Increased risk of brain metastases in patients with HER‐2/neu‐positive breast carcinoma

Abstract

P reliminary data have indicated that overexpression of HER-2/neu is correlated with more aggressive disease, an increased metastatic potential, and a poorer prognosis in patients with breast carcinoma. 1-3 Trastuzumab, a humanized anti-HER-2 antibody, reportedly is unable to penetrate the blood-brain-barrier and to our knowledge its efficacy in patients with brain metastases remains unclear. 4 -6 We conducted a retrospective study to evaluate whether patients with HER-2/neu-positive breast carcinoma have an increased risk of developing brain metastases.After approval from the institutional review board of West Virginia University, the pathology reports of 703 breast carcinoma patients who were diagnosed between April 1998 and January 2003 were reviewed. Based on immunohistochemistry or fluorescence in situ hybridization positivity, all patients who were positive for HER-2/neu were identified and their medical charts reviewed with regard to their course of disease and sites of metastases.Of the 703 patients studied, 164 (23%) were found to be positive for HER-2/neu; a sufficient oncologic history was available for 102 patients. Thirty-one patients (30%) developed distant metastases (95% confidence interval [95% CI], 0.223-0.399) during follow-up lasting a median of 57 months. Brain metastases were reported to have developed in 15 of these 31 patients (48%)(95% CI, 0.320 -0.652). A proportional hazards model was fit to the data to explore the association between patient age and time to the development of metastases. A significantly positive association (P ϭ 0.01) was found to exist between the two variables. Other models for censored data (Weibul, log-normal, and exponential models) were fitted and were found to produce nearly identical P values (Fig. 1).The results of this small retrospective study demonstrate that younger women with HER-2/neu-positive breast carcinoma may have a higher risk of developing brain metastases than previously reported for the general metastatic breast carcinoma patient population. This 442

The Effect of Early Detection of Occult Brain Metastases in HER2-Positive Breast Cancer Patients on Survival and Cause of Death

“…In HER2-positive breast cancer patients, brain metastases are significantly more common in women aged younger than 50 years (2,12,23,25,26), with visceral disease (1-4, 6, 7, 11, 17, 20, 26-28), with a good response to systemic treatment (4), with a short recurrence-free survival (26,27), and with cancers without expression of steroid receptors (11,12,14,27). In our series of HER2-positive breast cancer patients, visceral metastases have been confirmed as the only risk factor for brain metastases.…”

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

“…Several studies demonstrated increased risk of brain relapse in breast cancer patients with overexpressed or amplified HER2-neu gene [5][6][7][8]. HER2 abnormalities occur in 20-30% of invasive breast cancers and are associated with more aggressive tumor growth, increased risk of relapse and shorter survival [9,10].…”

Multifactorial central nervous system recurrence susceptibility in patients with HER2‐positive breast cancer

“…Furthermore, a series of retrospective studies has documented a CNS recurrence incidence of 25% to 40% with trastuzumab-based therapy for patients with HER2-positive metastatic breast cancer. [22][23][24][25][26][27][28][29][30] To our knowledge to date, there have been no largescale observational studies performed analyzing factors associated with CNS recurrence in a general population of newly diagnosed breast cancer patients with known HER2 status. The objective of the current study was to assess incidence, survival, and risk factors for CNS metastases in the incident breast cancer population systematically collected by the Parma Province Cancer Registry (PCR) over the 4-year period between 2004 and 2007.…”