Objectives: The aim of the retrospective cohort study was to evaluate the relationship between the influence of tamoxifen on the development of endometrial and other second primary cancers in the patients with invasive breast cancer.
Study design: A cohort of 630 women diagnosed with breast cancer from 1987 to 1994 was selected from a population-based registry; 440 patients were treated with tamoxifen and 190 patients without it. The observation period was 8.5 years (range 5-12 years). The data were analysed by the relative risk (RR) calculation at a confidence interval (CI) of 95%, using a Mantel-Haenszel chi(2)-test and Fisher's p-test to evaluate statistical significance.
Results: There were no statistically significant differences between the group of breast cancer patients treated with tamoxifen and without it as regards the age at the breast cancer diagnosis, family medical histories, body mass, age at menopause, fertility, diabetes, hormone replacement therapy and oestrogen-hormone replacement therapy. In 41/440 (9.3%) tamoxifen-treated patients and in 8/190 (4.2%) non-users of tamoxifen, diagnostic curettage was performed due to benign endometrial changes and endometrial cancer (EC). The difference in the proportions of patients with diagnostic curettage in both group was statistically significant (chi(2)=4.45, p=0.03). In the group of patients treated with tamoxifen, with the median treatment duration of 40 months (range 1-97 months) and in the group of patients without tamoxifen, EC was diagnosed in 11 and in two patients, respectively. The evaluated RR was 2.38 (0.53-10.61, 95% CI). The second primary cancer, excluding contralateral breast cancer and EC, was diagnosed in the group of breast cancer patients treated with tamoxifen and without it in almost the same percentage, i.e. in 12 patients (3%) in the group of patients who were treated with tamoxifen and in 10 patients (5%) in the group of patients without tamoxifen treatment.
Conclusion: Despite the fact that the calculated RR of EC in our study (2.4) was not statistically significant, due to a small number of patients, our results support the IARC evaluation that tamoxifen is carcinogenic to humans. Our data also suggest that tamoxifen does not increase the risk of other second primary cancers. However, the risk of individual second primary cancers cannot be reliably assessed due to a limited number of patients.