Comparison of uterine malignancies that develop during and following tamoxifen therapy

There is a greater than 7-fold increased risk of uterine cancer in women with breast cancer exposed to tamoxifen. The objective of this study was to determine the percentage of women who developed uterine cancer more than 12 months after discontinuing tamoxifen (past users) and to compare their clinical and pathologic features with those of women who developed uterine cancer while on tamoxifen therapy or within 12 months of stopping therapy (recent users).

All women with a diagnosis of uterine cancer at Memorial Sloan-Kettering Cancer Center between 1980 and June 2004 with a past history of breast cancer treated with tamoxifen were identified. Clinical and pathologic data were obtained through retrospective chart review.

There were 106 women identified with a history of breast cancer treated with tamoxifen preceding their diagnosis of uterine cancer. Thirty-nine (37%) developed uterine cancer more than 12 months after discontinuing tamoxifen. The median time until developing uterine cancer in past users was 33 months (range, 13-22). There were no significant differences in age at breast cancer diagnosis, body mass index, parity, stage of breast cancer, modality of breast cancer treatment, or duration of tamoxifen therapy between past and recent users of tamoxifen. Women who were past users of tamoxifen had significantly more FIGO (International Federation of Gynecology and Obstetrics) grade 3 and non-endometrioid histologic subtypes (P = 0.009; P = 0.007).

More than one third of women treated with tamoxifen develop uterine cancer more than 12 months after discontinuing therapy. These women are at greater risk of developing moderately to poorly differentiated tumors, which is a known poor prognostic factor. Therefore, women with a past history of tamoxifen therapy should have continued surveillance after completion of tamoxifen to ensure early diagnosis of uterine cancer.