Challenges in identifying HER2-low metastatic breast cancer: Real-world perspectives from a nationwide pathologist survey.

Abstract

e13138 Background: HER2-low/ultralow metastatic breast cancer (mBC) is now clinically actionable with HER2-directed antibody–drug conjugates, but expanding HER2 classification beyond a binary model has increased diagnostic complexity and variability in practice. A prior quality improvement (QI) initiative identified diagnostic and therapeutic gaps among community oncologists, including ambiguous results, inconsistent HER2 testing and reporting, limited multidisciplinary communication, and uncertainty in applying HER2 results to treatment decisions. Building on these findings, we surveyed pathologists nationwide to characterize real-world HER2 testing and reporting practices and identify diagnostic and care coordination barriers between specialties. Methods: From May–June 2025, 100 pathologists completed surveys assessing HER2 testing workflows, interpretation, and classification challenges, including barriers to coordinating with oncologists, with key items tethered to the prior oncology survey. Results: The majority of respondents reported practicing in community-based hospitals and clinics (58%). Sixty-three percent of pathologists identified risk of HER2 misclassification as the greatest challenge in identifying HER2-low/ultralow mBC, compared with 21% of oncologists surveyed in the prior QI initiative, whose top challenge was interpreting ambiguous or borderline results. Similar proportions of pathologists and oncologists reported difficulty interpreting ambiguous or borderline results (53% vs 51%) and limited familiarity with the clinical relevance of lower HER2 expression (28% vs 24%), while inconsistencies in testing and reporting were cited by 55% and 24%, respectively. Pre-analytic and analytic barriers included tumor heterogeneity (52%), suboptimal sample conditions (43%), and inadequate clinical information (39%). Evolving HER2 classification was the most common reporting challenge (76%), and only 47% of pathologists felt comfortable distinguishing HER2 IHC 0 from IHC 1+. Fewer than half of pathologists and oncologists reported that HER2-low status was routinely specified in pathology reports 41% and 37%, respectively. Collaboration with oncologists is hindered by understanding of HER2 testing guidelines (58%), pressure to alter or expedite reporting (28%), and communication through intermediaries (26%). To improve identification, nearly two-thirds of pathologists favored workflows to better differentiate IHC 0 versus 1+, and 58% supported standardizing definitions and documentation. Conclusions: Persistent diagnostic variability and inconsistent reporting limit accurate identification of HER2-low and HER2-ultralow mBC, underscoring the need for standardized workflows, clearer reporting, and improved multidisciplinary coordination between pathologists and oncologists.