HER2 targeted therapy and outcome in HER2-equivocal cases after 2018 ASCO/CAP HER2 guideline modification.

Abstract

e14729 Background: The best targeted therapeutic approach for HER2-equivocal cases remains unclear. New ASCO/CAP HER2 guidelines are intended to decrease this ambiguity by combining immunohistochemistry and in situ hybridization to resolve equivocal cases as positive or negative. However, the benefit of anti-HER2 therapy in HER2-equivocal cases is unknown. Methods: We retrospectively reviewed patients who visited MD Anderson from April 2017 to March 2018 with equivocal HER2 results based on the 2013 ASCO/CAP guidelines. The population was divided into 2 cohorts according to biopsy origin (primary cohort: biopsy from breast or axilla; recurrent/metastatic cohort: biopsy from recurrent or metastatic site). HER2 status was redefined using the 2018 ASCO/CAP guidelines. OS and PFS were calculated (Kaplan-Meier method) based on redefined HER2 status and use of HER2 targeted therapy. Results: A total of 139 equivocal results were found. Primary cohort had 90 patients (33 received neoadjuvant and 57 adjuvant therapy). HER2 IHC results were 0 (6.6%), 1+ (37.7%), 2+ (50%), 3+ (1.1%), and no IHC (4.4%). 94% of HER2-equivocal results became HER2 negative. Only 5 patients received anti-HER2 therapy, all of them in the HER2-negative group. After median follow-up of 1.91 yrs, 3 deaths and 8 progressions had occurred. There was no statistically significant association between anti-HER2 therapy and OS (p = 0.67) or PFS (p = 0.49). The recurrence/metastatic cohort had 49 cases with equivocal results. HER2 IHC results were 0 (6.1%), 1+ (22.4%), 2+ (26.5%), and no IHC (44.9%). 55% of HER2-equivocal results became HER2 negative, and only 1 patient received anti-HER2 therapy. After median follow-up of 2.96 yrs, 15 deaths and 35 progressions had occurred. There was no statistically significant association between anti-HER2 therapy and OS (p = 0.61) or PFS (p = 0.78). Conclusions: Most HER2-equivocal results were redefined as HER2 negative using the new ASCO/CAP guidelines. Association between anti-HER2 therapy and OS or PFS according to the new HER2 status was not observed. Although this is a small sample with short follow-up, patients with HER2-equivocal breast cancers seem to have clinical behavior similar to HER2-negative breast cancer.