Abstract S3-07: 16 year long-term follow-up of the IBIS-I breast cancer prevention trial

Abstract

Abstract Background: Several randomised clinical trials have shown the benefit of tamoxifen in healthy women to reduce their risk of breast cancer. Here, we report the blinded median 16 year follow-up of the IBIS-I trial to update the long-term prevention of breast cancer with tamoxifen treatment. Methods: 7154 pre- and postmenopausal women were randomised to receive daily 20mg tamoxifen (N=3579) or matching placebo (N=3575) for 5 years. The primary endpoint of this analysis was the occurrence of breast cancer (invasive and ductal carcinoma in situ (DCIS)). Secondary endpoints included overall mortality, other cancers, and breast cancer specific mortality. Cox proportional hazard models were used to assess occurrence of breast cancer and survival. All statistical tests were two-sided. Results: After a median of 16.2 years (IQR 14.4 to 17.7) of follow-up, a total of 589 breast cancers have been reported (tamoxifen: 246 (6.9%) vs. placebo: 343 (9.6%)). Tamoxifen reduced the incidence of all breast cancer overall by 29% (HR=0.71 (0.60-0.83), P<0.0001) (Figure 1). Invasive ER-positive (ER+) breast cancers were reduced by 35% (HR=0.65 (0.53-0.80), P<0.0001) (Figure 1), but no effect was seen for invasive ER-negative (ER-) breast cancers (HR=1.06 (0.71-1.58), P=0.8). A non-significant 30% reduction in DCIS was seen with tamoxifen (36 vs. 51, HR=0.70 (0.46-1.07); P=0.1). The overall risk reduction was similar in years 0-10 (HR=0.71) and years 10-20 (HR=0.70). Similar effects were seen in pre- and postmenopausal women (HR 0.71 vs. 0.71). All-cause mortality was non-significantly increased in women randomised to tamoxifen (173 vs. 158, OR=1.10 (0.88-1.38), P=0.4). The excess in deaths with tamoxifen is smaller than in the 96 month update. No differences in breast cancer mortality was seen (24 tamoxifen vs. 27 placebo; OR=0.89 (0.49-1.60), P=0.7). A non-significant increase in other cancers than breast were reported by women on tamoxifen (350 vs. 315, OR=1.12 (0.95-1.32); P=0.2). Specifically more endometrial cancers (28 vs. 17), non-melanoma skin cancers (108 vs. 85), and lung cancer (32 vs. 20) were found in those randomised to tamoxifen. Conclusion: This updated analysis of the IBIS-I trial confirms the significant reduction in breast cancer occurrence with tamoxifen in the post-treatment follow-up period. These results indicate tamoxifen has a long-term preventive effect on invasive ER+ breast cancer in both pre- and postmenopausal women. Citation Format: Jack Cuzick, Ivana Sestak, Simon Cawthorn, Hisham Hamed, Kaija Holli, Anthony Howell, John F Forbes. 16 year long-term follow-up of the IBIS-I breast cancer prevention trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S3-07.