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For researchers

Scientific summary and goal

Breast cancer is the second leading cause of metastases to the central nervous system (CNS) and up to a third of patients with breast cancer are diagnosed with CNS disease.1-3

Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers and has an incidence as high as 50% of brain metastases once patients develop advanced disease.4 TNBC is associated with higher risk of relapse and poor 5-year overall survival.5

TNBC has fewer treatment options than other types of invasive breast cancer. This is because the cancer cells do not have the oestrogen or progesterone receptors or enough of the HER2 protein to make hormonotherapy or targeted HER2 drugs work. Since hormonotherapy and anti-HER2 drugs are not options for women with triple-negative breast cancer, chemotherapy is often used. However, the use of conventional chemotherapy is insufficient in the treatment of tumors or metastases in the brain due to the presence of blood-brain barrier (BBB)/ blood-tumor barrier (BTB), which prevents a sufficient concentration of chemotherapeutics from reaching lesions.6

BREAST-BRAIN-N-BBB project will deliver drug lead(s) and an animal model fitted to serve as tool for TNBC-BM drug development studies. This animal model will be made public for the scientific community. This drug lead will consist of a protein conjugate having triple function: (i) a cancer cell-killing domain that will be released specifically at the tumor site, (ii) an antibody fragment targeting a specific subpopulation of TNBC with therapeutic activity, and (iii) a BBB peptide shuttle of proven efficacy for brain-targeting.

  1. Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22(14):2865-2872.
  2. Tsukada Y, Fouad A, Pickren JW, Lane WW. Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer. 1983;52(12):2349-2354.
  3. Lin NU, Bellon JR, Winer EP. CNS metastases in breast cancer. J Clin Oncol. 2004;22(17):3608-3617.
  4. Zimmer AS. “Triple-Negative Breast Cancer Central Nervous System Metastases from the Laboratory to the Clinic”. Cancer J. 2021;27(1):76-82.
  5. Zhang JF, Liu J, Wang Y, Zhang B. Novel therapeutic strategies for patients with triple-negative breast cancer. Onco Targets Ther. 2016; 9:6519-6528.
  6. Adkins CE, Nounou MI, Mittapalli RK, Terrell-Hall TB, Mohammad AS, Jagannathan R, Lockman PR. A novel preclinical method to quantitatively evaluate early-stage metastatic events at the murine blood-brain barrier. Cancer prevention research (Philadelphia Pa) 2015;8(1):68–76.

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