Impact of Hormone Receptor Status on Development of Brain Metastases from HER2+ Breast Cancer

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<h3>Purpose/Objective(s)</h3> Patients with HER2+ breast cancer (BC) are at high risk of developing and dying from brain metastases (BM) compared to patients who have HER2- disease. Some studies have suggested hormone receptor (HR) positivity can delay the development of BM possibly due to endocrine therapies controlling extracranial disease. However, the impact of HR positivity on the time to development of BM in HER2+ disease is not well understood. <h3>Materials/Methods</h3> We retrospectively reviewed data on patients with BM from BC from a single academic institution from 2005–2020, during which time trastuzumab was included in the standard of care. Patients with HER2+ BC and BM were stratified into groups based on HR status, i.e., ER+ and/or PR+. Overall survival (OS) data was analyzed using the Kaplan-Meier method with differences compared by the log-rank test. HR status and time to development of BM were compared using a two-tailed Student's t-test. <h3>Results</h3> Of 363 BC patients with BM, 67 patients (18.5%) were identified as HER2+ (median age 48; range 26–80). 63 (94%) of the 67 patients received trastuzumab. 39 (58.2%) of the 67 patients had HR+ disease (ER+ and/or PR+ disease) and 28 (41.8%) had HR- disease. 30 (76.9%) of 39 patients with HR+ disease received endocrine therapy. In HR+ patients, the median time to the diagnosis of BM was 48.4 mos (SD=57.9 mos), while in patients with HR- disease the median time to the diagnosis of BM was shorter at 29.0 mos (SD=49.1 mos) (p<0.02). The median OS after initial diagnosis of BM for patients with HR+ disease was 27.6 mos, and 9.8 mos for patients with HR- disease (p<0.46). Of the 67 patients, 20 (29.9%) patients presented with one BM, 23 (34.3%) with 2–9 BM, 17 (25.4%) patients with ≥10 BM, and 7 (10.4%) with unknown number of BM. The median number of BM in HR+ patients was 2.0 (SD=2.8), and the median number of BM in HR- patients was 1.0 (SD=3.2) (p<0.43). The median diameter of the dominant BM in HR+ patients was 2.5 cm (SD=1.4 cm; range=0.05–5.4 cm), and the median diameter of the dominant BM in HR- patients was 2.1 cm (SD=1.2 cm; range=0.2–4.4 cm) (p<0.14). Brain imaging was obtained for neurological symptoms in 45 (67.2%) patients; 5 (7.5%) were asymptomatic; and 17 (22.4%) had unknown indication for imaging. 30 patients (44.8%) had extracranial metastases at the initial time of HER2+ BC diagnosis, and their median time to the development of BM was 26.4 mos (SD=25.2 mos). In contrast, 34 patients (50.7%) had no extracranial or BM at BC diagnosis and had longer median interval time to BM development at 53.8 mos (SD=67.5 mos) (p<0.002). <h3>Conclusion</h3> The majority of patients with HER2+ BM were symptomatic at time of BM diagnosis. The most salient factors associated with a decreased time interval to development of BM included HR- status and presence of extracranial metastases at the time of initial HER2+ BC diagnosis.