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Is Molecular Tailored-Therapy Changing the Paradigm for CNS Metastases in Breast Cancer?

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Abstract

Breast cancer (BC) is the second most common tumour spreading to the central nervous system (CNS). The prognosis of patients with CNS metastases depends on several parameters including the molecular assessment of the disease. Although loco-regional treatment remains the best approach, systemic therapies are acquiring a role leading to remarkable long-lasting responses. The efficacy of these compounds diverges between tumours with different molecular assessments. Promising agents under investigation are drugs targeting the HER2 pathways such as tucatinib, neratinib, pyrotinib, trastuzumab deruxtecan. In addition, there are several promising agents under investigation for patients with triple-negative brain metastases (third-generation taxane, etirinotecan, sacituzumab, immune-checkpoint inhibitors) and hormone receptor-positive brain metastases (CDK 4/5, phosphoinositide-3-kinase-mammalian target of rapamycin [PI3K/mTOR] inhibitors). Also, the systemic treatment of leptomeningeal metastases, which represents a very negative prognostic site of metastases, is likely to change as several compounds are under investigation, some with interesting preliminary results. Here we performed a comprehensive review focusing on the current management of CNS metastases according to molecular subtypes, site of metastases (leptomeningeal vs brain), and systemic treatments under investigation.

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  1. Department of Oncology, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy

    Vincenzo Di Nunno, Enrico Franceschi, Alicia Tosoni, Antonella Mura, Santino Minichillo, Monica Di Battista, Lidia Gatto, Ilaria Maggio, Stefania Bartolini & Alba Ariela Brandes

  2. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

    Raffaele Lodi

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  1. Vincenzo Di Nunno
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Conceptualisation: VDN and EF; data curation: AT, LG, MDB, IM; investigation: all authors, methodology: all authors; supervision: RL, SB, AAB; validation: RL, AAB; writing original draft: VDN, AM, SM; Writing review and editing: VDN, AT, LG, IM.

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Di Nunno, V., Franceschi, E., Tosoni, A. et al. Is Molecular Tailored-Therapy Changing the Paradigm for CNS Metastases in Breast Cancer?. Clin Drug Investig 41, 757–773 (2021). https://doi.org/10.1007/s40261-021-01070-1

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