HER2 POSITIVITY IS ONE OF THE GREATEST RISK FACTORS FOR BRAIN METASTASES IN PATIENTS WITH BREAST CANCER1-6
1 in 2 patients
with HER2+ metastatic breast cancer will develop brain metastases over the course of their disease4,6
- Retrospective data show that patients with tumors overexpressing HER2 develop brain metastases at a higher rate than most patients with HER2-negative tumors, including those with the TN subtype1,7
- Brain metastases in patients with HER2+ MBC, as identified by IHC or ISH, can occur even in patients who are otherwise responding to treatment or who have stable disease at other sites8,9
Cancer cells infiltrate the brain through an intact blood-brain barrier via the process of extravasation, enabling the development of micrometastases. 10-12
Tight junctions restrict paracellular transport through an intact BBB to select molecules and pharmacological compounds with a weight under 400-600 Da and lipid solubility.10, 12-14
Large molecules greater than ~600 Da may not cross an intact BBB due to their size.13,14
Images are for illustrative purposes only and are not to scale.
BBB = blood-brain barrier; Da = dalton; HER = human epidermal growth factor receptor; IHC = immunohistochemistry; ISH = in situ hybridization; MBC = metastatic breast cancer; TN = triple-negative.
References: 1. Aversa C, Rossi V, Geuna E, et al. Metastatic breast cancer subtypes and central nervous system metastases. Breast. 2014;23(5):623-628. 2. Bailleux C, Eberst L, Bachelot T. Treatment strategies for breast cancer brain metastases. Br J Cancer. 2021;124(1):142-155. 3. Koniali L, Hadjisavvas A, Constantinidou A, et al. Risk factors for breast cancer brain metastases: a systematic review. Oncotarget. 2020;11(6):650-669. 4. Olson EM, Najita JS, Sohl J, et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast. 2013;22(4):525-531. 5. Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97(12):2972-2977. 6. Altaha R, Crowell E, Hobbs G, Higa G, Abraham J. Increased risk of brain metastases in patients with HER-2/neu-positive breast carcinoma. Cancer. 2005;103(3):442-443. 7. Wu Q, Li J, Zhu S, et al. Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study. Oncotarget. 2017;8(17):27990-27996. 8. Palmieri D, Bronder JL, Herring JM, et al. Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res. 2007;67(9):4190-4198. 9. Burstein HJ, Lieberman G, Slamon DJ, Winer EP, Klein P. Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy. Ann Oncol. 2005;16(11):1772-1777. 10. Yonemori K, Tsuta K, Ono M, et al. Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer. Cancer. 2010;116(2):302-308. 11. Brosnan EM, Anders CK. Understanding patterns of brain metastasis in breast cancer and designing rational therapeutic strategies. Ann Transl Med. 2018;6(9):163. 12. Witzel I, Oliveira-Ferrer L, Pantel K, Müller V, Wikman H. Breast cancer brain metastases: biology and new clinical perspectives. Breast Cancer Res. 2016;18(8):1-9. 13. Morad G, Carman CV, Hagedorn EJ, et al. Tumor-derived extracellular vesicles breach the intact blood-brain barrier via transcytosis. ACS Nano. 2019;13(12):13853-13865. 14. Pardridge WM. Drug delivery to the brain. J Cereb Blood Flow Metab. 1997;17(7):713-731.