Dror Yigael

Endometrial changes in postmenopausal women treated with tamoxifen for breast cancer

Objective To evaluate whether risk factors, other than tamoxifen, can be identified for the development of endometrial pathologies in postmenopausal breast cancer patients treated with tamoxifen.

High Frequency of Adenomyosis in Postmenopausal Breast Cancer Patients Treated with Tamoxifen

Pathologic evaluation for adenomyosis in uterine specimens as well as demographic characteristics, health habits and risk factors for endometrial cancer were compared in 28 postmenopausal breast cancer patients with tamoxifen (TAM) treatment and in 11 similar patients without TAM treatment in order to determine the association between postmenopausal TAM exposure and the frequency of adenomyosis. The same comparison was also made between TAM-treated patients with adenomyosis and TAM-treated patients without adenomyosis. Adenomyosis was histologically diagnosed in 53.6% TAM-treated patients and in 18.2% non-TAM patients. Overall, there were no significant statistical differences in all parameters tested between the 2 groups, as well as between the TAM-treated patients with adenomyosis and the TAM-treated patients without adenomyosis. It can be concluded that adenomyosis was significantly more common among postmenopausal breast cancer patients who were treated with TAM as compared to similar patients without TAM treatment (p = 0.0186). This significant high rate of adenomyosis may be attributed to the continuous and unopposed exposure to TAM. It is, however, impossible to predict which postmenopausal breast cancer patient will develop adenomyosis after treatment with TAM.

Time-dependent effect of tamoxifen therapy on endometrial pathology in asymptomatic postmenopausal breast cancer patients.

Various endometrial lesions were more frequent among asymptomatic postmenopausal breast cancer patients who were treated with tamoxifen for > 48 consecutive months (30.8%) when compared with similar patients who were treated for 6-24 months or for 25-48 months (20.8% and 12.5%, respectively). However, this difference was not statistically significant. There were also no significant differences in the frequency of the various endometrial lesions between these three groups, although endometrial polyps were more frequently found among those treated for > 48 months. Overall, 20.7% of the 164 tamoxifen-treated patients in the study had an endometrial pathology. It can be concluded that there is a slight tendency among those postmenopausal patients who have been treated for > 48 consecutive months to have a higher frequency of endometrial lesions.

Common endometrial decidual reaction in postmenopausal breast cancer patients treated with tamoxifen and progestogens.

In order to assess endometrial reaction to the combined treatment of tamoxifen and progestogens in asymptomatic postmenopausal breast cancer patients, we evaluated all such patients by vaginal ultrasonography and by histological examination of endometrial samplings. All patients were initially treated with tamoxifen, and progestogens were then added when metastases became evident. Of 12 patients included in the study, eight (66.66%) showed evidence of strong endometrial stromal decidualization, while three (25%) had decidual reactions in endometrial polyps. Overall, 11 (91.66%) of the patients had decidual reactions, and all were treated with progestogens for > or = 3 consecutive months. One patient, treated with progestogens for 1 months, had an inactive endometrium. All but three had thickened endometria (> 10 mm) on ultrasonographic evaluation. These data show that postmenopausal breast cancer patients who received progestogens for < or = 3 months, and who concomitantly took tamoxifen, had a uniform decidual reaction in all uteri.

Different Coexisting Gynecological and Endometrial Pathologies in Postmenopausal Breast Cancer Patients Treated with Tamoxifen

Tamoxifen administration to postmenopausal women has been described as being associated with various endometrial and other gynecological pathologies. However, different coexisting gynecological pathologies in such patients have not yet been described. In the present study, we assessed the histopathological conditions diagnosed in endometrium, myometrium, and ovaries of 28 postmenopausal breast cancer patients who were treated with tamoxifen (study group) and compared the findings to those obtained from 14 similar patients without tamoxifen treatment (control group I) and from 28 age-matched healthy postmenopausal controls (control group II). All specimens were removed by total abdominal hysterectomy and bilateral salpingo-oophorectomy for various indications. The overall incidence of two or more different coexisting gynecological pathologies was significantly higher among the study group (92.9%) than in control group I or in control group II (42.9 and 50%, respectively; p = 0.0001). There was no significant statistical difference between the control groups. Overall endometrial (and endometrial-like) origin of pathological conditions was significantly more common in the study group (92.6%) than in control group I (50%; p = 0.00072) and control group II (32.1%; p = 0.0000), while there was no significant difference between the latter two groups. These findings suggest that there might be an association between postmenopausal tamoxifen exposure and the development of such different coexisting or specific single gynecological pathologies originating from the endometrium.

Estrogen and Progesterone Receptors in Benign Ovarian Tumors of Menopausal Breast Cancer Patients Treated with Tamoxifen

In order to assess possible ovarian cell potential for interaction with tamoxifen, thus demonstrating possible effects of this agent on the development of ovarian pathologies through growth stimulation and cell proliferation, we measured estrogen receptors (ER) and progesterone receptors (PR) by immunohistochemical method in 16 benign ovarian tumors removed from 11 postmenopausal breast cancer patients treated with tamoxifen (study group). The results were compared with those measured in 7 similar ovarian tumors obtained from 5 similar patients without tamoxifen treatment (control group I), and in 9 similar tumors removed from 9 age-matched postmenopausal women (control group II). There were no significant differences with regard to ER or PR expression between the study group and control group I and II (ER = 18.75, 0.0 and 11%, respectively; PR = 43.75, 28.5 and 44%, respectively; p = NS). There were also no significant statistical differences between the three groups when subdividing the ovarian pathologies according to different histological types. From the results obtained in this study, it seems that tamoxifen probably does not have any direct influence on the ovaries of menopausal breast cancer patients.