Estrogen receptor (ER) status and survival outcomes in HER2 positive (+) metastatic breast cancer (mBC).

Abstract

e12503 Background: The oncological management of HER2+ mBC is complicated by the development of resistance to HER2-directed therapies (HER2-DTs). This project analyses real-world clinical data to determine disease response patterns that may guide treatment sequencing decisions. Methods: This collaborative project analysed HER2+ mBC datasets held by the Sussex Cancer Centre and Guy’s Cancer Centre, UK. The datasets were generated by reviewing clinical notes, radiology and e-prescribing records to collect clinical data on patients diagnosed with HER2+ mBC between 01/01/2013 – 30/09/2018. Results: 138 patients with a median age of 59 years (30 - 89 years) were diagnosed with HER2+ mBC during this time period: 88 were ER+ (63.7%) and 50 were ER- (36.3%); the median OS is 41.1 mos. (range 0.7 - 62 mos.). Patients with HER2+ mBC were more likely to present with visceral metastases (68.1%, n = 94). A poorer median OS was identified in patients with ER+ HER2+ mBC (35.5 mos.) vs ER- HER2+ mBC (MNR). A benefit to median OS was observed with first line treatment using Docetaxel/Trastuzumab/Pertuzumab (THP) compared to other HER2-DTs ((54.5 mos. (n = 76) vs 26.7 mos. (n = 40)) 65.2% (n = 90) were previously treated for early breast cancer (EBC), evenly distributed across the 2 groups ER+ (64.7%, n = 57) vs ER- (66%, n = 33). 53.7% (n = 50) received trastuzumab with neo-adjuvant/adjuvant therapy (NACT/ACT). Patients previously treated for EBC demonstrated a poorer median OS (34 mos.) when compared to patients with de-novo mBC (MNR). When treated for EBC, ER+ disease was less likely to have a pathological complete response (pCR) with NACT (ER+ 22.2% (n = 4/18) vs ER- 50% (n = 5/10)). PFS data in response to an array of prescribed systemic therapies will be presented. Conclusions: Though, HER2 signalling is considered the dominant signalling pathway in HER2+ breast cancer, pre-clinical research indicates that the ER pathway represents an important escape mechanism influencing the development of resistance. Lack of efficacy (pCR) to NACT in ER+HER2+ EBC may translate to poorer outcomes (OS) when these patients develop MBC. Earlier targeting of the ER pathway in conjunction with HER2-DTs may contribute to improving patient outcomes.