Evaluation of human epidermal growth factor receptor 2 overexpression (HER2+) after administration of neoadjuvant treatment (NAT) and prognostic impact in breast cancer (BC)

Abstract

Background: HER2+occurs in 15-20% of BC and is associated with worse prognosis. While previous studies reported that NAT-associated changes in HER2 status adversely affect patients (pts) prognosis (Guarneri et al), others did not (Yoshida et al). To assess the efficacy of NAT in pts with HER2+ BC and its influence on HER2 status and associated prognostic impact. HER2 status was determined by immunohistochemically (IHC) or Silver in situ hybridization (SISH). Methods: Retrospective chart review and pathologic evaluation of all consecutive pts with HER2+ BC (defined as IHC 3+ or IHC 2+ confirmed by SISH) submitted to NAT between Jan2010 and Oct2015 in 3 Portuguese Hospitals. All diagnostic tumor biopsies and surgical specimens were assessed for IHC. Results: 108 female pts were included (median age 52yo, range 30-82; TNM stage was III in 68, II in 40. Hormone receptor (HR) were positive (ER and/or PR) in 68. HER2 status at diagnosis was IHC 3+ in 100 pts and IHC 2+ SISH amplified in 8. NAT included chemotherapy (CT) in all pts (anthracyclines (AC)/ taxanes (Tax) 102, AC/ non-Tax 3, non-AC regimen 3), trastuzumab (T) in 87 and T and pertuzumab (P) in 3. Pathological complete response (pCR) (ypT0/isN0) was achieved in 48 pts (44.4%): 28 of 70HR+ and 20 of 38HR neg (p=0.2), 27 of 40 with stage II and 21 of 68 with stage III (p<0.001). pCR rate was 46% after CT+T/P and 39% with CT alone (p=0.6). With a median follow-up of 55 months, there were 5 disease free survival (DFS) events (4 relapses and 1 non-BC death) among pCR pts and 19 among non-pCR (16 relapses and 3 non-BC deaths) (p=0.02, log rank test). Of the 60 pts with residual invasive tumor at surgery, 52 remained HER2+ and 8 (13.3%) lost Her2+. 5y-DFS and 5-OS is 70% and 84%, respectively, for pts whose tumors remained HER2+(14 DFS events; 8 deaths), and 21% and 50% for pts whose residual tumors became HER2 negative (5 DFS events; 4 deaths) (p=0.02 and<0,001, log-rank test). Conclusions: We confirmed the negative prognostic impact of NAT-induced HER2 loss on residual tumor leading to worse DFS. Despite the retrospective design and small sample size, these results suggest the importance of retesting HER2 after NAT, to better refine pts prognosis.