Analysis of Rates of Brain Metastases and Association With Breast Cancer Subtypes in Ontario, Canada

Wang, Xin Ye; Rosen, Michael N.; Chehade, Rania; Sahgal, Arjun; Das, Sunit; Saskin, Refik; Zhang, Bo; Soliman, Hany; Chan, Kelvin; Jerzak, Katarzyna J.

doi:10.1001/jamanetworkopen.2022.25424

Cited by 11 publications

(4 citation statements)

References 39 publications

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“…However, almost half (49.4%) had an unknown molecular subtype. 4 In comparison, in our study, 31.1% of patients had an unknown molecular subtype, including 21.1% of the BrM cohort. A metanalysis from Kuksis et al reported that the pooled CI of BrM in metastatic BC patients was approximately 31% in ERBB2+, 32% in HR-negative/ERBB2-, and 15% in the HR+/ERBB2-cohorts.…”

Section: Discussionmentioning

confidence: 45%

The incidence of brain metastases in breast cancer according to molecular subtype and stage: a 10-year single institution analysis

Poletes,

Amanirad,

Santiago

et al. 2024

J Neurooncol

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BackgroundBreast cancer (BC) is the second most common etiology of brain metastases (BrM). We aimed to examine the incidence of BrM among all BC patients presenting to a large tertiary cancer centre over one decade. MethodsWe included all BC patients presenting consecutively between 2009 and 2019 and cross referenced that cohort to a radiotherapy database, identifying patients treated for BrM at any time following their initial presentation. Cumulative incidences (CI) of BrM diagnoses were calculated using death as a competing risk and compared using the Fine-Gray method. Overall survival was estimated using the Kaplan Meier method. ResultsWe identi ed 12,995 unique patients. The CI of BrM in patients who initially presented with Stage 0-4 disease was 2.1%, 3.7%, 9.4%, 10.6%, and 28.7%, respectively at 10 years. For 8,951 patients with available molecular subtype data, 6,470 (72%), 961 (11%), 1,023 (11%), and 497 (6%) had hormonereceptor (HR)-positive/ERBB2-, HR-negative/ERBB2-, HR-positive/ERBB2+, and HR-negative/ERBB2+ disease, respectively; the CI of BrM in each was 7.6%, 25.3%, 24.1%, and 26.6%, at 10 years following BC diagnosis, respectively. Median overall survival (OS) following BC diagnosis and BrM diagnosis was 28 years 95% CI [25, 32] and 10 months 95% CI [9,12], respectively. ConclusionsFrom a large, registry-based study, we observed that patients with ERBB2+ and triple negative BC have the highest incidence of BrM. Clinicians should have a low threshold for brain imaging in patients with a history of BC who experience symptoms suggestive of BrM, especially in ERBB2+ and triple negative BC.

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Section: Discussionmentioning

confidence: 45%

The incidence of brain metastases in breast cancer according to molecular subtype and stage: a 10-year single institution analysis

Poletes,

Amanirad,

Santiago

et al. 2024

J Neurooncol

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“…Although there was no difference in the overall number of systems with metastasis, the reticuloendothelial and digestive systems were significantly more frequently involved in the BRCA2 carriers compared with non‐carriers with prostate cancer. This observation of a predilection for certain organ systems in carriers with specific tumour subtypes, in addition to the hypothesis of the microenvironment supporting a shorter time for metastatic tumour growth in some organs, as described in brain metastases, 29,30 highlights the opportunity to define these underlying mechanisms. Further interrogation of the autopsy samples together with the differences in the ‘soil’ of the sites will help to identify the key processes that drive the observed differential tumour metastases and help in the recognition of potential new pathways for treatments.…”

Section: Discussionmentioning

confidence: 89%

BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non‐carriers: results from a rapid autopsy programme

Thorne

Devereux

et al. 2023

Histopathology

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“…Approximately 45% of patients diagnosed with advanced TNBC develop distant metastasis to CNS and/or visceral organs, with a median OS of 13.3 months [ 23 ]. Another study indicated that the TNBC subtype is significantly correlated with a shorter time between the diagnosis of metastasis and treatment for brain metastasis with radiotherapy, with a median time of 7.5 months [ 24 ]. Consistently, our TNBC cohort had a higher proportion of patients with metastases than the non-TNBC group, with more metastatic sites and brain metastases, demonstrating the metastatic ability of TNBC.…”

Section: Discussionmentioning

confidence: 99%

PRR15 deficiency facilitates malignant progression by mediating PI3K/Akt signaling and predicts clinical prognosis in triple-negative rather than non-triple-negative breast cancer

Guo

Liu

et al. 2023

Cell Death Dis

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Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast neoplasms with a higher risk of recurrence and metastasis than non-TNBC. Nevertheless, the factors responsible for the differences in the malignant behavior between TNBC and non-TNBC are not fully explored. Proline rich 15 (PRR15) is a protein involved in the progression of several tumor types, but its mechanisms are still controversial. Therefore, this study aimed to investigate the biological role and clinical applications of PRR15 on TNBC. PRR15 gene was differentially expressed between TNBC and non-TNBC patients, previously described as an oncogenic factor in breast cancer. However, our results showed a decreased expression of PRR15 that portended a favorable prognosis in TNBC rather than non-TNBC. PRR15 knockdown facilitated the proliferation, migration, and invasive ability of TNBC cells in vitro and in vivo, which was abolished by PRR15 restoration, without remarkable effects on non-TNBC. High-throughput drug sensitivity revealed that PI3K/Akt signaling was involved in the aggressive properties of PRR15 silencing, which was confirmed by the PI3K/Akt signaling activation in the tumors of PRR15Low patients, and PI3K inhibitor reversed the metastatic capacity of TNBC in mice. The reduced PRR15 expression in TNBC patients was positively correlated with more aggressive clinicopathological characteristics, enhanced metastasis, and poor disease-free survival. Collectively, PRR15 down-regulation promotes malignant progression through the PI3K/Akt signaling in TNBC rather than in non-TNBC, affects the response of TNBC cells to antitumor agents, and is a promising indicator of disease outcomes in TNBC.

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Analysis of Rates of Brain Metastases and Association With Breast Cancer Subtypes in Ontario, Canada

Abstract: This cohort study describes clinical cumulative incidence of brain metastases among patients with de novo metastatic breast cancer using population health administrative databases in Ontario, Canada.

Cited by 11 publications

References 39 publications

The incidence of brain metastases in breast cancer according to molecular subtype and stage: a 10-year single institution analysis

The incidence of brain metastases in breast cancer according to molecular subtype and stage: a 10-year single institution analysis

BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non‐carriers: results from a rapid autopsy programme

PRR15 deficiency facilitates malignant progression by mediating PI3K/Akt signaling and predicts clinical prognosis in triple-negative rather than non-triple-negative breast cancer

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