Metabolomics patterns of breast cancer tumors using mass spectrometry imaging.

PURPOSE: Intraoperative assessment of surgical margins is important for reducing the rate of revisions in breast conserving surgery for palpable malignant tumors. The hypothesis was that metabolomics methods, based on mass spectrometry, could find patterns of relative abundances of molecules that distinguish clusters of benign tissue and cancer in surgical resections. METHODS: Excisions from 8 patients were used to acquire 112,317 mass spectrometry signals by desorption electrospray ionization. A process of nonnegative matrix factorization and graph decomposition produced clusters that were approximated as affine spaces. Each signal's distance to the affine space of a cluster was used to visualize the clustering. RESULTS: The distance maps were superior to binary clustering in identifying cancer regions. They were particularly effective at finding cancer regions that were discontinuously distributed within benign tissue. CONCLUSIONS: Desorption electrospray ionization mass spectrometry, which has been shown to be useful intraoperatively, can acquire signals that distinguish malignant from benign breast tissue in surgically excised tumors. The method may be suitable for real-time surgical decisions based on cancer margins.

Biology of bone metastases.

BACKGROUND: Bone metastases cause morbidity and mortality in multiple malignancies. In addition to portending a dire prognosis, bone metastases cause bone pain, fractures, hypercalcemia, spinal cord compression, and other nerve compression syndromes. Improved understanding of the mechanisms that predispose tumor metastases to bone is needed to improve patients' therapeutic options, maintain their quality of life, and improve their survival. METHODS: This review discusses selected preclinical and clinical data regarding bone metastasis development and cytokine/molecular interactions predisposing to bone metastases formation. Potential interventions for reducing bone metastases are also described. RESULTS: Biologic mechanisms resulting in metastases of tumor cells to bone are being studied. Among these are the RANKL pathway, osteoclast activation via cytokines (produced by tumor cell and cells in the bone microenvironment), interactions with transient and stromal cells in the bone microenvironment, and molecules such as PTHrP and endothelin-1. These molecules offer important opportunities for targeted interventions to decrease bone metastases-associated morbidity. CONCLUSIONS: Knowledge of the pathophysiology of bone and cancer is developing rapidly. Relationships among cancer cells, bone-derived cells, and cytokines provide opportunities for the development of new interventions. Therapy targeting osteoclast/osteoblast interactions has proven benefit for patients with bone metastases.

Age and survival estimates in patients who have node-negative T1ab breast cancer by breast cancer subtype.

AIM: This article evaluates the risk of recurrence for patients who have small node-negative breast cancer by age and tumor subtype. METHODS: One thousand twelve patients with a T1a,bN0 breast cancer diagnosed between 1990 and 2002 who did not receive chemotherapy or trastuzumab were included. Patients and tumor characteristics were compared using the χ(2) or Wilcoxon's rank sum tests. Survival outcomes were estimated with the Kaplan-Meier method and compared using the log-rank statistic. Cox proportional hazards models were used to determine association of breast cancer subtypes and age at diagnosis with other covariates. RESULTS: Median age was 51.5 years. There were 771 hormone receptor (HR)-positive, 98 HER2-positive, and 143 triple-negative breast cancers (TNBC). Six hundred ninety-three patients were > 50 years, and 33 patients were ≤ 35 years. For 5-year survival estimates, there were 118 deaths and overall survival was 94.6% (95% confidence interval [CI] = 93.2%, 96.1%). After adjusting for breast cancer subtype and other tumor characteristics, patients ≤ 35 had 2.51 (95% CI = 1.21-5.22) times greater risk of worse recurrence-free survival (RFS), and 2.60 (95% CI = 1.05-6.46) times greater risk of worse distant RFS (DRFS) compared to patients > 50 years old. Compared to patients with HR-positive disease, patients with HER2-positive breast cancer had 4.98 (95% CI = 2.91-8.53) times the risk of worse RFS and 4.70 (95% CI = 2.51-8.79) times greater risk of worse DRFS, and patients with TNBC had 2.71 (95% CI = 1.59-4.59) times greater risk of worse RFS and 2.08 (95% CI = 1.04-4.17) times greater risk of worse DRFS. CONCLUSIONS: In this cohort, patients with T1a,bN0 breast cancer, young age and breast cancer subtype were significantly associated with RFS and DRFS.