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

person Karen DeSouza Brighton and Sussex Medical School, Brighton, United Kingdom info_outline Karen DeSouza, Rosa-Rita Zammit, Anna Haire, Rajesh Sinha, Richard Simcock, Charlotte Hannah Moss, Anca Mera, Janine Mansi, Eleni Karapanagiotou, Elinor Sawyer, Gargi Surendra Patel

Authors person Karen DeSouza Brighton and Sussex Medical School, Brighton, United Kingdom info_outline Karen DeSouza, Rosa-Rita Zammit, Anna Haire, Rajesh Sinha, Richard Simcock, Charlotte Hannah Moss, Anca Mera, Janine Mansi, Eleni Karapanagiotou, Elinor Sawyer, Gargi Surendra Patel Organizations Brighton and Sussex Medical School, Brighton, United Kingdom, Sussex Cancer Centre, Brighton, United Kingdom, Guy's Cancer Centre, London, United Kingdom, King's College, London, London, United Kingdom, King's College London, London, United Kingdom Abstract Disclosures Research Funding Pharmaceutical/Biotech Company 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.