Abstract GS2-02: 12 year results of anastrozole versus tamoxifen for the prevention of breast cancer in postmenopausal women with locally excised ductal carcinoma in-situ
Authors: Sestak Ivana , Cuzick Jack , Bonanni Bernardo , Bundred Nigel , Levy Christelle , Loib Sibylle , Neven Patrick , Stierer Michael , Holcombe Chris , Coleman Robert , Forbes John , Howell Anthony 
Published: February 2021

Background: Two large clinical trials have reported divergent results in their initial analysis of the benefit of aromatase inhibitors compared to tamoxifen in women with ductal carcinoma in situ (DCIS) (IBIS-II and NSABP B-35). Here, we report blinded 12-year median follow-up efficacy and adverse event data for the IBIS-II trial, which compared anastrozole to tamoxifen in women with hormone receptor positive DCIS and focus on the post-treatment follow-up period.Methods: A multi-centre randomised trial of 1mg/day anastrozole (N=1471) vs. 20mg/day tamoxifen (N=1509) for five years was conducted in postmenopausal women with locally excised DCIS diagnosed between 2003 and 2009. The primary objective of this analysis was to determine the efficacy of anastrozole compared to tamoxifen in preventing recurrences overall, and in particular in the post 5-year treatment period. Secondary endpoints included type of recurrence, breast cancer mortality, other cancers, cardiovascular disease, fractures, adverse events and non-breast cancer deaths.Results: After a median follow-up of 11.6 years (IQR 9.9 to 13.4), a total of 221 breast cancer recurrences (7.4%) have been recorded. No difference in overall recurrence was observed (102 (6.9%) anastrozole vs. 119 (7.9%) tamoxifen; HR=0.87 (0.67-1.14), P=0.32) overall (Table), in the 5-year treatment period (HR=0.82 (0.53-1.27), P=0.37), or the post treatment follow-up period (HR=0.91 (0.65-1.27), P=0.57). Oestrogen receptor (ER) positive breast cancers were reduced by 28% with anastrozole when compared to tamoxifen (58 vs. 82; HR=0.72 (0.52-1.01), P=0.056) but this did not reach significance. In contrast, no effect was observed for ER-negative breast cancer with anastrozole (Table). No significant difference for the reduction in invasive breast cancer recurrence was observed with anastrozole when compared to tamoxifen (Table). Invasive ER-positive breast cancer was non-significantly reduced by 24% with anastrozole when compared to tamoxifen (44 vs. 59; HR=0.76 (0.51-1.12), P=0.17). A total of 127 deaths have been reported, with no significant difference in all-cause mortality between the two treatment arms (61 vs. 66; HR=0.94 (0.67-1.33), P=0.74). Only 7 deaths from breast cancer (3 vs. 4) were reported, with so few deaths from breast cancer at 12 years, any impact on survival is unlikely to emerge with longer follow-up. 214 cancers other than breast were reported, with a non-significant decrease observed with anastrozole (97 vs. 117, OR=0.84 (0.63-1.12), P=0.22). Endometrial (2 vs. 13, OR=0.16 (0.02-0.0.69)), ovarian cancer (1 vs. 9, OR=0.11 (0.003-0.82)), and non-melanoma skin cancer (11 vs. 21) were less common with anastrozole. Significantly higher rates of fractures (181 vs. 145, OR=1.32 (1.04-1.68)) and transient ischaemic attacks (15 vs. 5, OR=3.10 (1.07-10.92)) were observed with anastrozole compared to tamoxifen. A comprehensive adverse event profile will be reported.

Conclusions: No clear efficacy differences were seen between the two treatments, although the data suggests possible greater efficacy for anastrozole over tamoxifen for prevention of ER-positive breast cancers. There were some clear differences in adverse events and anastrozole may be more appropriate for some women with contraindications for tamoxifen.

Table: Number of events and Hazard Ratios (95% CI) according to treatment allocation.Anastrozole(N=1471)Tamoxifen(N=1509)HR (95% CI)Any recurrence1021190.87 (0.67-1.14)ER-positive58820.72 (0.52-1.01)ER-negative24151.63 (0.86-3.11)Invasive66760.89 (0.64-1.23)ER-positive44590.76 (0.51-1.12)ER-negative17121.44 (0.69-3.02)DCIS35420.85 (0.54-1.33)ER-positive14230.62 (0.32-1.21)ER-negative732.38 (0.61-9.20)Numbers do not add up due to missing information

Citation Format: Ivana Sestak, Jack Cuzick, Bernardo Bonanni, Nigel Bundred, Christelle Levy, Sibylle Loib, Patrick Neven, Michael Stierer, Chris Holcombe, Robert Coleman, John Forbes, Anthony Howell. 12 year results of anastrozole versus tamoxifen for the prevention of breast cancer in postmenopausal women with locally excised ductal carcinoma in-situ [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-02.