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

1046 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.