Abstract P5-12-10: Comparison of the efficacy of tamoxifen and aromatase inhibitors on survival in adjuvant menopausal breast cancer
Authors: Chay WY , Speers C , Gondara L , Tyldesley S , Ellard SL , Lohrisch CA , Gelmon KA 
Published: May 2016

Background

Meta-analyses of postmenopausal endocrine therapy and recent studies in premenopausal women suggest that aromatase inhibitors (AI) may be superior to tamoxifen (T) in preventing recurrence in early hormone receptor positive (HR+) breast cancer (BC), although there are recent concerns about the impact on overall survival (OS). The BC Cancer Agency adopted ASCO guidelines of an AI as part of adjuvant therapy for menopausal HR+ BC in 2003. Using our population based data, we sought to compare the 10 year survival outcomes for patients starting either T or AI following surgery for HR+BC.

Methods

Histopathologic and demographic data were collected for all menopausal patients referred to the BC Cancer Agency with a T1-2, node negative, HR+, HER2 negative BC diagnosed between 01/2003 and 12/2009. Patients with prior or synchronous contralateral BC were excluded. Data was cross-referenced to the provincial pharmacy database, which tracks hormone therapy. Significant factors affecting survival were identified using Cox proportional hazard model for OS and Fine and Gray's (FG) model for BC specific and Cardiac Specific Survival (CSS) with causes other than event of interest defined as competing.

Results

We identified a cohort of 3421 cases with median follow up of 7.8 years (y) for T and 7.4 y for AI. Median age was 65y in both groups, and 8.5% received chemotherapy. 47.8% of tumors were T1c and 22.2% were T2; 15.8 % were grade 3. 10 year OS was 84.4% (95% Confidence Intervals [CI] 82.4%, 86.2%) and 82.7% (95% CI 79.4%, 85.6%) for T and AI cohorts, respectively, (p= 0.02). BCSS did not differ between the groups (p=0.54). We categorized causes of death in each cohort as from BC (20.4% T, 20.6% AI), other cancers (25.4% T, 22.1% AI), cardiovascular-related (CVS) (25.8% T, 34.6% AI), thromboembolic (0.3% T, 0.7% AI %) and other (25.4%T, 19.1 % AI). Table 1 shows Univariate (U), multivariable (M), hazard ratios (Hz) and 95% CI.

Table 1 OSBCSSCSS UM (KM)UM ( FG)UM  Hz Hz HzTumour Size, continuous&lt;0.0001&lt;0.0001&lt;0.0001&lt;0.0001&lt;0.00010.0280  1.282 (1.142,1.438) 1.882 (0.631,2.090) 1.272 (1.026, 1.577)Age at dx,continuous&lt;0.0001&lt;0.00010.00190.2637&lt;0.0001&lt;0.0001  1.094 (1.080,1.108) 1.016 (0.988,1.044) 1.152 (1.122,1.183)Grade , 3 vs 1&lt;0.00010.0557&lt;0.00010.00180.29930.8719  1.341 (0.993,1.811) 2.973 (1.501,5.889) 1.051 (0.576,1.915)LVI, Yes vs No0.00040.0465&lt;0.00010.00010.24870.0671  1.357 (1.005,1.833) 2.732 (1.637,4.558) 0.474, (0.213,1.054)Chemo use, Yes or No0.0990.21220.05350.50290.02050.8710  0.748 (0.474,1.180) 1.284 (0.618,2.670) 1.128 (0.264,4.824)AI vs T0.020.29270.59250.25540.00410.0123  1.124 (1.142,1.438) 0.742 (0.443,1.241) 1.658 (1.116,2.463)

Conclusion

While trials show that AIs improve relapse free survival after menopausal HR+BC, their impact on BCSS has been minimal. By contrast they may contribute to CVS deaths, as suggested by our data. We plan to explore this observation further by examining baseline cardiac risk factors within our T and AI cohorts, and by exploring OS, BCSS, and CSS among patients switching to AI after starting T, to identify the optimal adjuvant hormone therapy strategy for menopausal women with HR+ early BC.

Citation Format: Chay WY, Speers C, Gondara L, Tyldesley S, Ellard SL, Lohrisch CA, Gelmon KA. Comparison of the efficacy of tamoxifen and aromatase inhibitors on survival in adjuvant menopausal breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-10.