Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases☆
Introduction
Breast cancer (BC) is the second most common solid malignancy that spreads to the brain.1 Historical data suggest an incidence of symptomatic cerebral metastases (CM) in BC patients between 5% and 16%2, 3; autopsy studies revealed an even higher incidence of up to 34%.1, 2, 4 Patients suffering from symptomatic CM have a poor prognosis with a median survival time after diagnosis ranging between 3 and 9 months.5, 6 Early onset BC, HER2-overexpression, high tumour grade and oestrogen receptor (ER) negativity have been described as independent risk factors for development of CM.5, 7, 8, 9, 10
In past years, carcinomas of the breast have been classified into six subgroups based on gene expression patterns, each subgroup showing a different clinical outcome. Patients with tumours bearing the basal-like subtype showed the shortest overall survival.11 Triple-negative BC (oestrogen receptor negative (ER-), progesterone receptor negative (PR-) and HER2-negative (HER2-)) specimens exhibit the basal-like phenotype in 91% of all cases and, therefore, triple negativity can be used as a clinical surrogate for the genotypically defined basal-like phenotype.12 As mentioned above, HER2-overexpression is associated with a more aggressive course of disease.13 According to ER status, HER2-overexpressing BC can be classified into two subgroups: the HER2 subtype (ER-negative) and the Luminal B subtype (ER-positive).14
The goals of our study were (1) to determine the incidence of CM in a large cohort of patients with BC, (2) to evaluate the influence of BC subtypes (specifically triple negativity and HER2-overexpression) and other risk factors on the development of CM, and (3) to analyse the clinical course of patients with CM in BC.
Section snippets
Patients and methods
The data for this exploratory analysis were derived from the prospectively running clinical tumour registry of our EUSOMA (European Society of Breast Cancer Specialists) breast cancer unit at a city hospital (Dr. Horst Schmidt Kliniken) in Wiesbaden, Germany. The tumour registry data from BC patients included tumour characteristics, modalities and outcomes of treatments, which are updated annually by the registry physician. The follow-up information is also updated at least annually, either
Patients’ characteristics
The final study cohort consisted of 2441 patients with primary invasive BC. Of those, 284 (11.6%) patients had triple-negative BC, 245 (10.1%) showed HER2-positive phenotypes and 1912 (78.3%) patients expressed SR+/HER2- phenotypes.
Patient characteristics are displayed in Table 1. Statistically significant differences among the three groups were seen regarding age at BC diagnosis, size of the primary tumour, lymph-node involvement and grading. Patients with triple-negative and HER2-positive BC
Discussion
This retrospective, single-institution study analysing the risk factors for development of brain metastases was based on a relatively large population with 2441 patients with invasive BC. Although some related studies were conducted on a larger cohort,15, 16 other comparable analyses were done on a smaller scale.17, 18, 19
The frequency of symptomatic CM has been reported to be between 5 and 16%,2, 3 and in asymptomatic patients even up to 34%.1, 10, 20 A higher incidence of symptomatic brain
Conflict of interest statement
None declared.
Acknowledgement
We thank Dr. S. Yu-Poth, Dr. M. Kandel and Dr. V. Stinshoff who provided valuable support regarding manuscript reading and language improvement.
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This manuscript was partially presented orally at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago 2008.