Abstract P3-07-06: Comedications at Breast Cancer diagnosis impact overall survival: results from the ADRENALINE (Atlas for DRug and brEast caNcer survivAL INtEraction) study (n=235,368)
Authors: Dumas Elise , Grandal Beatriz , Gougis Paul , Houzard Sophie , Latouche Aurélien , Toussaint Aullène , Alsafadi Samar , Abecassis Judith , Delrieu Lidia , Dubois Thierry , Sella Nadir , Espie Marc , Asselain Bernard , Ballesta Annabelle , Marande Benjamin , Daoud Eric , Laas Enora , Kassara Amyn , Jochum Floriane , Nery Elaine Del , Anthony Elodie , Le Bihan-Benjamin Christine , Bousquet Philippe-Jean , Azencott Chloé-Agathe , Reyal Fabien , Hamy Anne-Sophie 
Published: March 2023

Abstract
Background: More than half of Breast Cancer (BC) patients take chronically used non-cancer treatments (denoted as comedications) at BC diagnosis. Epidemiological evidence has reported that several non-cancer treatments may modify BC risk, BC recurrence, and overall survival (OS). The ADRENALINE project (Atlas for DRug and brEast caNcer survivAL INtEraction) analyses the impact of the use of each commonly prescribed non-cancer treatment at BC diagnosis on OS using the French social security system data on a comprehensive cohort of French BC patients. Methods: We identified all women diagnosed with an incident BC treated with surgery in France from 2011 to 2017 and affiliated to the general health insurance scheme. Women with concomitant cancer or metastases at diagnosis were discarded from the analyses. Comedication intake was defined as the delivery in pharmacy of at least 3 months of full treatment (e.g. 90 pills) the 6 months preceding BC diagnosis. A Cox proportional hazard model was used to estimate the hazard ratio (HR) for each molecule. The model was adjusted on more than 100 confounding variables: social factors, comorbidities and other comedications by Inverse Probability of Treatment Weighting (IPTW). We assumed that the adjustment was sufficient to control for confounding if the standardized mean difference of each confounder after adjustment did not exceed 0.1. Molecules which did not pass the adjustment quality test were discarded. Results: Overall, 235,368 patients were included in the study. Among 219 selected drugs, 91 passed the adjustment quality test. The full set of results is available on a web application (https://adrenaline.curie.fr). Several drugs or drug classes were associated with an improved survival: statins (e.g. rosuvastatin, HR=0.65, p&lt; 0.001); proton-pump inhibitors (HR=0.93; p=0.002); or beta-blocking agents (atenolol, HR=0.78, p=0.003). Conversely, anti-anemic preparations (folic acid and ferrous sulfate) had a significant deleterious effect (HR = 1.63; p&lt; 0.001). Drugs from the same therapeutic class, could have different effects: within benzodiazepines, bromazepam was protective (HR = 0.91; p = 0.038) while oxazepam was deleterious (HR = 1.37; p &lt; 0.001). Conclusion: ADRENALINE reports the impact on BC survival of 219 widely prescribed drugs. It can be used to identify molecules with a potential protective or deleterious effect relative to BC. Some of them are currently under mechanistical investigation within a drug screening program. This atlas highlights candidates to drug-repurposing trials or pharmacovigilance warnings, and will be extended to cancers of other localizations in a near future.
Citation Format: Elise Dumas, Beatriz Grandal, Paul Gougis, Sophie Houzard, Aurélien Latouche, Aullène Toussaint, Samar Alsafadi, Judith Abecassis, Lidia Delrieu, Thierry Dubois, Nadir Sella, Marc Espie, Bernard Asselain, Annabelle Ballesta, Benjamin Marande, Eric Daoud, Enora Laas, Amyn Kassara, Floriane Jochum, Elaine Del Nery, Elodie Anthony, Christine Le Bihan-Benjamin, Philippe-Jean Bousquet, Chloé-Agathe Azencott, Fabien Reyal, Anne-Sophie Hamy. Comedications at Breast Cancer diagnosis impact overall survival: results from the ADRENALINE (Atlas for DRug and brEast caNcer survivAL INtEraction) study (n=235,368) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-06.