Background: The treatment landscape in HR+/HER2− metastatic breast cancer (mBC) is continuously evolving, with evidence on new agents and combinations published almost every year. Despite updated therapeutic guidelines, second-line (2L) selection may be challenging due to clinical factors, biomarker status, and available agents. Methods: A two-round Delphi consensus was organized in July 2024, gathering input from 10 experts in research, diagnosis, and treatment of HR+/HER2− mBC on optimal 2L and beyond choice, considering the available biomarkers and results from published clinical trials. Consensus was defined as 70% agreement or disagreement. Results: The experts considered initially a list of 39 statements, structured into the following four sections: biomarker testing; selection of 2L treatment at progression of disease on first line endocrine therapy (ET) + CDK4/6i at ≥6 months after initiation of ET for mBC; selection of 2L treatment at disease progression on ET + CDK4/6i, at <6 months after initiation of ET for mBC, whilst on ET; and selection of post-2L treatment options. After a discussion, the experts decided to remove four statements, refine ten, and include three new ones. The final list consisted of 38 statements, and consensus was achieved in 37. Conclusions: The panel recommends next-generation sequencing as the method of choice for genomic characterization at disease progression on first line. The optimal agent or treatment class is indicated depending on the presence of specific mutations; however, the panel admits that the strategy is different in clinical practice, where novel therapies might not be available or reimbursed.

Background and Objectives: Although clinically useful, homologous recombination deficiency (HRD) testing has recently been more broadly adopted in ovarian cancer (OC) management. The VALIDATE study evaluated HRD status and treatment patterns in patients with newly diagnosed advanced OC in Bulgaria to better understand HRD prevalence and disease management. Materials and Methods: This real-world, observational, multi-centre, medical chart review study included 100 adult patients with HRD testing results available at study entry. Data collected at least 30 days after HRD results and 6 months later were descriptively analysed in the full cohort and subgroups (HRD, BRCA mutation, and genomic instability score [GIS]). Results: Mean age at diagnosis: 61.3 years; stage III: 51.0%, prevalence of HRD+ 58.0% (95% confidence intervals [CI] 47.7–67.8%) and HRD− 42.0% (95% CI 32.2–52.3%). Among the 58 HRD+ patients, 20 (34.5%) were BRCA+, whereas 38 (65.5%) were BRCA−, and 52 (89.7%) were GIS+, and 6 (10.3%) GIS−. Overall, platinum–taxane chemotherapy plus antiangiogenics was the most common front-line (FL) treatment (77.0%), regardless of subgroups (range: 66.7–85.0%). Six months later, 81 patients were alive, and 73 (90%) started maintenance therapy (MT). Antiangiogenic monotherapy (32.0%) and antiangiogenic plus PARP inhibitor (34.0%) were the most common MTs. The latter was also common across subgroups (range: 33.3–60.5%), except for HRD− (61.9% received antiangiogenic monotherapy). Conclusions: In this dataset, more than half of advanced OC patients had HRD+ status. Our study provides relevant insights into recent clinical practice patterns in advanced OC in Bulgaria that could serve as an anchor for future, more robust research in this field.