Dose-dependent effect of tamoxifen therapy on endometrial pathologies in postmenopausal breast cancer patients

To assess whether a higher cumulative tamoxifen dose is associated with inc reased incidence of various types of endometrial pathologies, we compared c umulative dose of tamoxifen treatment as well as demographic characteristic s, risk factors for endometrial cancer, transvaginal ultrasonographic endom etrial thickness, and various treatments for the primary breast cancer betw een 159 postmenopausal breast cancer tamoxifen-treated patients without end ometrial pathologies (group I) and 67 similar patients with endometrial pat hologies (group II). A similar comparison was made between group I patients and similar patients with proliferative endometrium (group IIa), with endo metrial hyperplasia (group IIb), with endometrial polyps (group IIc), and w ith endometrial cancer (group IId). Overall cumulative tamoxifen dose was s ignificantly higher in group II as compared to group I (27.4 +/- 33.4 and 1 7.4 +/- 20.2, respectively; P < 0.0252). Transvaginal ultrasonographic endo metrial thickness was significantly higher in group II than in group I pati ents (16.3 +/- 11.3 mm and 12.1 +/- 6.3 mm, respectively; P < 0.0147). The frequency of diabetes mellitus, of previous postmenopausal bleeding, and of previous exposure to hormone replacement therapy was significantly higher in group II than in group I patients (P < 0.001; P < 0.0001 and P < 0.001, respectively). There were no significant differences in all parameters test ed between group I, group IIa, group IIb, group IIc, and group IId. However , there was an obvious trend for higher cumulative tamoxifen dose in patien ts with benign endometrial pathologies as compared to those without endomet rial pathologies or to those with endometrial cancer (Group I = 17.4 +/- 20 .2 g, group IIa = 22.5 +/- 18.5 g, group IIb = 28.1 +/- 20.3 g, group IIc = 31.4 +/- 42.7 g and group IId = 10.4 +/- 12.6 g). Endometrial pathologies, except for endometrial cancer, are associated with a high cumulative dose of tamoxifen in postmenopausal breast cancer patients.