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Indian Journal of Pharmacology, Vol. 38, No. 4, July-August, 2006, pp. 289-290 Research Letter Effects of tamoxifen therapy on the endometrium in postmenopausal patients of breast cancer S. Gupta, V.R. Tandon, B. Kapoor, A. Gupta*, G.D. Gupta**, V. Khajuria Post Graduate Department of Pharmacology and
Therapeutics,
*Post Graduate Department of Radiotherapy and Oncology,
**Post Graduate Department of Radiodiagnosis and Imaging,
Govt. Medical College, Jammu–180001, (J&K). India
E-mail: dr_vishaltandon@yahoo.com Code Number: ph06077 Tamoxifen (TM) has been the mainstay of hormonal treatment in early, advanced and metastatic breast cancer. However, concerns have been raised about the oncogenic potential of TM due to its estrogen agonistic activity on the endometrium (EM), especially in postmenopausal (PM) women.[1] However, here too, many studies have failed to confirm an increase in the frequency of endometrial hyperplasia or carcinoma.[2], [3] Most reports regarding the effects of TM on the endometrium originate from outside India. Although one report is available from India,[4] overall there is a paucity of data regarding these effects on postmenopausal women in India. Therefore, the present observational study, over a period of one year, has been undertaken to assess the effects of TM on the endometrium in postoperative, postmenopausal patients of breast cancer. The study was approved by the Institutional Ethics Committee and written, informed consent was obtained. All patients were subjected to a detailed history, and clinical and gynaecological examination. Patients with normal routine laboratory tests and ECG were included in the study. Any patient with unexplained uterine bleeding, pre-existing endometrial cancer, diabetes mellitus, thyroid dysfunction or other endocrinopathies was excluded. Pre-menopausal patients, patients receiving other medications, concomitant chemotherapy, estrogenic hormones or those who had undergone hystrectomy or oophrectomy were also excluded from the study. The patients were given tablet tamoxifen 20mg (Dabur India Ltd.) daily for 9 months. Uterine EM was studied using ultrasonography (transabdominal-TA/transvaginal-TV). The study patients comprised two groups - new patients, who were PM patients of early stage breast cancer (T 3 N 1 M 0 ) and who were yet to be started on TM; and old patients, who were PM patients of early stage breast cancer (T 3 N 1 M 0 ) and who were already on TM for varied duration (up to 1 year,> 1-2,> 2-3,> 3-4,> 4-5 years). A total of 174 PM breast cancer patients participated in the study, of which 169 completed the study. Out of these, 35 were new and 134 were old patients. New PM patients were on treatment for 9 months and had to undergo 2 post registration visits on Day 0 and at the end of the ninth month. During these visits, the patients were subjected to ultrasonography (USG; TA/TV) examination, by the same observer. The choice of TA or TV (USG) was based on the preference of the patient. Once opted for, the treatment procedure was not changed. Old PM patients were also subjected to USG (TA/TV). Out of the total of 169, 95 patients preferred the TV approach. All patients with an endometrial thickness of more than 6mm on USG were considered abnormal[5] and subjected to histopathology of the endometrium. The results (mean±SEM) were analysed by paired-t-test for intra-group significance. The chi-square test was used for the data expressed in percentages. The correlation of endometrial thickness with the duration of TM exposure was analysed using the chi-square for linear trends. The mean endometrial thickness increased significantly in new patients after 9 months ( P < 0.001) from the base line. In the old patients, there was a significant association between endometrial thickness and duration of TM exposure. [Table - 1] A total of 41 patients (5 new and 36 old) had> 6mm endometrial thickness, of which biopsy was possible only in 35 patients. In 6 patients, endometrial biopsy was not possible due to cervical stenosis. However, they were given repeat USG (9 months) which showed no further change. A histopathological examination revealed changes as shown in [Table - 2]. No case of endometrial carcinoma was detected. Concerns have been raised about the oncogenic potential of TM due to its estrogenic activity on the endometrium, especially in postmenopausal women.[1] The incidence of endometrial cancer increases with exposure to estrogens. TM was found to cause a significant increase in endometrial thickness at 9 months, from baseline values, in new postmenopausal patients of breast cancer. Our findings are in agreement with the study of Bertelli, et al .[6] In old postmenopausal patients of breast cancer, who were already taking TM for varied duration of time (0-5 years), a trend of increase in endometrial thickness with increasing duration of TM exposure was observed. Such findings are in conformity with the findings of Love, et al .[3] The findings of the present study are also in accordance to a previous report from India, where there was a significant difference in the mean endometrial thickness between the study group and the control group. More women in the TM group had an endometrial thickness of> 5 mm, but the number of women with polyps or hyperplasia of the endometrium did not differ significantly between the two groups. There were no women with endometrial carcinoma in either group.[4] However, unlike our study, this study was a case control study which included only old and new patients on TM. They were compared with those not receiving TM. The mechanism of endometrial thickening is not yet fully understood. It could be due to the estrogenic effect of TM. USG can identify the endometrial thickness, but cannot differentiate between several endometrial pathologies, i.e., between endometrial polyps, atrophy or hyperplasia.[2] The present study also attempted to correlate USG findings with histopathology. Out of 35 patients subjected to histopathology, thickened endometrium could be explained only in 9 (25.71%) by endometrial polyps and simple cystic hyperplasia, while 18 (51.42%) had atrophic EM. This 51% false positive rate of USG is very high. Hence, several unnecessary endometrial biopsies may be performed. Mourits, et al [2] also recorded similar findings. Sonohysterography has been suggested, to monitor endometrial changes in women taking TM, for its better specificity with respect to the differentiation of uterine polyps from hyperplastic endometrium.[6] This study did not confirm an increased frequency of endometrial hyperplasia or carcinoma as reported by researchers in the past.[1] Our findings are consistent with the reports by Mourits, et al [2] and Love, et al [3] showing no TM induced increase of endometrial carcinoma. To conclude, the present study demonstrated that TM therapy causes an apparent increase of endometrial thickness as evidenced by ultrasound in new patients, whereas a positive correlation of endometrial thickness with duration of TM exposure was observed in the old patients. However, the results of endometrial biopsies did not confirm an increased frequency of endometrial hyperplasia or cancer. References
Copyright 2006 - Indian Journal of Pharmacology The following images related to this document are available:Photo images[ph06077t1.jpg] [ph06077t2.jpg] |
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