Abstract P2-09-16: How population-based data complement trial data in the adjuvant endocrine treatment of ER+/HER2+ breast cancers
Authors: Dackus GMHE , Jozwiak K , Sonke GS , Van der Wall E , Van Diest PJ , Hauptmann M , Siesling S , Linn SC 
Published: March 2017

Abstract
Background
This study is part of the Netherlands Breast Cancer Project, initiated to address research questions that are unlikely answered by future randomized controlled trials (RCT). Here we investigated whether aromatase inhibitors (AI) are superior over tamoxifen (TAM), in the treatment of Estrogen Receptor (ER) positive Human Epidermal growth factor Receptor 2 (HER2) positive breast cancer, using treatment and outcome data from the population based Netherlands Cancer Registry (NCR). RCTs showed superiority of AI over TAM in postmenopausal ER+/HER2+ patients while a (non-significant) suggestion for worse outcome was observed among premenopausal patients treated with AI in the SOFT/TEXT trial. Perimenopausal women were not considered in these trials.
Methods
Dutch women without a prior malignancy, diagnosed between 2005-2007 with an ER+/HER2+, endocrine treated, non-metastatic, invasive breast cancer, were identified through the NCR and followed until 2013. Since data on menopausal status were lacking, we used age at diagnosis as a proxy to categorize patients as premenopausal (≤45 years), perimenopausal (45-55 years) and postmenopausal (&gt;55 years). A time-dependent variable was calculated indicating whether AI treatment was given for &gt;50% (denoted AI treated) vs. &lt;50% (denoted TAM treated) of endocrine treatment duration. Recurrence-free survival (RFS) and overall survival (OS) were assessed using an extended Kaplan-Meier survival estimator and Cox proportional hazards regression. Hazard Ratios (HR) for the TAM/AI comparison, were adjusted for chemotherapy, trastuzumab, age at diagnosis, lymph node status, grade, clinical T stage, and ovarian ablation.
Results
We included 1158 patients: 326 pre-, 306 peri- and 526 postmenopausal. Of these, 229 received TAM and 929 AI. During follow-up, 239 RFS and 184 OS events were observed. In the TAM treated group, 56 RFS and 45 OS events were observed, in the AI treated group 183 RFS and 139 RFS events were observed respectively.
No differences in RFS were observed comparing AI to TAM treated patients in the premenopausal (HR 1.33; 95% CI 0.71-2.49; P=0.378) and postmenopausal (HR 0.84, 95%CI 0.54-1.32; P=0.456) group. However, perimenopausal patients benefitted significantly from AI compared with TAM (HR 0.50; 95% CI 0.27-0.95). Results were similar for OS: no significant benefit from AI when compared to TAM in pre- (HR 1.41; 95% CI 0.62-3.19; P=0.408) and postmenopausal (HR 0.75; 95% CI 0.47-1.22; P=0.245) patients while perimenopausal patients derived significant benefit from AI treatment (HR 0.42; 95% CI 0.20-0.85; P=0.016).
Conclusion
In this population based cohort study we observed superiority for AI over TAM in the treatment of ER+/HER2+ perimenopausal patients. Data were suggestive in favor of AI when compared to TAM for postmenopausal patients while an indication of worse outcome with AI was seen in premenopausal patients, consistent with results of the SOFT/TEXT trial. Although we used age as a proxy for menopausal status, our results are consistent with previous RCTs. Population based data may therefore provide a reliable source of information when new RCTs might not be feasible anymore.
Citation Format: Dackus GMHE, Jozwiak K, Sonke GS, Van der Wall E, Van Diest PJ, Hauptmann M, Siesling S, Linn SC. How population-based data complement trial data in the adjuvant endocrine treatment of ER+/HER2+ breast cancers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-09-16.