, compared with the incidence expected in the general population, and to relate this incidence to the initial breast cancer treatment, follow-up time and age at breast cancer diagnosis.

Section snippets

Patients

Breast cancer patients were selected from the Eindhoven Cancer Registry in the south of The Netherlands. This is a population-based cancer registry, which covered almost 2.3 million individuals in 2004. A detailed description of the data collection has been reported elsewhere [13].

We excluded patients with less than 1 year of follow-up time (n = 1458), patients with in situ primary breast cancer (n = 458), patients with other malignancies diagnosed before breast cancer, as well as patients with a

Results

Our cohort yielded 65,950 person-years. General characteristics at the time of primary breast cancer diagnosis are shown in Table 1. The average age at breast cancer diagnosis was 58.8 years, the average follow-up time was 6.6 years, and the median follow-up time was 4.9 years. Overall, 725 breast cancer patients developed second breast and urogenital cancer, compared with the expected 266 patients in the population (SIR 2.7; 95% CI 2.5–2.9) (Table 2). The relative risk of developing second

Discussion

Our results suggest that women diagnosed with a primary breast cancer are at increased risk of developing a second breast and ovarian cancer. This is in line with previous studies 1, 4, 5, 6, 16, 17. Elevated risks were particularly marked among pre-menopausal women. In the south of The Netherlands (area of Eindhoven Cancer Registry), every year 11 of every 1000 breast cancer patients develop a second cancer (I. Soerjomataram, Netherlands Institute of Health Sciences), half of which are second

Acknowledgement

We thank Professor F.E. van Leeuwen for her valuable comments and advice.

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