Development of risk stratification tool to appropriately triage the patients at risk of recurrence in HR+ HER2- early breast cancer

Introduction: HR+/HER2-negative Early Breast Cancer (EBC) is treated with curative intent, but managing locoregional and distant recurrences remains a significant challenge. The lack of a standard risk-identification approach leads to varied assessments across centers. Developing a robust risk assessment tool that incorporates guideline updates, AJCC classification, and clinical trials in a simplified manner is essential to mitigate recurrence risk (RoR).

Objective: To develop an effective risk assessment tool to manage and mitigate the RoR in patients with HR+ HER2 –ve early breast cancer incorporating multidisciplinary perspectives and evolving evidence/guidelines and trials.

Methodology: Multiple workshops were conducted across India to enhance the understanding and management of risk in EBC among the multidisciplinary teams involved in EBC management.

The steps to arrive at the algorithm are as follows-

1.Understanding Current Practices: To understand the current clinical practice of the participants, a preliminary poll consisting of 10 questions was conducted. Following this, Participants were divided into three to four groups for case- based discussion. During the group activity, they shared their current risk assessment and treatment practices for node positive and node negative cases.

2.Exploring Evolving Evidence: Following the group activity, a deep dive review of current literature on RoR in both node-positive and node-negative cases, as well as emerging evidence on the use of adjuvant therapy in EBC. Following each topic, a post-polling of relevant questions was conducted to determine any changes in the participants' beliefs regarding risk assessment in node-positive and node-negative EBC.

3.Ideation and Development: Based on the post-polling results, each component of the algorithm was populated. For components with less than 70% agreement, further discussion was conducted to reach a common alignment. Basis this a comprehensive, quick-reference, and user-friendly algorithm for risk assessment was developed.

Results: Five workshops were conducted with 135 multidisciplinary experts: 72 medical oncologists (53.3%), 28 onco- surgeons (20.7%), 26 radiation oncologists (19.3%), and 9 onco-pathologists (6.7%). All N2 patients were unequivocally considered at high ROR by all participants. In addition to nodal status, a tumour size > 5 cm was considered at high risk of recurrence by 59% versus 93% participants in pre and post polling survey respectively. 94.5% versus 58.8% (post versus pre) participants agreed that patients with N1 status are unequivocally at high risk of recurrence. It was agreed that grading and Ki-67 are key deciding risk stratification factors in patients with N0 tumour with T<5 cm for selection of adjuvant treatments by 74% participants in the post polling. Ki-67 cut off ≥ 20% was considered as critical to consider your patients at higher risk of progression by 100% post-polling vs 77% pre-polling.

Conclusion: The approach to managing early breast cancer (EBC) is evolving. We implemented a unique methodology using a common questionnaire across different expert group to arrive at a standardized tool for risk assessment in HR+, HER2 -ve EBC patients across India. This tool simplifies the risk stratification approach for EBC patients and can help standardize approach to patient management across healthcare sectors.