ENDOMETRIAL CANCER IN TAMOXIFEN-TREATED BREAST-CANCER PATIENTS - FINDINGS FROM THE NATIONAL SURGICAL ADJUVANT BREAST AND BOWEL PROJECT (NSABP) B-14

Background: Tamoxifen is advantageous in treating all stages of breast cancer. However, studies have suggested that incidence and severity o f endometrial cancer increase in women treated with tamoxifen. Purpose : We compared rates of endometrial and other cancers in tamoxifen- and non-tamoxifen-treated patients and described the pathologic character istics of the endometrial cancers. Methods: Data were analyzed on 2843 patients with node-negative, estrogen receptor-positive, invasive bre ast cancer randomly assigned to placebo or tamoxifen (20 mg/d) and on 1220 tamoxifen-treated patients registered in NSABP B-14 subsequent to randomization. Average time on study is 8 years for randomly assigned patients and 5 years for registered patients. Results: The incidence rates of liver, gastrointestinal, urinary tract, and nonuterine genita l tumors were not increased by tamoxifen treatment. Twenty-five endome trial cancers were originally reported. one of which was reclassified after subsequent review. Two cases occurred in the placebo group in pa tients whose medical status subsequent to random assignment had requir ed tamoxifen treatment. Twenty-three occurred in the tamoxifen groups. Twenty-one of the 24 originally reported endometrial cancers were FIG O stage 1; 18 of 23 gradable cases were of good to moderate histologic grade. Four tamoxifen-treated women died of uterine cancer. The avera ge annual hazard rate of endometrial cancer as a first event within th e first 5 years of follow-up in the randomized, tamoxifen-treated grou p was 1.2/1000 patient-years; the cumulative hazard rate was 6.3/1000. Findings for the registered, tamoxifen-treated group were similar. In cluding all originally reported endometrial cancers, the annual hazard rate through all follow-up was 0.2/1000 in the placebo group and 1.6/ 1000 in the randomized, tamoxifen-treated group; the relative risk of endometrial cancer for the latter versus the former group was 7.5. Aga in for the latter group, using population-based rates of endometrial c ancer from SEER data and information from another NSABP (B-06) trial, relative risks were 2.2 and 2.3, respectively. The 5-year cumulative h azard rate for disease-free survival in the randomized tamoxifen group was 38% less than that in the placebo group. Some data in this paper were provided by an investigator who submitted fraudulent data to the NSABP [see the ''News'' section]; therefore, the reader must read the entire text including Table 10 and the Editor's notes. In brief, data on 182 of the 2843 randomly assigned patients and 37 of the 1220 regis tered patients were provided by the investigator in question. After re view, 24 of the 182 records showed falsification, all involving charac teristics of patients prior to random assignment. Of the 37 registered -patient records, 8 showed falsification. Conclusions: Risk of endomet rial cancer increases following tamoxifen therapy for invasive breast cancer, however, net benefit greatly outweighs risk. Endometrial cance rs occurring after tamoxifen therapy do not appear to be of a differen t type with a worse prognosis than are such tumors in non-tamoxifen-tr eated patients. Implications: Tamoxifen treatment for breast cancer sh ould continue. In addition, the relative risk of endometrial cancer ob served in B-14 tamoxifen-treated patients is consistent with the twofo ld relative risk used in the initial risk-benefit computation for the NSABP breast cancer prevention trial.