DESCRIPTIVE CLINICOPATHOLOGICAL STUDY OF 17 PATIENTS WITH ENDOMETRIALCANCER DURING OR AFTER ADJUVANT TAMOXIFEN IN EARLY BREAST-CANCER

Background: Studies have shown that patients with early-stage endometr ial cancer who have previously used endogenous estrogen (oral contrace ptives or estrogen replacement therapy) have a favorable prognosis. Th is has not yet been demonstrated for patients with early-stage endomet rial cancer who have received tamoxifen. In addition, studies have rai sed the question of whether women receiving tamoxifen are at increased risk of endometrial cancer. Purpose: Our aim was to determine whether the prognosis is favorable for patients with diagnosis of endometrial cancer after adjuvant treatment with tamoxifen for breast cancer. Met hods: We matched 931 patients from the Stockholm Adjuvant Tamoxifen Tr ial in early breast cancer against the Swedish Cancer Registry and ide ntified 17 who subsequently had endometrial cancer. These patients had been randomly assigned to receive 40 mg/d tamoxifen orally for 2 year s beginning 4 weeks after surgery for breast cancer. Histologic specim ens, patient records, and death certificates were reviewed to verify t reatment and causes of death. Results: Thirteen of the 17 patients dia gnosed with endometrial cancer were alive; for three of the four who h ad died, the cause of death was endometrial cancer. All 16 evaluable t umors except one were World Health Organization (WHO) histologic grade s I-II. Only one patient had advanced disease (stage IV); the remainin g tumor was a mixed mesodermal malignant tumor that could not be class ified under the WHO grading system. Median time for adjuvant tamoxifen use was 24 months (range, 6-60 months) with a median cumulative tamox ifen dose of 29 g (range, 7-72 g). Median time from initiation of adju vant tamoxifen to diagnosis of endometrial cancer was 32 months (range , 6-130 months). Ten-year actuarial survival after diagnosis of endome trial cancer for the 17 patients treated with tamoxifen was 73%. Concl usion: Because of the small number of patients, our results do not rul e out the possibility of a favorable prognosis for patients with a dia gnosis of endometrial cancer following tamoxifen treatment. Implicatio ns: The incidence of secondary endometrial cancer reported in this stu dy following treatment of breast cancer patients with tamoxifen at dos es of 40 mg/d in a large clinical trial is higher than that reported f or previous large trials of tamoxifen at doses of 20 mg/d. Thus, tamox ifen dosage may be a critical factor in the subsequent occurrence of e ndometrial cancer. Our results also suggest two important consideratio ns for improved follow-up in long-term tamoxifen trials: careful regis tration of second cancers and routine gynecologic examinations to ensu re early detection of endometrial cancer.