Treatment of Brain Metastases in HER2-positive Breast Cancer
Treatment of Brain Metastases in HER2-positive Breast Cancer
In recent years, brain metastases have emerged as a main challenge affecting the morbidity and mortality of patients with HER2-positive metastatic breast cancer. In the era following trastuzumab, approximately 30% of these patients develop brain metastases. Trastuzumab does not cross the blood–brain barrier, hence its role is limited to controlling extra-CNS metastases. Lapatinib emerged as a potential candidate; however, its use as a single agent was associated with modest responses. Combination with capecitabine was associated with good results, particularly in patients with newly diagnosed brain metastases. In this article, we discuss the role of trastuzumab and lapatinib in patients with HER2-positive breast cancer with brain metastases. We also highlight the complex structure of the blood–brain barrier and elucidate different potential strategies that could be useful in improving drug delivery.
Breast cancer (BC) is the second most common source of brain metastases (BM), being only preceded by lung cancer. The incidence of BM among patients with advanced BC is approximately 10–15% and reaches up to 30% in autopsy studies. Although treatment by whole-brain radiotherapy (WBRT) is associated with tumor regression and clinical improvement in the majority of patients, these responses are classically short-lived, ranging from 3 to 6 months. Historically, this was not a major challenge as progression in other visceral sites was the dominant source of mortality and thus, the development of novel strategies to manage BM was not considered of high priority. However, the introduction of novel chemotherapeutics and targeted agents has substantially prolonged survival of patients with metastatic disease, despite the fact that they have limited efficacy in dealing with BM. Therefore, there is a real concern that the incidence of BM will be more frequently encountered – given the improvement in survival – particularly in HER2-positive patients. Hence, BM could considerably impact survival at a time when many of these patients have extra-CNS disease control. In this article, we describe the different available systemic treatment strategies in managing BM in patients with HER2-positive BC. We also elaborate on potential approaches that we believe hold some promise in improving outcomes of such patients in the years to come.
Abstract and Introduction
Abstract
In recent years, brain metastases have emerged as a main challenge affecting the morbidity and mortality of patients with HER2-positive metastatic breast cancer. In the era following trastuzumab, approximately 30% of these patients develop brain metastases. Trastuzumab does not cross the blood–brain barrier, hence its role is limited to controlling extra-CNS metastases. Lapatinib emerged as a potential candidate; however, its use as a single agent was associated with modest responses. Combination with capecitabine was associated with good results, particularly in patients with newly diagnosed brain metastases. In this article, we discuss the role of trastuzumab and lapatinib in patients with HER2-positive breast cancer with brain metastases. We also highlight the complex structure of the blood–brain barrier and elucidate different potential strategies that could be useful in improving drug delivery.
Introduction
Breast cancer (BC) is the second most common source of brain metastases (BM), being only preceded by lung cancer. The incidence of BM among patients with advanced BC is approximately 10–15% and reaches up to 30% in autopsy studies. Although treatment by whole-brain radiotherapy (WBRT) is associated with tumor regression and clinical improvement in the majority of patients, these responses are classically short-lived, ranging from 3 to 6 months. Historically, this was not a major challenge as progression in other visceral sites was the dominant source of mortality and thus, the development of novel strategies to manage BM was not considered of high priority. However, the introduction of novel chemotherapeutics and targeted agents has substantially prolonged survival of patients with metastatic disease, despite the fact that they have limited efficacy in dealing with BM. Therefore, there is a real concern that the incidence of BM will be more frequently encountered – given the improvement in survival – particularly in HER2-positive patients. Hence, BM could considerably impact survival at a time when many of these patients have extra-CNS disease control. In this article, we describe the different available systemic treatment strategies in managing BM in patients with HER2-positive BC. We also elaborate on potential approaches that we believe hold some promise in improving outcomes of such patients in the years to come.
