Less endocrine therapy in HR+/HER2- breast cancer: a nationwide trend despite unchanged guidelines

Background: Adjuvant systemic therapy has improved breast cancer outcomes over the past decades. Following the distinction of molecular subtypes and the introduction of gene expression profiling and prognostic tools, chemotherapy is less frequently recommended for hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer. However, recommendations for endocrine therapy (ET) remained unchanged. This study examines ET trends among HR+/HER2- patients in the Netherlands and factors influencing these trends. Methods: All HR+/HER2- patients diagnosed between 2012 and 2022 who underwent surgery were selected from the Netherlands Cancer Registry. Patients were categorized by ET guideline indications: no indication; indication based on pathological, postoperative TNM-stage/grade; or indication based on clinical TNM-stage/grading on biopsy warranting neoadjuvant chemotherapy (NAC). The ET benefit was estimated for all patients using the PREDICT 2.0 tool. Logistic regression was used to identify factors associated with ET initiation. Results: The study included 127,610 HR+/HER2- patients. The proportion starting ET according to guideline recommendations decreased from 91.2 % (2012) to 79.3 % (2022), with those who did not initiate ET having a lower PREDICT-estimated benefit (1.0 %) compared to those who did (1.5 %). Reduced ET initiation was associated with age 30–39, age >80, and treatment in academic hospitals. In 2022, ET initiation varied by up to 19 percentage points across regions, while the PREDICT-estimated benefit showed no clinically relevant difference (ranging from 1.3 % to 1.5 %). Conclusion: Despite unchanged guideline recommendations, fewer patients started ET over time. This trend, and regional variation, suggests that a more reticent approach by physicians to initiating ET for HR+/HER2- breast cancer may be contributing to it.