Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case-control study

Abstract

Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatrogenic effects must be carefully examined. We have investigated the association between endometrial cancer and tamoxifen use or other treatments in women treated for breast cancer in a case‐control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast cancer and hospital and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk increased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. Women who had undergone pelvic radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001). After adjusting for confounding factors, the risk was higher for tamoxifen users (p = 0.0012), treatment for more than 3 years (all p < 0.03) and pelvic radiotherapy (p = 0.012). Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a causal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention. Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. Endometrial cancers diagnosed in women treated with tamoxifen have poorer prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long‐term evaluation of the risk–benefit ratio of tamoxifen as a preventive treatment for breast cancer is clearly warranted. Int. J. Cancer 76:325–330, 1998.© 1998 Wiley‐Liss, Inc.

The effects of tamoxifen on proliferation and steroid receptor expression in postmenopausal endometrium

“…In larger epidemiological studies, the relative risk of endometrial carcinoma is estimated to be two to threefold, the risk increasing with the duration and the cumulative dose of tamoxifen treatment. [2][3][4][5][6][7] In postmenopausal women tamoxifen exerts a proliferative effect on the endometrium, as measured by the hyperdiploid fraction, 8 and clinical studies have reported an increased incidence of endometrial polyps and hyperplastic endometrial changes, mostly interpreted as evidence of the agonistic effect of tamoxifen. [9][10][11][12][13][14] Histology of tamoxifen exposed postmenopausal endometrium in general shows a characteristic picture of a condensated, hypercellular, collagen rich stroma, whereas the glandular epithelium stays thin and atrophic or metaplastic, the flattened epithelium lining cystically dilated glands or polyps.…”

Sarcomas de útero después de tratamiento con tamoxifeno por cáncer de mama

“…No obstante no se aconseja su uso durante más de cinco años por el riesgo de cáncer sobre el endometrio 6 . La patología endometrial es más frecuente en mujeres con cáncer de mama tratadas con tamoxifeno que en las no tratadas 7 , existen múltiples publicaciones que demuestran un incremento del riesgo relativo del cáncer endometrial en mujeres con cáncer de mama tratadas con tamoxifeno versus las no tratadas [7][8][9][10][11] , Odds Ratio (OR) = 2.4, 95% Intervalo de Confianza (CI) = 1.8-3.0 e íntimamente relacionado con la duración del tratamiento; si comparamos tratadas más de 5 años con no tratadas el riesgo aumenta OR = 3.6 95% CI = 2.6-4.8.…”

“…9 12 . La mayoría de los carcinomas diagnosticados son endometrioides o adenocarcinomas como ocurre en nuestra serie 9,13 .…”

“…La mayoría de los carcinomas diagnosticados son endometrioides o adenocarcinomas como ocurre en nuestra serie 9,13 . En estudios recientes se ha puesto de manifiesto que los cánceres endometriales en postmenopáusi-cas con cáncer de mama y tratadas con tamoxifeno, fueron de diagnóstico en estadio más avanzado y de peor pronóstico que los tumores que desarrollaban las pacientes no tratadas con tamoxifeno 7,9,11,14,15 . Las dos pacientes descritas en nuestra casuística tuvieron una evolución muy desfavorable.…”

Tamoxifen Treatment and Risk of Endometrial Cancer: An Overview

“…The risk of developing endometrial cancer in patients treated with tamoxifen is dose and duration dependent [26][27][28][29][30].…”