Abstract PS14-20: Retrospective analysis of time to progression intracranially in HER2+ breast cancerpatients with brain metastases who receive treatment with radiation
Authors: Nemunaitis Jacklyn Marie , Mehta Krisha , Liu Selina , Brown-Glaberman Ursa , Stopeck Alison 
Published: February 2021

Abstract
Human epidermal growth factor receptor 2 (HER2) positive (+) breast cancer is a disease with distinct clinicopathological features. Survival for women with HER2+ disease has increased with the development of novel systemic therapeutic agents, however the brain is increasingly reported as the first site of relapse. As patients with HER2-positive breast cancer live longer, CNS progression after radiation therapy and / or surgery is an emerging clinical challenge. The average progression free interval intracranially is unknown for women who receive radiation for brain metastases while on modern HER2 targeted therapy. Multiple novel systemic agents are under investigation for the treatment of HER2 positive breast cancer metastatic to the brain. In order to establish a historical control for early phase clinical trials, understanding this time to progression is critical. In our retrospective chart review, we sought to determine the time to progression intracranially for women with HER2+ breast cancer who receive CNS radiation and/or surgery while on modern HER2 targeted systemic therapy. We present preliminary results from our review of 48 patients with HER2+ breast cancer with brain metastases treated at two academic referral centers between 2010-2017. 36 of these patients received some form of local therapy for brain metastases. Mean age at the time of diagnosis with primary breast cancer was 52, with a mean age of 55 at the time of diagnosis of brain metastases. The minority of patients (n=16) were stage IV at the time of their initial diagnosis. Standard of care systemic treatment was given in 43/48 cases. Mean length of time from the diagnosis of the primary breast cancer to the diagnosis of brain metastases was 34.6 months, including 3 patients diagnosed at initial presentation and at the other extreme, 2 patients diagnosed 9 years after their primary diagnosis of cancer. Of the patients who received treatment for brain metastases and for whom data was available (n=33), mean time from first treatment for brain metastases to first brain recurrence was 8.24 months (range: 1 to 24 months). 7 patients (21%) recurred within 3 months. In 9 patients mortality data was available. Mean time from treatment to death was 20 months (range 1 - 58 months). For patients who underwent surgery alone as primary treatment, mean time until first recurrence was 7.1 months (n=14), compared with a mean of 7.8 months for patients who received WBRT (n=26). Patients who received both surgery and radiation as a primary treatment had a mean time from first treatment to recurrence of 11.5 months (n=4). Only 34% of patients changed systemic treatment after the diagnosis of brain metastases. 5 patients had brain metastases as their only site of measurable disease. Only 1 of these patients had a change in systemic treatment after the diagnosis of brain metastases. These results suggest that the time from initial local treatment for brain metastases to recurrence is devastatingly short. Future clinical trials in metastatic HER2+ breast cancer should consider the impact novel therapeutics have on brain metastases in addition to overall and progression free survival. These data provide a historical reference for evaluating the impact of novel therapies on HER2-postive brain metastases.
Citation Format: Jacklyn Marie Nemunaitis, Krisha Mehta, Selina Liu, Ursa Brown-Glaberman, Alison Stopeck. Retrospective analysis of time to progression intracranially in HER2+ breast cancerpatients with brain metastases who receive treatment with radiation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-20.