Abstract P1-17-01: Development of brain metastases in breast cancer patients treated in the neoadjuvant trials Geparquinto and Geparsixto
Authors: Witzel ID , Laakmann E , Fasching PA , Rezai M , Schem C , Solbach C , Tesch H , Klare P , Schneeweiss A , Zahm D , Blohmer J , Ingold-Heppner B , Huober J , Hanusch C , Jackisch C , Reinisch M , Untch M , von Minckwitz G , Müller V , Loibl S 
Published: February 2018

Abstract
Background: The incidence of brain metastases (BM) in breast cancer patients is rising and has become a major clinical challenge. So far, the incidence of BM after modern neoadjuvant treatment is not clear.
Materials and Methods: In Geparquinto, patients with untreated HER2-positive breast cancer (n=615) received either lapatinib or trastuzumab, patients with HER2 negative breast cancer (n=1925) received bevacizumab in addition to an anthracycline and taxane-containing regimen and those not responding paclitaxel and everolimus (n=32). In Geparsixto, patients with HER2-positive tumors (n=273) received trastuzumab and lapatinib and patients with triple-negative tumors (n=315) received bevacizumab in addition to chemotherapy. We analyzed clinical factors associated with the occurrence of BM as first site of metastatic relapse after neoadjuvant treatment in both trials (n=3160).
Results: After a median follow-up of 61 months, 108 (3%) of a total of 3160 patients developed BM as first site of recurrence and 411 (13%) patients had distant metastases outside the brain. Brain metastases as first site of recurrence occurred later than other metastases (3--year-relapse free-rate 96.7% for patients who developed BM and 89.5% for patients who developed metastases outside the brain). Regarding subtypes of the primary tumor, 1% of luminal A (11/954), 2% of luminal B (7/381), 4% of HER2 positive (34/809) and 6% of triple-negative patients (56/1008) developed BM as first site of recurrence. In multivariate analysis, risk factors for the development of BM were larger tumor size (cT3-4; HR 1.9, 95%-CI 1.3-2.8, p=0.0022), node positive disease (HR 2.8, 95% CI 1.8-4.4, p&lt;0.0001), no pCR after neoadjuvant chemotherapy (HR 2.7, 95% CI 1.6-4.7, p=0.0003) and HER2 positive (HR 3.8, 95% CI 1.9-7.8, p=0.0002) or triple-negative subtype (HR 8.1, 95% CI 4.2 – 15.8, p&lt; 0.0001). Breast cancer subtype remained the most relevant risk factor for BM. Patients who developed BM were more often HER2 positive or triple-negative tumors compared with patients who developed metastases outside the brain (HER2 positive subtype 32 vs. 19%, triple-negative subtype 52 vs. 40%, p&lt; 0.001).
Conclusion: Especially patients with HER2-positive and triple negative tumors are at risk of developing BM despite active systemic treatment. A better understanding of the underlying mechanisms is required in order to develop potential preventive strategies.
Citation Format: Witzel ID, Laakmann E, Fasching PA, Rezai M, Schem C, Solbach C, Tesch H, Klare P, Schneeweiss A, Zahm D, Blohmer J, Ingold-Heppner B, Huober J, Hanusch C, Jackisch C, Reinisch M, Untch M, von Minckwitz G, Müller V, Loibl S. Development of brain metastases in breast cancer patients treated in the neoadjuvant trials Geparquinto and Geparsixto [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-17-01.