Clinical Decision-Making After Receptor Conversion Following Neoadjuvant Therapy in Breast Cancer: A Three-Strategy Framework

Background: Receptor conversion following neoadjuvant therapy may alter eligibility for adjuvant systemic therapy in breast cancer. However, current guidelines provide limited recommendations for biomarker-guided treatment adaptation after receptor change. We aimed to characterize clinical decision-making after receptor conversion and identify a framework describing treatment adaptation across clinically relevant receptor conversion scenarios. Methods: A nationwide cross-sectional survey was conducted between August and September 2025 among Polish medical oncologists involved in breast cancer care. The questionnaire assessed receptor reassessment practices and treatment recommendations across five receptor conversion scenarios. Treatment decisions were classified into three predefined strategies—baseline-driven, residual disease-driven, and combined—according to whether they relied on pretreatment biomarkers, residual disease biomarkers, or both. Results: A total of 104 medical oncologists completed the survey. Routine receptor reassessment in residual disease was reported by 52.9% of respondents, while 73.1% incorporated residual disease biomarkers into treatment planning either routinely or selectively. Overall, baseline-driven strategies accounted for only 26.3% of treatment decisions, compared with 40.2% for combined strategies and 33.5% for residual disease-driven strategies. Combined strategies predominated following hormone receptor conversion (52.9% for luminal HER2-negative to TNBC and 55.8% for TNBC to luminal HER2-negative). Baseline-driven approaches were most frequently selected following HER2 loss (42.3%), whereas HER2 gain favored residual disease-driven strategies in TNBC-to-HER2-positive conversion (46.2%) and combined strategies in luminal HER2-negative-to-HER2-positive conversion (48.1%). Conclusions: A three-strategy framework of clinical decision-making emerged after receptor conversion, with most treatment decisions incorporating residual disease biology despite limited guideline direction. This framework highlights an important evidence gap and provides a practical foundation for future studies evaluating treatment adaptation after receptor conversion.