Clinical Outcomes and Breast Cancer Subtypes in Patients with Brain Metastases

Kwon, Hyuk‐Chan; Oh, Sung Yong; Kim, Sung-Hyun; Lee, Suee; Kwon, Kee Hwan; Choi, Young–Jin; Cho, Goon-Jae; Kim, Yang-Soo; Lee, Miri; Lee, Jin Hwa; Kim, Dae Cheol; Lee, Hyung-Sik; Cho, Se Heon; Kim, Hyojin

doi:10.1159/000286281

Cited by 16 publications

(17 citation statements)

References 18 publications

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“…This study adds to the considerable available literature reporting that brain metastases from breast cancer are heterogeneous and differ in terms of tumor biology and prognosis. Previous studies have demonstrated that HER2‐positive disease is a favorable prognostic factor in patients with newly diagnosed brain metastases 7‐11. Our study suggests that HER2 positivity also has prognostic significance at the time of CNS recurrence.…”

Section: Discussionsupporting

confidence: 63%

“…Previous studies have demonstrated that HER2-positive disease is a favorable prognostic factor in patients with newly diagnosed brain metastases. [7][8][9][10][11] Our study suggests that HER2 positivity also has prognostic significance at the time of CNS recurrence. This is likely reflective of effective systemic therapy options in the HER2-positive population.…”

Section: Discussionmentioning

confidence: 58%

“…There has been increasing recognition that a predilection to CNS dissemination is influenced by breast cancer subtype, with HER2‐positive and triple‐negative tumors most likely to develop brain metastases 1‐6. Furthermore, tumor subtype has emerged as a prognostic factor for survival in breast cancer patients with newly diagnosed brain metastases 7‐11…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5][6] Furthermore, tumor subtype has emerged as a prognostic factor for survival in breast cancer patients with newly diagnosed brain metastases. [7][8][9][10][11] Selection of patients with brain metastases for treatment with stereotactic radiosurgery (SRS) and the timing of treatment are controversial. SRS may be used in the upfront setting without whole-brain radiation therapy (WBRT) in patients with a limited number of metastases; 2 randomized studies were unable to demonstrate a survival benefit with the addition of WBRT.…”

Section: Introductionmentioning

confidence: 99%

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Salvage stereotactic radiosurgery for breast cancer brain metastases

Kelly

Lin

Claus

et al. 2011

Cancer

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BACKGROUND: Salvage stereotactic radiosurgery (SRS) is often considered in breast cancer patients previously treated for brain metastases. The goal of this study was to analyze clinical outcomes and prognostic factors for survival in the salvage setting. METHODS: The authors retrospectively examined 79 consecutive breast cancer patients who received salvage SRS (interval of >3 months after initial therapy), 76 of whom (96%) received prior whole-brain radiation therapy. Overall survival (OS) and central nervous system (CNS) progression-free survival rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. RESULTS: Median age was 50.5 years. Fifty-eight percent of this population was estrogen receptor positive, 62% was HER2 positive, and 10% was triple negative. At the time of SRS, 95% had extracranial metastases, with 81% of extracranial metastases at other visceral sites (lung/pleura/liver). Forty-eight percent had stable extracranial disease. Median interval from initial brain metastases therapy to SRS was 8.4 months. Median CNS progression-free survival after SRS was 5.7 months (interquartile range [IQR], 3.6-11 months), and median OS was 9.8 months (IQR, 3.8-18 months). Eighty-two percent of evaluable patients received further systemic therapy after SRS. HER2 status (adjusted hazard ratio [HR], 2.4; P ¼ .008) and extracranial disease status (adjusted HR, 2.7; P ¼ .004) were significant prognostic factors for survival on multivariate analysis. CONCLUSIONS: In patients with good Karnofsky performance status, salvage SRS for breast cancer brain metastases is a reasonable treatment option, given an associated median survival in excess of 9 months. Furthermore, patients with HER2-positive tumors at diagnosis or stable extracranial disease at the time of SRS have an improved clinical course, with median survival of >1 year.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Salvage stereotactic radiosurgery for breast cancer brain metastases

Kelly

Lin

Claus

et al. 2011

Cancer

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“…5 Breast cancer brain metastasis is the main source of metastatic brain disease in women, 40 and has a high mortality rate as a result of resistance to chemotherapies 2 and a low success rate of radiotherapy. 41 …”

Section: Discussionmentioning

confidence: 99%

Neurotrophin-3 modulates breast cancer cells and the microenvironment to promote the growth of breast cancer brain metastasis

et al. 2012

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Metastasis, which remains incompletely characterized at the molecular and biochemical levels, is a highly specific process. Despite the ability of disseminated cancer cells to intravasate into distant tissues, it has been long recognized that only a limited subset of target organs develop clinically overt metastases. Therefore, subsequent adaptation of disseminated cancer cells to foreign tissue microenvironment determines the metastatic latency and tissue tropism of these cells. As a result, studying interactions between the disseminated cancer cells and the adjacent stromal cells will provide a better understanding of what constitutes a favorable or unfavorable microenvironment for disseminated cancer cells in a tissue-specific manner. Previously, we reported a protein signature of brain metastasis showing increased ability of brain metastatic breast cancer cells to counteract oxidative stress. In this study, we showed that another protein from the brain metastatic protein signature, neurotrophin-3 (NT-3), has a dual function of regulating the metastatic growth of metastatic breast cancer cells and reducing the activation of immune response in the brain. More importantly, increased NT-3 secretion in metastatic breast cancer cells results in a reversion of mesenchymal-like (EMT) state to epithelial-like (MET) state and vice versa. Ectopic expression of NT-3 in EMT-like breast cancer cells reduces their migratory ability and increases the expression of HER2 (human epidermal growth factor receptor 2) and E-cadherin at the cell–cell junction. In addition, both endogenous and ectopic expression of NT-3 reduced the number of fully activated cytotoxic microglia. In summary, NT-3 appears to promote growth of metastatic breast cancer cells in the brain by facilitating the re-epithelialization of metastatic breast cancer cells and downmodulating the cytotoxic response of microglia. Most importantly, our results provide new insights into the latency and development of central nervous system macrometastases in patients with HER2-positive breast tumors and provide mechanistic rationale to target HER2 signaling for HER2-positive breast cancer brain metastasis.

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