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

Preliminary 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 = 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).

Figure 1. Kaplan–Meier Survival curve showing time for breast carcinoma to progress to brain metastases.

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 finding, if validated in larger studies, may alter treatment strategies for premenopausal patients with HER-2/neu-positive disease.