Risk Factors for Brain Metastases in HER2+ Breast Cancer Identified in Analysis

Patients with HER2-positive (HER2+) breast cancer are more likely to develop brain metastases based on when presence of metastases is diagnosed, postmenopausal status, treatment approach, and patient age, according to a study to be presented at the 2017 San Antonio Breast Cancer Symposium.

Breast cancer is the most common malignancy in women, and HER2+ breast cancer is the second leading cause of brain metastases after lung cancer. Prognosis for patients with breast cancer who develop brain metastases is poor. Therefore, researchers sought to determine the risk factors that indicate greater likelihood of this event occurring to establish more accurate screening for patients at risk.

In this retrospective analysis, researchers analyzed charts from 506 patients with HER2+ breast cancer (median age 52.7 years) treated at Institut Jules Bordet, Belgium, between 2000 and 2014. They reviewed the patients’ charts for disease characteristics, treatment regimens for primary and metastatic disease, and clinical outcomes. The researchers conducted statistical analyses with SAS 9.4 using Cox regression analyses, log-rank test, and Kaplan-Meier method.

Of the patients included in the analysis, 138 (27.3%) had metastatic breast cancer, 74 (14.6%) of whom had brain metastases. Twelve (8.7%) of the patients with metastatic disease had brain metastases as a first site of metastatic disease and 3 (2.2%) developed brain metastases as the only site of distant relapse. Median overall survival for patients with brain metastases was 1.74 years (range, 1 month to 3.2 years).

Risk factors for brain metastases in patients with HER+ breast cancer were metastatic disease at initial diagnosis (hazard ratio [HR] 4.46; P <.0001), postmenopausal status (HR 16.65; P <.0001), and adjuvant breast radiotherapy (HR 1.79; P =.0198). Risk factors for brain metastases at the time-point of metastatic disease were postmenopausal status (HR 1.90; P =.0464), the presence of lung metastases (HR 2.61; P =.0004), an interval of more than 1 year between initial breast cancer diagnosis and development of metastatic disease (HR 1.91; P =.0179), and age younger than 40 years (HR 1.78; P =.0353).

Biological factors such as hormone receptor status, degree of HER2 amplification, and tumor grade did not affect the likelihood of developing brain metastases. The type of systemic treatment in either the adjuvant or metastatic setting (chemotherapy, anti-HER2 treatment) also did not affect patients’ risk.

Use of local treatment (surgery, stereotactic radiosurgery [SRS], or whole brain radiotherapy [WBRT]) with anti-HER2–directed therapy as first-line therapy for brain metastases was associated with more pronounced improved overall survival in patients treated with tyrosine kinase inhibitors (HR 0.13; 95% CI, 0.05-0.33; P <.0001) vs those treated with trastuzumab and/or pertuzumab (HR 0.53; 95% CI 0.24-1.15; P =.1085).

Although no current imaging screening recommendations are established for this patient population, the researchers report that surgery and SRS are associated with improved overall survival and/or less cognitive impairment compared with WBRT. However, these treatment options are limited to patients with less extensive brain metastases. The researchers suggest that “[i]n this context, randomized trials examining the role of MRI screening for brain metastases in metastatic HER2+ breast cancer with high risk features are warranted.”

Reference

Maurer C, Tulpin L, Dumitrescu C, et al. Risk factors for the development of brain metastases (BM) in 506 patients with HER2-positive breast cancer (HER2+ BC): a single institutional retrospective analysis. Poster presentation at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX.