Abstract PO3-11-07: Dose-response association between post-diagnosis exercise and clinical outcomes among survivors of breast cancer (BC)
Authors: Soldato Davide , Luis Ines Vaz , Havas Julie , Meglio Antonio Di , Iyengar Neil , Pistilli Barbara , Cottu Paul , Lerebours Florence , Coutant Charles , Bertaut Aurélie , Trédan Olivier , Vanlemmens Laurence , Jouannaud Christelle , Hrab Ioana , Everhard Sibille , Martin Anne-Laure , André Fabrice , Jones Lee 
Published: May 2024

Abstract
Background: Higher levels of pre and post-diagnosis physical exercise lead to reduced risk of death among survivors of BC. However, the effect of exercise on recurrence remains unclear. Furthermore, previous studies assumed a linear relationship between exercise and clinical outcomes, used discrete classifications of exercise and did not report results according to BC subtype. The aim of this study was to investigate the dose–response relationship of exercise and clinical outcomes among survivors of BC and by BC subtypes.
Methods: We included pts diagnosed with stage I-III BC from the CANTO cohort (NCT01993498). CANTO collects longitudinal data, including self-reported exercise exposure using the Global Physical Activity Questionnaire (GPAQ-16), at diagnosis (dx), 1 (T1), 2 (T2) and 4 (T3) years after dx. Exercise exposure in travel and leisure time was calculated according to GPAQ16 guidelines to derive a total MET-hours per week (MET-h/w) at dx and T1 and absolute change in exercise was computed between these timepoints. Outcome of interest was distant relapse-free interval (DRFI) according to STEEP criteria. Restricted cubic splines from unadjusted Cox models assessed the dose-response relationship between exercise and DRFI in the overall cohort and by BC subtype. Kaplan-Meier estimator, log-rank test and multivariate Cox models assessed the prognostic role of exercise.
Results: In the overall cohort with available data on exercise at dx (N=10,359) mean (SD) age and BMI were 56.3 (11.2) years and 25.9 (5.4) kg/m2, 38.7% of pts were premenopausal, 52.9% received chemotherapy and 81.9% hormonal therapy, 57.1% were meeting WHO exercise recommendations at dx. At a median (IQR) follow-up of 5.5 (3.9-6.5) years, 541 DRFI events were observed. In the overall cohort, the spline showed a significant non-linear relationship between exercise at dx and DRFI: exposure greater than ≈5 MET-h/w was associated with an inverse linear risk reduction up to ≈25 MET-h/w. A similar relationship was observed in the HR+/HER2- and HR-/HER2- cohorts. On this basis, exercise was categorized as ‘no exercise’ (0 MET-h/w) and ‘exercise’ (≥ 5 MET-h/w). Pts reporting exercise ≥ 5 MET-h/w had longer DRFI compared to those reporting no exercise in the overall (log-rank p&lt; 0.0001), HR+/HER2- (log-rank p&lt; 0.0113) and HR-/HER2- (log-rank p&lt; 0.0001) cohorts. In multivariate analyses, reporting exercise ≥ 5 MET-h/w was associated with a significant lower risk of DRFI events in the overall (HR 0.75, 95%CI 0.62-0.90) and HR-/HER2- cohorts (HR 0.54, 95%CI 0.37-0.80). Absolute change in exercise exposure from dx to T1 was available in 8,516 pts: 34.2% increased exercise (≥ 5 MET-h/w), 25.9% decreased exercise (≤ -5 MET-h/w) and 39.8% maintained exercise ( &gt; –5 and &lt; +5 MET-h/w). The spline showed a non-significant relationship between change in exercise and risk of DRFI events and change in exercise was not significantly associated with risk of DRFI events in multivariate analyses.
Conclusions: In this large, prospective cohort of survivors of BC, higher exercise at diagnosis was associated with reduced risk of DRFI events. The relationship between exercise dose and clinical outcomes appears non-linear and to differ based on subtype. Change in exercise after breast cancer diagnosis does not appear to impact on clinical outcomes. Future studies should aim at validating these findings in independent cohorts.
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Citation Format: Davide Soldato, Ines Vaz Luis, Julie Havas, Antonio Di Meglio, Neil Iyengar, Barbara Pistilli, Paul Cottu, Florence Lerebours, Charles Coutant, Aurélie Bertaut, Olivier Trédan, Laurence Vanlemmens, Christelle Jouannaud, Ioana Hrab, Sibille Everhard, Anne-Laure Martin, Fabrice André, Lee Jones. Dose-response association between post-diagnosis exercise and clinical outcomes among survivors of breast cancer (BC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-07.