Primary breast cancer phenotypes associated with propensity for central nervous system metastases

Abstract

BACKGROUND.There is anecdotal evidence that the incidence of central nervous system (CNS) metastases in breast cancer patients is increasing. It is unclear whether specific tumor biological properties or the use of systemic therapies influence this risk.METHODS.Using a database of 10,782 patients, 2685 patients were identified who experienced recurrence distantly. Clinical and biological features were analyzed in 2 ways: 1) patients who ever had versus those who never had CNS metastases, and 2) CNS metastases as the first site of recurrence versus those who had other sites. Correlations of survival after CNS metastasis with clinical and biologic features were also analyzed.RESULTS.In the ever versus never analysis, CNS metastases were significantly associated with younger age, premenopausal status, infiltrating ductal carcinoma histology (IDC), estrogen receptor (ER) and progesterone receptor (PR) negativity, low Bcl‐2, high S‐phase, aneuploidy, and altered p53. Tumor size, lymph node status, and use of adjuvant systemic therapy played little role. HER‐2 overexpression was not associated with an increased risk in these patients (none of whom were treated with trastuzumab) (P = .91). However, epidermal growth factor receptor (EGFR) overexpression was associated with increased risk (P = .02). A multivariate analysis revealed ER negativity (odds ratio [OR] 2.8, P<.001), IDC histology (OR 2.5, P = .02), and young age (P<.001) as independent factors for CNS metastases. The clinical and biologic profiles of primary tumors with CNS metastases at first recurrence did not differ from those with CNS metastases after recurrence to other sites, except for HER‐2 status. HER‐2‐positive tumors were not more likely to undergo recurrence initially in the CNS (P = .04). The median survival after CNS metastases was 5.5 months and HER‐2‐positive patients had a shorter survival.CONCLUSIONS.Younger patients with hormone receptor‐negative, highly proliferative, genomically unstable, and p53‐altered tumors were at increased relative risk for CNS metastases. HER‐2 expression and adjuvant systemic therapies did not increase this risk. Cancer 2006. © 2006 American Cancer Society.

Mystery of the brain metastatic disease in breast cancer patients: improved patient stratification, disease prediction and targeted prevention on the horizon?

“…Indeed, more recent study performed with 2136 metastatic breast cancer patients has confirmed that in contrast to premenopausal women, the postmenopausal ones are at lower risk of BM development (HR = 0.68, 95% CI 0.54-0.86, P = 0.001) [12]. The significance of this risk impacted by the menopausal status (P = 0.008) has been further confirmed by an independent study [10]. Thus, the premenopausal status at the time of BC diagnosis is considered as an additional risk factor for the brain metastatic lesions.…”

“…Likewise, the age younger than 35 years was proposed as the predictive factor for BM risks in another study that investigated 9524 breast cancer patients (P < 0.01) [9]. The explorative analysis that used the database containing information on 10,782 BC patients has identified a clear association of younger age of BC patients with a significantly higher prevalence of BM development (P < 0.001) [10]. Recorded cumulative incidence of BM was significantly higher for BC patients younger than 50 years (20.8%) compared to the older ones (9.7%) by observing follow-up during 5 years [11].…”

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

“…The risk factors for the development of brain relapse in general breast cancer patient populations include younger age, aggressive tumor growth, dissemination to other distant sites and steroid receptor negativity [18][19][20][21][22]. The knowledge of the risk factors for brain relapse in a subset of HER2-positive advanced breast cancer patients has been limited, and our study is among the few investigating this issue [23,24].…”

“…In this series the steroid receptor status and tumor grade were not related to the risk of brain relapse. The lack of steroid receptor expression is considered an adverse prognostic factor in general breast cancer population, and also includes increased risk of brain relapse [18][19][20][21][22]31]. The knowledge on the predictive value of steroid receptor status for brain metastases in HER2-positive advanced breast cancer patients is scarce.…”

“…It is hoped that determining tumor and host risk factors for brain metastasis might allow selection of candidates for preventive strategies. Most studies addressing risk factors for brain relapse included unselected breast cancer patients [18][19][20][21][22], whereas little is known on this issue in HER2-positive breast cancer patients [23,24]. In this study we assessed retrospectively the impact of selected clinical and pathological variables on the risk of brain relapse in a large, unselected group of patients with metastatic HER2-positive breast cancer.…”