Background: It is estimated that 50 thousand patients live with metastatic breast cancer (MBC) in Brazil. A recent Brazilian registry (LACOG 0312) on MBC demonstrated a median overall survival (OS) by breast subtype of 15 months for triple negative, 23 months for HER2 positive, and 42 months for Luminal tumors, which are very similar to developed countries except the HER2 positive group which have limited access to targeted agents in the public health system. Recently, CDK 4/6 inhibitors were approved for the treatment of HR+ HER2-negative MBC with an improvement in progression-free survival (PFS) and ribociclib and abemaciclib demonstrating benefit in OS over endocrine therapy alone, establishing the standard of care in first-line setting for this BC subtype. In Brazil, disparities exist in the incorporation of novel anticancer agents between public and private health systems limiting treatment options for patients with HR+ HER2- negative MBC in the public system, which covers most of the population. The BRAVE study aims to describe the patient journey and current patterns of care for HR+ HER2-negative MBC to identify possible gaps and how health insurance type influences treatment patterns in Brazil. Trial Design: This is an observational, retrospective cohort study. All patients diagnosed with mBC (either de novo or recurrent) in the period of January 2018 to December 2020 at participating centers will be included. Data will be collected from medical records. No interventions are proposed. Enrollment of a total of 300 patients (150 patients from public health care system and 150 patients from private health care system) is planned. ClinicalTrials.gov identifier: NCT05034393. Eligibility: Inclusion criteria: women ≥18 years old; histologically confirmed HR-positive HER2-negative invasive breast cancer; HR-positive, defined as 1% to 100% of tumor nuclei positive for ER and/or PgR as per ASCO/CAP Guideline 2020 or Allred score of ≥3; HER2-negative, defined as IHC result is 0/1+ or 2+ with ISH negative as per ASCO/CAP Guideline 2018; diagnosed with de novo or recurrent metastatic breast cancer between January 2018 and December 2020. Exclusion criteria: male BC; first-line treatment for mBC received through clinical trial. Specific Aims: Primary objective is to describe the first-line (1L) treatment of HR-positive, HER2-negative mBC in Brazil. Secondary objectives are to describe progression-free survival (PFS) in the 1L setting until month 24; describe and compare the 1L treatment of HR-positive, HER2-negative mBC and PFS until month 24 according to the health care coverage (public vs. private); describe timelines from symptoms, histopathological diagnosis, molecular test, and treatment; describe the mBC pathological characterization; describe frequency of diagnostic tests to define breast cancer molecular subtypes; describe the subsequent line of treatment and corresponding PFS; describe overall survival (OS); evaluate PFS and OS according to visceral vs. non-visceral metastatic disease, primary endocrine resistance vs. acquired endocrine resistance, de novo versus recurrent disease, public vs. private health system and pre vs postmenopausal status. Statistical Methods: No a priori sample size calculation was performed. The expected sample size of 150 patients in each group allows description of the proportion of patients using CDK 4/6 inhibitors with two-sided 90% confidence interval ranging from 53.4% to 66.6% when the expected proportion is 60% in the private health system. Present Accrual and Target Accrual: A total of 12 sites of 14 planned were activated. The first patient was enrolled on February 8, 2022. As of June 24, 2022, a total of 122 patients were enrolled, 86 from public and 36 from private health system. The target accrual of 300 patients is expected to be completed by November 2022. Results are expected to be presented by April 2023. Funding: Novartis. Acknowledgements: SAS. Citation Format: Gustavo Werutsky, Tomás Reinert, Daniela D. Rosa, Romualdo Barroso-Sousa, Heloísa Resende, Poliana A. Signorini, Juliana G. Martins Fagundes, Jose Marcio B. Figueiredo, Eduardo Cronemberger, Aline C. Vieira, Jorge Henrique Santos Leal, Luiza Nardin Weis, Ludmila Thommen, Rafaela G. Jesus, Gustavo Gössling, José Bines. Real-World Data on First-line Treatment of HR-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE Study/LACOG 0221) [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 OT3-07-01.

2636 Background: With the advancements of immunotherapy procedures and, more specifically, immunological checkpoint inhibitors (ICIs), the scenario of cancer treatment, whether in its early or advanced stages, have changed. With the expansion of ICIs usage, cardiovascular toxicities have been reported, but more robust data are needed to guide the follow-up of patients and toxicity prevention. Methods: This research is a single-centered, prospective observational cohort study that evaluated patients treated with ICIs regardless of indication, with or without chemotherapy combination. Patients underwent echocardiography evaluation with global longitudinal strain (GLS) and myocardial work, electrocardiogram, and collection of biomarkers before the start of treatment, in the second month after treatment started, and every 3 months, subsequently. Evaluations stopped once treatment completed one year, or the medication was discontinued either due to toxicity or disease progression. Cardiotoxicity (CT) was defined by ≥ 10% reduction in left ventricular ejection fraction (LVEF) by less than 50%, troponin elevation by ≥ 0,30 ng/ml, or reduction in relative GLS by ≥ 15%. Frequencies were compared using Fisher's comparative test, as appropriate, and Mann-Whitney test for numerical variables. Statistical significance will be considered as p < 0.05 for two-tailed tests. Results: Outof the 98 patients scheduled for treatment, 39 patients underwent at least 2 evaluations and had their exams analyzed. There was a 26% incidence of overall CT, with half of these patients by LVEF reduction criteria and, considering only patients with lung cancer, there was an incidence of 35% with CT. Dividing the total sample into CT and non-CT groups, a higher number of men, smokers and patients with lung cancer was observed, as well as a lower LVEF baseline (67% vs 62.50, p = 0.014) in the CT group. Concomitant chemotherapy or higher baseline coronary calcium scores did not appear to increase the risk of CT among patients, but the use of beta-blockers was restricted to patients who did not develop an event. There was a reduction in myocardial work parameters in the 2nd month assessment: global index (GWI) 1833 vs 2334, p = 0.006, constructive work (GCW) 2299 vs 2683, p = 0.040, and work efficiency (GWE) 83 vs 95, p = 0.025 and tendency towards increased myocardial work loss (GWW) 286 vs 116, p = 0.064, in the comparison between groups. Those who met CT criteria had a longer overall survival, as did those who developed other immune-mediated adverse events and metformin users. Conclusions: This was the first study that carried out cardiotoxicity surveillance in patients undergoing immunotherapy, with a surprising finding of events in a small but high-risk sample. The development of immune-mediated toxicities seems to be related with therapeutic response. Also, the use of metformin seems to contribute to this response, as already demonstrated in preclinical studies.