Surgical upgrade rate of breast atypia to malignancy: An academic center's experience and validation of a predictive model.

Atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) are commonly seen on breast core needle biopsy (CNB). Many institutions recommend excision of these lesions to exclude malignancy. A retrospective chart review was performed on patients who had ADH, ALH, or LCIS on breast CNB from 1/1/08 to 12/31/10 who subsequently had surgical excision of the biopsy site. Study objectives included determining upgrade to malignancy at surgical excision, identification of predictors of upgrade, and validation of a recently published predictive model. Clinical and demographic factors, pathology, characteristics of the biopsy procedure and visible residual lesion were recorded. T test and chi-squared test were used to identify predictors. Classification tree was used to predict upgrade. 151 patients had mean age of 53 years. The mean maximum lesion size on imaging was 11 mm. The primary atypia was ADH in 63.6%, ALH in 27.8%, and LCIS in 8.6%. 16.6% of patients had upgrade to malignancy, with 72% DCIS and 28% invasive carcinoma. Risk factors for upgrade included maximum lesion size (P = .002) and radiographic presence of residual lesion (P = .001). A predictive model based on these factors had sensitivity 78%, specificity 80% and AUC = 0.88. Validating a published nomogram with our data produced accuracy figures (AUC = 0.65) within published CI of 0.63-0.82. In CNB specimens containing ADH, ALH, or LCIS, initial lesion size and presence of residual lesion are predictors of upgrade to malignancy. A validated model may be helpful in developing patient management strategies.

Role of imaging in neoadjuvant therapy for breast cancer.

Neoadjuvant chemotherapy (NAC) involves administration of chemotherapeutic agents to patients with newly diagnosed breast cancer prior to definitive surgical treatment. Assessment of disease response to chemotherapeutic agents in vivo prior to any surgical intervention is necessary as medical oncologists are commonly tailoring or changing therapy during NAC based on response. It can also maximize the pathologic complete response (pCR) rate, resulting in more women undergoing breast conservation rather than mastectomy. Although some studies show a pCR to NAC in only 13-26 % of women, recent studies have shown higher pCR rates, especially for HER2-positive disease treated with targeted anti-HER2 therapy. Thus, accurate imaging tools for quantifying disease response are critical in the evaluation and management of patients undergoing NAC. There is currently no standard imaging method for monitoring response to therapy. Response to therapy tends to vary by tumor subtype and can be accurately assessed on imaging. We review the role of imaging before and after neoadjuvant therapy and discuss the advantages and limitations of currently available modalities, including mammography, ultrasonography, magnetic resonance imaging, and nuclear imaging.

Nonmass enhancement on breast MRI: review of patterns with radiologic-pathologic correlation and discussion of management.

OBJECTIVE: The purpose of this article is to review the varied appearances and associated diagnoses of nonmass enhancement on breast MRI with radiologic-pathologic correlation. CONCLUSION: Knowledge of the distribution and internal characteristics of these findings is helpful to determine when core needle biopsy is indicated. Correlating imaging with pathologic findings is critical in making appropriate recommendations regarding clinical management.

Carbogen gas-challenge BOLD MR imaging in a rat model of diethylnitrosamine-induced liver fibrosis.

PURPOSE: To investigate the relationship between gas-challenge blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging measurements and hepatic disease progression in a rat model of diethylnitrosamine (DEN)-induced liver fibrosis. MATERIALS AND METHODS: The institutional animal care and use committee approved all experiments. Liver fibrosis was induced in 27 male Wistar rats by means of weekly oral gavage with 5 mL of 1.5% DEN solution per kilogram of body weight for 3-11 weeks, which produced varying degrees of liver fibrosis. Eight rats developed nonsubstantial fibrosis; eight rats, substantial fibrosis; and 15 rats, cirrhosis. Four nontreated healthy rats served as controls. Multiple-gradient-echo MR images were acquired in the rats at steady-state normoxia and hyperoxia and then during dynamic gas challenges. The change in R2* (DeltaR2*) during the gas challenge and the ratio of number of activated voxels to total number of voxels in the liver were quantified. Masson trichrome staining of liver tissue was used to identify collagen tissue. Liver fibrosis was assessed by using a semiquantitative METAVIR scoring system and quantitative analysis of the percentage of liver fibrosis. Hepatic hemodynamic responses at BOLD MR imaging were compared across the fibrosis stages at independent-sample t test and linear regression analyses. RESULTS: DeltaR2* was well correlated with gas-challenge interval. Mean DeltaR2* decreased during liver fibrosis progression, from 19.60 sec(-1) +/- 4.47 (standard deviation) in animals without substantial fibrosis to 14.02 sec(-1) +/- 2.88 and 6.26 sec(-1) +/- 7.40 in animals with substantial fibrosis and cirrhosis, respectively (P = .006 for rats without vs rats with substantial fibrosis, P = .001 for rats with substantial fibrosis vs rats with cirrhosis, P < .001 for rats without substantial fibrosis vs rats with cirrhosis). Mean DeltaR2* (r = -0.773) and liver activation (r = -0.691) were inversely correlated with liver fibrosis (P < .001). CONCLUSION: Carbogen gas-challenge BOLD MR imaging can depict hepatic hemodynamic alterations during the progression of fibrosis and has the potential to serve as a noninvasive, nonenhanced imaging method for liver fibrosis diagnosis and staging.

Cytoarchitecture of fibroblast growth factor receptor 2 (FGFR-2) immunoreactivity in astrocytes of neurogenic and non-neurogenic regions of the young adult and aged rat brain.

Fibroblast growth factors (FGFs) are polypeptides that exert diverse biological effects on many cell types and tissues during embryogenesis and adulthood. In the adult brain, FGF-2 is primarily expressed by astrocytes and select groups of neurons. It has been shown that FGF-2 is neuroprotective and can stimulate proliferation of NSCs in neurogenic regions of the adult mammalian brain. Cellular responses to FGFs are mediated through membrane-spanning tyrosine kinase receptors in conjunction with low affinity binding to heparin sulfate proteoglycans. Four FGF receptors (FGFR1-4) have been cloned and characterized to date. In this study, we describe the anatomical distribution of FGFR-2 in young and aged rat brains. We demonstrate that the olfactory bulb, hippocampus, and cerebellum display the most robust FGFR-2 expression and observed age-related decrease in FGFR-2 levels in some but not all brain regions. In addition, we identified astrocytes as the primary source of FGFR-2 expression using immunofluorescence confocal microscopy. The astrocyte populations in the neurogenic areas, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus, express high levels of FGFR-2 protein, which points to its possible involvement in neurogenesis. We also explored the role of FGFR-2 in response to perforant pathway lesion and observed enhanced FGFR-2 expression by astrocytes surrounding the lesion. Thus, FGF-2 biological effects on astrocytes appear to be mediated through FGFR-2-dependent mechanisms, and this may provide an indirect route by which FGF-2 acts on neuronal populations.

Do breast arterial calcifications on mammography predict elevated risk of coronary artery disease?

PURPOSE: To determine whether breast arterial calcifications (BAC) seen on mammography correlates with coronary artery calcium score on coronary CT as it may serve as a potential marker for increased risk of developing symptomatic coronary artery disease (CAD). MATERIALS AND METHODS: Retrospective review of the imaging database at our institution identified 145 female patients who underwent coronary CT within a year of screening or diagnostic mammography. The coronary calcium score on CT was calculated by multiplying area of calcification by weighted value assigned to its highest Hounsfield unit and summed for all lesions and expressed as Agaston score. Calculated scores were risk stratified for developing CAD as follows: 0-no risk; 1-10-minimal; 11-100-mild; 101-400-moderate; >400-high risk. Percentile distribution of calcium score adjusted by age, gender and race was calculated based on results of the Multi-Ethnic Study of Atherosclerosis (MESA), which excluded patient with diabetes and chronic renal disease. The mammograms were reviewed by MQSA-certified breast radiologists who were blinded to patients' coronary calcium scores. Mammograms were interpreted for presence or absence of BAC. The calcium scores and corresponding percentiles were correlated with BAC on mammography. Cardiac risk factors such as, diabetes, hypertension, hyperlipidemia, family history of CAD and smoking, were recorded for each patient. RESULTS: BAC correlated with coronary calcium score of >11 (p=0.0001), corresponding to mild or greater risk of developing CAD. Specifically, coronary calcium score of >11 was seen in 68% (25/37) of patients with BAC and 31% (34/108) of patients without BAC. Accounting for race, gender and age, presence of BAC showed statistically significant correlation with percentile scores of >25. Namely, 70.4% (19/27) of patients with BAC vs. 44.6% (41/92) of patient without BAC showed percentile score of >25 for developing CAD. Statistically significant association was observed of BAC with diabetes (p=0.01) and chronic renal disease (p=0.005). BAC showed no significant associated with hyperlipidemia, hypertension, smoking and family history of CAD. CONCLUSION: BAC does predict coronary artery calcium score of >11, which indicates mild or greater risk of developing CAD. In addition, statistically significant correlation exists between BAC and cardiac risk factors, namely diabetes and chronic renal disease. Our study suggests that BAC on mammography can be utilized as a potential marker for increased risk of developing CAD.