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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< 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< 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 < 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.

Background: Cancer caused nearly 10 million deaths in 2020. While most of the ongoing research focuses on finding new treatments, accessibility to oncology care receives less attention. However, access to health services plays a key role in cancer survival. Spatial accessibility methods have been successfully applied to measure accessibility to primary care. Yet, little research to date focused on oncology care specifically. Methods: We focused on all care centers with medicine, surgery, or obstetric activity in metropolitan France. We propose a clustering algorithm to automatically label the hospitals in terms of oncology specialization. Then, we computed an accessibility score to these hospitals for every municipality in metropolitan France. Finally, we proposed an optimization algorithm to increase the oncology accessibility by identifying centers which should increase their capacity. Results: We labelled 1,662 care centers into 8 clusters. Half of them were eligible for oncology care and 118 centers were identified as experts. We computed the oncology accessibility score for 34,877 municipalities in metropolitan France. Half of the population lived in the top 20% accessibility areas, and 6.3% in the bottom 20% zones. Accessibility was higher near dense cities, where the experts care centers were located. By combining the care centers clusters and the accessibility distributions, our optimization algorithm could identify hospitals to grow, to reduce accessibility disparities. Conclusion: Our method made it possible to quantify oncology care accessibility across all metropolitan France, as well as to make suggestions on where to increase hospital capacity to improve accessibility, especially in more populated suburban areas. Our approach was deliberately non-specific to cancer type nor to the kind of stays, but it could be adapted to more specific scenarios. We packaged our method into a web application allowing the users to run the algorithms with various parameters and visualize the results. Citation Format: Eric Daoud, Anne-Sophie Hamy, Elise Dumas, Lidia Delrieu, Beatriz Grandal, Christine Le Bihan-Benjamin, Sophie Houzard, Philippe-Jean Bousquet, Judicael Hotton, Aude-Marie Savoye, Christelle Jouannaud, Chloé-Agathe Azencott, Marc Lelarge, Reyal Fabien. Disparities in accessibility to oncology care centers in France [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1022.

Background: Breast cancer (BC) incidence increases with age, as well as the incidence of many other chronic diseases. Between 42 and 68% of BC patients suffer from other chronic conditions -comorbidities- at BC diagnosis. Comorbidities may be associated with the intake of chronic medications -comedications. The French health insurance system routinely collects health care reimbursements of almost 98% of the population: hospital abstracts, long-term diseases, outpatient care (medical consults, drug purchases under prescription⋯) and death status. The project ADRENALINE (Atlas for DRug and brEast caNcer survivAL INtEraction) analyzes the impact of comedications at diagnosis on BC survival on a French cohort using data from the French social security system. 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. The analysis was restricted to drugs taken by at least 300 women. 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. Two adjustment methods were tested: Inverse Probability of Treatment Weighting (IPTW) and matching. 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: 235,375 patients were included in the study. Among 219 selected drugs, 91 and 171 passed the adjustment quality test for IPTW and for matching, respectively. The full set of results is available on a web application. Among main findings, several drugs or drug classes were associated with an improved survival: proton-pump inhibitors (IPTW; HR=0.93; p=0.002); statins (e.g. rosuvastatin, IPTW, HR=0.65, p 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, Lucie Laot, Eric Daoud, Lidia Delrieu, Marc Espié, Sophie Houzard, Christine Le Bihan-Benjamin, Philippe-Jean Bousquet, Elodie Anthony, Aurélien Latouche, Nadir Sella, Thierry Dubois, Annabelle Ballesta, Amyn Kassara, Elaine Del Nery, Benjamin Marande, Samar Alsafadi, Paul Gougis, Chloé-Agathe Azencott, Fabien Reyal, Anne-Sophie Hamy. ADRENALINE, an atlas for drug and breast cancer survival interaction: Comedications at diagnosis and impact on breast cancer mortality of the French breast cancer cohort (n=235,375) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4101.