Nomogram to Predict Subsequent Brain Metastasis in Patients With Metastatic Breast Cancer

Abstract

PURPOSE Brain metastasis is usually a fatal event in patients with stage IV breast cancer. We hypothesized that its occurrence can be predicted if a clinical nomogram can be developed, thus allowing for selection of enriched patient populations for prevention trials. PATIENTS AND METHODS Electronic medical records of patients with metastatic breast cancer were retrospectively reviewed for the period between January 2000 and February 2007 under a study approved by the institutional review board. A multivariate logistic regression analysis of selected prognostic features was done. A nomogram to predict brain metastasis was constructed and validated in a cohort of 128 patients with brain metastasis treated at the Cross Cancer Institute (Edmonton, Alberta, Canada). Results Of 2,136 patients with breast cancer, 362 developed subsequent brain metastasis. Age, grade, negative status of estrogen receptor and human epidermal growth factor receptor 2, number of metastatic sites (one v > one), and short disease-free survival were significantly and independently associated with subsequent brain metastasis. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.68 (95% CI, 0.66 to 0.69) in the training set. The validation set showed a good discrimination with an AUC of 0.74 (95% CI, 0.70 to 0.79). The nomogram was well calibrated, with no significant difference between the predicted and the observed probabilities. CONCLUSION We have developed a robust tool that is able to predict subsequent brain metastasis in patients with breast cancer with nonbrain metastatic disease. Selection of an enriched patient population at high risk for brain metastasis will facilitate the design of trials aiming at its prevention.

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

“…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]. A series of independent studies which differed from each other by experimental design and patient subgroups involved, have, nevertheless, confirmed these main findings [12,13], namely:…”

“…Hence, premenopausal women sustainably demonstrate higher cumulative risks for BM development during the 5 years (3.8 vs. 2.8%), 10 years (6.2 vs. 4.2%), and 15 years (7.1 vs. 4.6%) of the follow-up observations performed after the initial BC has been diagnosed (P < 0.01) [9]. 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].…”

“…To this end, summarised BC breast cancer, BM brain metastases, HR hazard ratio, ER/PR oestrogen/progesterone receptors, HER2 human epidermal growth factor-2, COX2 cyclooxygenase-2, HBEGF epidermal growth factor receptor ligand, ST6GALNAC5 α2,6-sialyltransferase information is presented in Table 1. Multi-parametric models assessing BM risks are currently under consideration [12]. Further, the multi-parametric prognostic tools for the optimised BM treatment algorithms, disease and therapy monitoring are under development [69][70][71].…”

Antidepressant use and risk of central nervous system metastasis

“…Patients with lung metastasis also developed brain metastasis more frequently than those patients without lung metastasis [153,216,232]. Graesslin et al [233] developed a nomogram to predict brain metastasis in patients with metastatic breast cancer; significant predictors include younger age, higher histological grade, number of metastatic sites, short disease-free survival, and HER2 positivity.…”

Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer.

“…Lin et al (16) reported that nearly 46% of women with metastatic TNBC developed brain metastasis that was associated with a median survival time of 4.9 months. Robust nomograms have also been developed that can help risk stratify women with metastatic breast cancer helping to identify groups most likely to develop brain metastases (18). However, with the relatively high overall incidence of brain metastases and the associated poor survival following its diagnosis among women with TNBC, a more practical and clinically meaningful research direction would be to identify groups of women with early stage TNBC who are at high risk of developing brain metastases.…”