Clinicopathological characteristics of exceptional responders who achieve durable remissions beyond five years (DR5) in HER2+(H+) metastatic breast cancer (MBC).

person Darko Skrobo St Vincent's University Hospital, Dublin, Ireland info_outline Darko Skrobo, Naomi Walsh, Jose Berenguer, Janice Maria Walshe, Michaela Jane Higgins, David William Fennelly, Jo Ballot, Cecily Quinn, Giuseppe Gullo, John Crown

Authors person Darko Skrobo St Vincent's University Hospital, Dublin, Ireland info_outline Darko Skrobo, Naomi Walsh, Jose Berenguer, Janice Maria Walshe, Michaela Jane Higgins, David William Fennelly, Jo Ballot, Cecily Quinn, Giuseppe Gullo, John Crown Organizations St Vincent's University Hospital, Dublin, Ireland, National Institute for Cellular Biotechnology, Dublin City University (DCU), Dublin, Ireland, NSABP/NRG Oncology, and Cancer Trials Ireland, St Vincent's University Hospital, Dublin, Ireland, Mater Misericordiae University Hospital, Dublin, Ireland, St. Vincent's University Hospital, Dublin, Ireland, Department of Pathology and Laboratory Medicine, St. Vincent's University Hospital, Dublin, Ireland, NSABP/NRG Oncology, and The Irish Cooperative Oncology Research Group, Dublin, Ireland Abstract Disclosures Research Funding Other Cancer Clinical Research Trust Background: The introduction of anti-H2 targeted therapies has resulted in substantially improved outcomes for patients (pts) with H+MBC, yet despite survival prolongation, most patients so-treated will still ultimately die from MBC. Some patients do however, achieved prolonged remissions. In this report we outline the long-term outcomes of patients with H+MBC who were treated in our institution, with at least five-year follow-up from the diagnosis of MBC. Methods: As part of our larger single-institution “Thousand Patient HER-2 Database”, we conducted a retrospective review of all patients in whom a diagnosis of H+MBC was made prior to December 2015 (range 2000-2015 years). The DR5 category included only those who had never experienced relapse or progression following initial anti-H2 therapy for MBC, and who were alive at 5 years. Patients were designated as (1) DR5, defined as never relapse with an overall survival (OS) > 5 years; (2) nonDR, which included those who had no or shorter remission, but also included nine pts who did achieve a 5 year CR, but who subsequently relapsed. OS was calculated from the date of diagnosis of MBC. The frequency distribution was assessed by Fisher’s Exact Test or Chi-Square Test, as appropriate. OS and PFS were calculated according to Kaplan Meier method, and evaluated by Log-rank test. Univariate and multivariate Cox proportional hazards regression analysis was used to evaluate the effect of clinicopathological features on OS and PFS. Results: A total of 245 patients diagnosed with advanced H+MBC were identified. The median survival was 38 months, (range 0.3 – 248 months). Among these, 85 patients (35%) experienced an OS > 5 years, with 34 designated as DR5. The median OS for DR5 was 117 months, whereas nonDR (n = 211) had median OS of 33 months. The median age was similar between groups (DR5 53 yrs vs nonDR 56 yrs). A higher incidence of visceral disease was present in nonDR compared to DR5 (69% vs 44%). Of all patients diagnosed with de novo H+MBC, 23% achieved DR5. Presence of visceral disease, number of metastases and site of metastases were statistically significant negative predictors of achieving DR5 (P < 0.05). Presence of ER positive disease was not associated with OS. Conclusions: A meaningful subset of patients (14%) with advanced H+MBC achieve prolonged remission beyond five years with H2 targeted therapy. Nearly one quarter of those with de novo H+MBC achieve DR5. As de novo H+MBC now constitutes a higher proportion of all H+MBC than it did in the pre-trastuzumab era, an increasing proportion of H+MBC may now be achieving DR5. Prospective identification of variables to predict DR5 could assist in the stratification of patients for whom additional therapy is needed.