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

Abstract

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.

Eribulin penetrates brain tumor tissue and prolongs survival of mice harboring intracerebral glioblastoma xenografts

“…This transfer most likely occurred because the BBB in the brain tumor tissue was at least partially disrupted, which would otherwise have prevented eribulin from entering the brain. In support of this, it has been reported that eribulin reduced the size of metastatic brain tumors developed from breast cancers, suggesting that eribulin penetrated intracerebral tumors in these cases …”

“…In support of this, it has been reported that eribulin reduced the size of metastatic brain tumors developed from breast cancers, suggesting that eribulin penetrated intracerebral tumors in these cases. [36][37][38] The most intriguing finding in our study was that the concentration of eribulin in the U87MG brain xenograft remained high even 24 hours after the injection (91.7 ± 35.0 nM), although its concentration in the plasma decreased below the detectable level ( Figure 4).…”

Comparison of IHC, FISH, ER and PR in Breast Cancer in Western Iran

“…Trastuzumab is a humanized monoclonal antibody directed against the HER2/neu oncoprotein and has the ability to inhibit tumor growth in breast cancer patients overexpressing HER2 [26].…”

Intracranial Metastatic Disease: Present Challenges, Future Opportunities

“…Notably, HER2-positive breast cancer patients treated with palliative chemotherapy and trastuzumab were more likely to develop BrM than patients who received palliative chemotherapy alone (37.8% vs. 25.0%, p=0.028); conversely, median time to death (TTD) measured from the development of IMD was significantly longer for patients treated with palliative chemotherapy and trastuzumab, compared to those treated with palliative chemotherapy alone (14.9 vs. 4.0 months, p=0.0005), suggesting that trastuzumab might exert some biological effect, even if partial, on IMD (101). Supporting this hypothesis, studies have similarly found that trastuzumab prolongs median OS in HER2-positive breast cancer patients with IMD (102)(103)(104).…”