Factors associated with the development of brain metastases

Hubbs, Jessica L.; Boyd, Jessamy A.; Hollis, Donna; Chino, Junzo; Saynak, Mert; Kelsey, Chris R.

doi:10.1002/cncr.25254

Cited by 120 publications

(60 citation statements)

References 55 publications

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“…In our series, on multivariate analysis, non-squamous cell cancer histology and LNR ≥ 30 % were associated with an increased risk of developing BM and BM as the first relapse. Non-squamous cell cancer as risk factor of BM and BM as the first relapse is consistent with many,[11,13-15,20,23,32-36] but not all,[7,8,10,12,19,22,31,37-39] previous studies.…”

Section: Discussionsupporting

confidence: 90%

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Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

et al. 2012

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BackgroundBrain metastases (BM) is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC) after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI) has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2) NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset.MethodsBetween 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM.ResultsFifty-three (24.4 %) patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001) and the ratio of metastatic to examined nodes or lymph node ratio (LNR) ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000) were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %.ConclusionsIn NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.

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Section: Discussionsupporting

confidence: 90%

“…Larger tumor size is associated with an increased risk of BM. [39] Bajard et al demonstrated that in a cohort of 305 stage I–IIIB patients, T4 was related with a higher risk of BM, compared with T1–3. [34] However, many other investigators did not find that T status was significantly related with the risk of BM.…”

Section: Discussionmentioning

confidence: 99%

Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

et al. 2012

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“…However, these special immunostaining markers are not used in routine pathological evaluation. Several recent studies evaluated LVI with routine HE staining and elastica-van Gieson staining, and demonstrated an association between LVI and disease recurrence [23,24,25,26,27]. The additional effect of the special immunostaining markers should be further validated in the future.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Lymphovascular Invasion for Patients with Stage I Non-Small Cell Lung Cancer

Hanagiri

Takenaka²,

Oka³

et al. 2011

Eur Surg Res

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Aims: This study retrospectively investigated the clinical significance of lymphovascular invasion (LVI) following a complete resection for stage I non-small cell lung cancer (NSCLC). Methods: A total of 226 patients who underwent a complete resection for pathological stage I NSCLC were examined. Results: Lymphatic invasion was pathologically diagnosed as ly0 in 156 patients, ly1 in 65, and ly2 in 5 patients. The pathological vascular invasion was diagnosed as v0 in 178 patients, v1 in 35, v2 in 10, and v3 in 3 patients. The 5-year survival rate after surgery of the patients with and without lymphatic invasion was 76.8 and 90.6%, respectively. There was a significantly more unfavorable prognosis in patients with lymphatic invasion (p = 0.042). The 5-year survival rate of the patients with vascular invasion was also significantly more unfavorable (67.8%) than that of patients without vascular invasion (90.4%; p = 0.004). LVI was found to significantly correlate with tumor size and the presence of pleural invasion. Conclusion: The LVI of NSCLC is a significant prognostic factor in patients with stage I tumors. In future clinical trials, it is necessary to evaluate the efficacy of adjuvant therapy for the selection of patients according to this criterion.

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“…As mentioned above, it has been shown that there is a 40% increase in EGFR expression in brain metastases compared to primary breast tumors (27). Additionally, non-small cell lung cancer (NSCLC) has a high frequency of activating EGFR gene alterations and a high incidence of metastasis to the brain (107–109). Considering these results it may indicate EGFR drives metastatic tumors toward the brain and/or the brain microenvironment and provides a selective pressure toward EGFR genetic alterations.…”

Section: Role Of Egfr In Breast Cancer Brain Metastasismentioning

confidence: 99%

EGFR and HER2 signaling in breast cancer brain metastasis

et al. 2016

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Breast cancer occurs in approximately 1 in 8 women and 1 in 37 women with breast cancer succumbed to the disease. Over the past decades, new diagnostic tools and treatments have substantially improved the prognosis of women with local diseases. However, women with metastatic disease still have a dismal prognosis without effective treatments. Among different molecular subtypes of breast cancer, the HER2-enriched and basal-like subtypes typically have higher rates of metastasis to the brain. Basal-like metastatic breast tumors frequently express EGFR. Consequently, HER2- and EGFR-targeted therapies are being used in the clinic and/or evaluated in clinical trials for treating breast cancer patients with brain metastases. In this review, we will first provide an overview of the HER2 and EGFR signaling pathways. The roles that EGFR and HER2 play in breast cancer metastasis to the brain will then be discussed. Finally, we will summarize the preclinical and clinical effects of EGFR- and HER2-targeted therapies on breast cancer metastasis.

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Factors associated with the development of brain metastases

Cited by 120 publications

References 55 publications

Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

Prognostic Significance of Lymphovascular Invasion for Patients with Stage I Non-Small Cell Lung Cancer

EGFR and HER2 signaling in breast cancer brain metastasis

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