Temporal Relationships between Tamoxifen Use and Endometrial Malignancies.
Deborah DeLair, Sarah Ferguson, Robert Soslow, Karuna Garg. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: The development of uterine malignancies during and after the use of tamoxifen is a well-documented phenomenon. The purpose of the study was to determine if there was a correlation between the duration of tamoxifen therapy, the development of these malignancies in relation to cessation of the drug, and tumor type and/or grade. In addition, we sought to determine any recurrent morphologic features present in these tumors.
Design: All women with a history of breast cancer treated with tamoxifen who subsequently developed a uterine malignancy between 1980 and 2005 were included in the study.
Results: A total of 119 such patients were identified. The distribution of tumor type was as follows: 64 FIGO 1-2 endometrioid carcinomas (EC), 7 FIGO 3 endometrioid carcinomas, 28 serous carcinomas or mixed endometrioid and serous carcinomas, 3 clear cell carcinomas, 2 undifferentiated carcinomas, 13 carcinosarcomas (MMMT) and 2 leiomyosarcomas. There was a higher incidence of high grade tumors in patients who received tamoxifen for 5 years or more (59%), compared to those who used tamoxifen for less than 5 years (26%). Low grade tumors also appear to develop more frequently early on after the use of tamoxifen; the frequency of high grade tumors was more in cases where the interval between cessation of tamoxifen therapy and diagnosis of endometrial carcinoma was more than 1 year (58%) compared to less than 1 year (38%). In the slides available for review, a number of recurrent morphologic features were noted including prominent squamous/morular metaplasia, background polyps and/or polypoid tumors, background endometrial atrophy (also seen in endometrioid tumors) and presence of prominent ovarian stromal hyperplasia.
|FIGO 1-2 EC||FIGO 3 EC||Serous||MMMT||Others|
|Tamoxifen therapy duration ≥5 years||30||6||24||10||3|
|Tamoxifen therapy duration <5 years||33||1||5||3||4|
|Interval between tamoxifen cessation and EC Less than 1 year||44||2||13||8||5|
|Interval between tamoxifen cessation and EC 1 year and more||19||4||1||5||2|