Abstract P4-08-02: Importance of adverse events during endocrine treatment for the prediction of late distant recurrences
Authors: Sestak I , Dowsett M , Cuzick J 
Published: May 2019

Abstract
Background: During endocrine treatment of breast cancer, the occurrence of symptoms related to oestrogen depletion are important predictor of treatment efficacy. We have previously shown that appearance of vasomotor and joint related symptoms are a useful biomarker for a greater response to endocrine treatment (Cuzick et al., Lancet, 2008). Furthermore a prediction model including clinicopathological parameters (CTS5) has shown to be a good prognostic tool for the prediction of late distant recurrences (DR) (Dowsett et al., JCO, 2018). Here, we assessed whether the occurrence of endocrine related adverse events were predictive of late DR in the ATAC trial.
Methods: The ATAC trial (N=4735) of postmenopausal women with estrogen receptor positive breast cancer treated with 5 years' tamoxifen or anastrozole was used for this analysis. Women who reported symptoms (hot flashes, joint symptoms, gynaecological symptoms) at any time during the trial were compared to those not reporting these symptoms for late DR. Time to late DR, defined beginning at 5 years after randomization, was the primary endpoint. Hazard ratios (HR) and corresponding 95% CIs were estimated by Cox proportional hazards regression models.
Results: 2937 women (62%) who were recurrence free after 5 years, reported either hot flashes, joint symptoms, or gynaecological symptoms during the active treatment period. Women who reported joint symptoms (adjusted for CTS5: HR=0.74 (0.59-0.94)), or gynaecological symptoms (adjusted for CTS5: HR=0.68 (0.47-0.97)) had significantly fewer late DR compared to those not reporting these events during the active 5 years' treatment period. Those who reported any symptom during the treatment period had an overall 34% lower risk of a late DR (univariate: HR=0.66 (0.53-0.83), P&lt;0.001; adjusted for CTS5: HR=0.75 (0.60-0.93), P=0.009). The 5-10 year DR risk for women who reported any symptoms was 7.4% (6.4-8.5) compared to 11.0% (9.3-12.8) for those without symptoms. Women who reported any symptoms and who were randomized to either anastrozole (HR=0.67 (0.48-0.92)) or tamoxifen (HR=0.65 (0.48-0.88)) had significantly fewer late DR compared to those not reporting these symptoms. Women with symptoms on tamoxifen did have better 10-year DR risk compared to those without symptoms on anastrozole (8.1% (6.7-9.8) vs. 9.8% (7.7-12.4)).
Conclusions: This retrospective analysis of the ATAC trial showed that occurrences of endocrine related symptoms during the treatment period are associated with the risk of developing a late DR, irrespective of treatment allocation. Larger effects were found for joint or gynaecological symptoms and remained significant after adjustment for clinical parameters. These findings might help clinicians and patients in their decision making process about extended endocrine therapy.
Citation Format: Sestak I, Dowsett M, Cuzick J. Importance of adverse events during endocrine treatment for the prediction of late distant recurrences [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-02.