Risk factors for brain relapse in HER2-positive metastatic breast cancer patients

Duchnowska, Renata; Dziadziuszko, Rafał; Czartoryska-Arłukowicz, Bogumiła; Radecka, Barbara; Szostakiewicz, Barbara; Sosińska-Mielcarek, Katarzyna; Karpińska, Agnieszka; Starosławska, Elżbieta; Kubiatowski, Tomasz; Szczylik, Cezary

doi:10.1007/s10549-008-0275-z

Cited by 45 publications

(29 citation statements)

References 43 publications

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“…A positive HER2 status in primary breast cancer was considered a risk factor for the development of brain metastases (22). Although trastuzumab does not cross the blood-brain barrier (BBB) and has no direct activity on brain metastases, previous studies reported a survival benefit with trastuzumab in HER2-positive patients with brain metastases, who had a significantly longer survival compared to that of HER2-negative patients (17)(18)(19)(20)(21), which was consistent with our findings.…”

Section: Discussionsupporting

confidence: 91%

Extended trastuzumab therapy improves the survival of HER2-positive breast cancer patients following surgery and radiotherapy for brain metastases

Okita

Narita²,

Suzuki

et al. 2013

Molecular and Clinical Oncology

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Abstract. Brain metastases usually present late during the course of breast cancer and are associated with an unfavorable prognosis. It was previously demonstrated that the status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2) may be altered in the time window between the emergence of the primary breast tumor and the development of metastases. The aim of this study was to compare the expression of ER, PR and HER2 in pathology samples of primary breast cancer and brain metastases in order to evaluate whether previously administered therapy was able to modify this status and determine whether biomarker alterations affect prognosis after the development of brain metastases. Data were collected from 62 patients who were initially diagnosed with breast cancer that had metastasized to the brain. The ER, PR and HER2 status of the samples from the primary tumors and the brain metastases was determined. Differences in the immunohistochemical profiles of ER, PR or HER2 between the primary tumors and the brain metastases in 17 patients (29.3%) were identified. The patients with HER2-positive brain metastases who received trastuzumab had no leptomeningeal metastases and exhibited a longer survival time after brain metastases compared to the HER2-positive patients who did not receive trastuzumab and the patients with HER2-negative brain metastases (P=0.0005). Our results suggested that the patients treated with trastuzumab following surgery and radiotherapy for brain metastases exhibited a better prognosis. Thus, the HER2 status in brain metastases requires re-evaluation and extended trastuzumab therapy is recommended after brain metastases.

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Section: Discussionsupporting

confidence: 91%

Extended trastuzumab therapy improves the survival of HER2-positive breast cancer patients following surgery and radiotherapy for brain metastases

Okita

Narita²,

Suzuki

et al. 2013

Molecular and Clinical Oncology

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“…Trastuzumab, a standard treatment agent for HER2-positive patients, is known to have little activity for reducing intracranial lesions due to poor BBB permeability. Previous studies have indicated that treatment with trastuzumab was not associated with incidence of BM [23,24], and survival after BM development was significantly longer in patients with trastuzumab than those without trastuzumab [11,25,26]. Trastuzumab combined with chemotherapy may favorably affect systemic metastatic lesions, probably leading to better systemic control and improved outcome of HER2-positive patients after BM development.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Factors Related to the Prognosis of Metastatic Breast Cancer Patients after Development of Brain Metastasis

et al. 2015

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Background: The prognosis of breast cancer patients with brain metastasis (BM) is extremely poor, and the survival after development of BM is very short. We aimed to investigate clinicopathological factors related to significant effects on the prognosis after BM development. Patients and Methods: This is a retrospective study of 75 early breast cancer patients who received the standard of care and subsequently developed BM. Results: Breast cancer subtype was one of the significant predictors for prognosis after BM diagnosis. Luminal HER2 patients had the most favorable prognosis after BM diagnosis (p = 0.011). Favorable performance status (PS) at BM diagnosis (p < 0.001) and a single metastatic brain tumor (p = 0.032) were significantly associated with good prognosis after BM diagnosis. Metastatic time courses of the patients was found not to be significantly associated with survival after BM diagnosis. Univariate and multivariate analysis indicated that luminal HER2 cancer, favorable PS at BM diagnosis, and a single metastatic brain tumor were the independent prognostic factors for survival after BM development, making a decisive influence on local or systemic control. Conclusion: Appropriate treatments for tumor subtypes and to improve the general condition of patients would result in improved outcomes for the patients with BM.

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“…A number of patient and tumor characteristics, including younger age (premenopausal or \50 years) [17], the presence of lung or liver metastases [17], negative hormonereceptor (HR) status [18], larger tumor size [19,20], larger number of involved lymph nodes [20,21], and positivity for human epidermal growth factor receptor 2 (HER2) [19,22], have been identified as risk factors for developing BM [18,20,21,[23][24][25]. Regarding the relationship between HER2 status and the incidence of BM, patients with HER2-positive breast cancer are at risk of developing BM, with cumulative incidence as high as 30-50% [17,22,24,26,27].…”

Section: Risk Factors Of Developing Bm Among Patients With Breast Cancermentioning

confidence: 99%

“…Regarding the relationship between HER2 status and the incidence of BM, patients with HER2-positive breast cancer are at risk of developing BM, with cumulative incidence as high as 30-50% [17,22,24,26,27]. Duchnowska et al [22] reported that the median time from treatment of the primary tumor to brain relapse for HER2-positive patients was 15 months, which is much shorter than that for all breast cancer patients [2,13], and the cumulative 1-year, 3-year, and 5-year risks for those patients were 17, 42, and 55% respectively [22]. This trend of shorter duration until the development of BM in HER2-positive compared with HER2-negative patients was confirmed in another series [28].…”

Section: Risk Factors Of Developing Bm Among Patients With Breast Cancermentioning

confidence: 99%

Radiation therapy for brain metastases in breast cancer patients

Aoyama

2010

Breast Cancer

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Most randomized comparison trials (RCTs) investigating treatments for brain metastases (BM) have included BM from any origin; as a result, more than half (52.4-77.0%) of the BM in these trials originated from the lungs (mostly non-small-cell lung cancer, NSCLC), with the breasts being the origin in only 6.8-19.0% of cases. In addition, patients with poor systemic status (KPS \ 70) were not included in these trials. Hence, before we can apply RCT-based information to the daily clinical treatment of BM from breast cancers, it will be crucial to differentiate the characteristics of BM originating from NSCLC and BM originating from breast cancer. Although stereotactic radiosurgery (SRS) is widely used in Japan, level-1 evidence suggests that the benefit of using SRS in addition to whole-brain radiation therapy (WBRT) has been proven only for patients with a single BM. Treatment with SRS alone, which is widely used in Japan, seems attractive because it could avoid the risk of long-term adverse effects of WBRT. However, level-1 evidence suggests that the omission of WBRT results in a high frequency of brain tumor recurrence (BTR). In an RCT between SRS-alone and SRS ? WBRT conducted in Japan, we found that patients who had a single BM and no extracranial metastases had a low risk of developing BTR after initial brain management (low-risk group) compared with those who had 2 or more BM and extracranial metastases (high-risk group). In order to meet the criteria of ''low-risk'' BTR, patients also should have good systemic status (KPS 3 70). Epidemiologic data suggest that the prognosis is twice as likely to be poor in patients with BM from breast cancer (RPA III = KPS \ 70) than in patients with BM from NSCLC (40 vs. 20%); in addition, the probability of brain-only metastases in patients with breast cancer is less than half that in patients with NSCLC (20-25 vs. 60-75%). Considering these findings, we should be aware that most patients with BM from breast cancer are not good candidates for SRS alone, and, therefore, the role of WBRT is still important in the era of modern radiation techniques.

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Risk factors for brain relapse in HER2-positive metastatic breast cancer patients

Cited by 45 publications

References 43 publications

Extended trastuzumab therapy improves the survival of HER2-positive breast cancer patients following surgery and radiotherapy for brain metastases

Extended trastuzumab therapy improves the survival of HER2-positive breast cancer patients following surgery and radiotherapy for brain metastases

Clinicopathological Factors Related to the Prognosis of Metastatic Breast Cancer Patients after Development of Brain Metastasis

Radiation therapy for brain metastases in breast cancer patients

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