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Actual, Personalized Approaches to Preserve Cognitive Functions in Brain Metastases Breast Cancer Patients.

ABSTRACT: Breast cancer (BC) is the most often diagnosed cancer among women worldwide and second most common cause of brain metastases (BMs) among solid malignancies being responsible for 10-16% of all BMs in oncological patients. Moreover, BMs are associated with worse prognosis than systemic metastases. The quality of life (QoL) among brain metastases breast cancer (BMBC) patients is significantly influenced by cognitive functions. Cancer-related cognitive deficits and the underlying neural deficits in BMBC patients can be caused via BMs per se, chemotherapy administration, brain irradiation, postmenopausal status, or comorbidities. Brain RT often leads to cognitive function impairment by damage of neural progenitor cells of the hippocampus and hence decreased QoL. Sparing the hippocampal region of the brain during RT provides protective covering of the centrally located hippocampi according to the patient's clinical requirements. This article discusses the personalized strategies for treatment options to protect cognitive functions in BMBC patients, with special emphasis on the innovative techniques of radiation therapy.

SUBMITTER: Konopka-Filippow M

PROVIDER: S-EPMC9265102 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Actual, Personalized Approaches to Preserve Cognitive Functions in Brain Metastases Breast Cancer Patients.

Konopka-Filippow Monika M Hempel Dominika D Sierko Ewa E

Cancers 20220625 13

Breast cancer (BC) is the most often diagnosed cancer among women worldwide and second most common cause of brain metastases (BMs) among solid malignancies being responsible for 10-16% of all BMs in oncological patients. Moreover, BMs are associated with worse prognosis than systemic metastases. The quality of life (QoL) among brain metastases breast cancer (BMBC) patients is significantly influenced by cognitive functions. Cancer-related cognitive deficits and the underlying neural deficits in ...[more]

PMID: 35804894

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Project description:Brain metastases are common to the natural history of many advanced malignancies. Historically, whole brain radiation therapy (WBRT) has played a key role in the management of brain metastases, especially for patients with multiple lesions. However, prospective trials have demonstrated consistent neurocognitive toxicities after WBRT, and various pharmacologic and anatomic strategies designed to mitigate these toxicities have been studied in recent years. Memantine, an NMDA receptor antagonist, taken during and after WBRT improved cognitive preservation in a randomized trial over placebo. Deliberate reductions in radiation dose to the hippocampus, via hippocampal-avoidance (HA)-WBRT, resulted in improved cognition over historic controls in a phase II trial, and follow-up randomized trials are now ongoing to evaluate cognitive outcomes with HA vs. conventional brain radiation techniques. Nevertheless, some of the most promising strategies currently available to reduce the cognitive effects of brain radiation may be found in efforts to avoid or delay WBRT administration altogether. Stereotactic radiosurgery (SRS), involving focused, high-dose radiation to central nervous system (CNS) lesions with maximal sparing of normal brain parenchyma, has become the standard for limited brain metastases (classically 1-3 or 4 lesions) in the wake of multiple randomized trials demonstrating equivalent survival and improved cognition with SRS alone compared to SRS plus WBRT. Today, there is growing evidence to support SRS alone for multiple (?4) brain metastases, with comparable survival to SRS alone in patients with fewer lesions. In patients with small-cell lung cancer, the routine use of prophylactic cranial irradiation (PCI) for extensive-stage disease has been also been challenged following the results of a randomized trial supporting an alternative strategy of MRI brain surveillance and early salvage radiation for the development of brain metastases. Moreover, new systemic agents are demonstrating increasing CNS penetration and activity, with the potential to offer greater control of widespread and microscopic brain disease that was previously only achievable with WBRT. In this review, we endeavor to put these clinical data on cognition and brain metastases into historical context and to survey the evolving landscape of strategies to improve future outcomes.

Project description:BackgroundUp to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital.Patients and methodsA total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype.ResultsPatients with HER2-positive breast cancer and BMs were-when compared with HER2-negative patients-slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus <60 years: hazard ratio (HR) 1.63, P < 0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P < 0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P < 0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P < 0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups.ConclusionsWe identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.

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Actual, Personalized Approaches to Preserve Cognitive Functions in Brain Metastases Breast Cancer Patients.

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Actual, Personalized Approaches to Preserve Cognitive Functions in Brain Metastases Breast Cancer Patients.

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