Tamoxifen exposure and risk of oesophageal and gastric adenocarcinoma: a population-based cohort study of breast cancer patients in Sweden

Abstract

In a population-based cohort study of all women aged over 50 years with breast cancer in the Swedish Cancer Register in 1961 -2003, those diagnosed before 31 December 1987 were regarded as unexposed to tamoxifen, whereas those diagnosed after that date were considered potentially exposed. Crosslinkages within the Cancer Register and the Registers of Death and Emigration enabled follow-up. Standardised incidence ratios (SIRs) of oesophageal and gastric cancer represented relative risks. Among 138 885 cohort members contributing with 1 075 724 person-years of follow-up, we found a nonsignificantly increased risk of oesophageal adenocarcinoma during the potential tamoxifen exposure period (SIR 1.60, 95% confidence interval (CI) 0.83 -3.08), but the risk estimates decreased with increasing latency interval. No association was observed during the unexposed period. No increased risk of cardia adenocarcinoma was identified in either period. The risk of non-cardia gastric adenocarcinoma was increased in the potential tamoxifen period (SIR 1.27, 1.03 -1.57), and almost doubled (SIR 1.86, 95% CI 1.10 -3.14) in the period of longest latency (10 -14 years). The corresponding overall SIR was increased in the unexposed group also, but here SIR did not increase with longer latency intervals. An increased risk of tobacco-related tumours, that is, oesophageal squamous-cell carcinoma and lung cancer, was limited to the unexposed cohort, indicating that confounding by smoking might explain the increased SIR during the unexposed period. We concluded that there might be a link between tamoxifen and risk of non-cardia gastric adenocarcinoma.

Sex-specific risk factor profile in oesophageal adenocarcinoma

“…A possible explanation might be that women are exclusively protected from developing oesophageal adenocarcinoma by some yet unidentified factors, for example, female sex hormones. A protective role of oestrogen has been evaluated in some studies, but with no clear evidence of the effect, although the statistical power was limited (Lagergren and Jansson, 2005;Chandanos et al, 2006). However, a UK case -control study noted a decreased risk among women with a history of breast feeding (Cheng et al, 2000).…”

Metachronous Multiple Primary Malignant Neoplasms of the Stomach and the Breast: Report of Two Cases With Review of Literature

“…In the cancer registry-based retrospective study by the Karolinska Institute over a period of 40 years, the incidence of second primary malignancy in noncardia stomach was 41% higher compared with the general population. 5 Ellis et al 6 reported an incidence of 0.15% for the development of second primary malignancy in the stomach. Several authors have reported on a lesion in the stomach being labeled as a second primary malignancy and then subsequently found to be metastasis.…”

“…Thus, a harmful effect of antiestrogen therapy is the risk of developing gastric noncardia adenocarcinoma. 5 The importance of the differentiation between second primary malignancy and metastasis cannot be overstressed, because the treatment radically differs between the two. Although a second primary malignancy has to be offered surgery as first-line treatment with curative intent, the treatment of metastatic tumor is by systemic chemotherapy with a uniformly poor prognosis.…”

Chemoprevention of Adenocarcinoma Associated with Barrett’s Esophagus: Potential Options

“…However, population-based studies were not able to show a significant association of hormone replacement therapy with the risk of EAC [67,68] .…”