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Purpose: Atypical ductal hyperplasia (ADH) is a high risk lesion with an increased risk of developing breast cancer. This study aims to identify factors predictive of malignant upgrade for ADH diagnosed on core needle biopsy (CNB) and to develop a nomogram to facilitate evidence-based decision making.Methods: Retrospective analysis of women with CNB diagnosed ADH at the National Cancer Centre Singapore between 2010 and 2015 was performed. Cox proportional hazards regression was used to identify independent clinical, radiological and histological factors associated with malignant upgrade. A nomogram was constructed and multivariable logistic regression coefficients were used to estimate the predicted probability of upgrade for each factor combination. Combinations with the lowest predicted probabilities (≤5%) were identified as low risk. Model sensitivity, specificity, positive and negative predictive values were assessed.Results: From 2010-2015, 238,122 women underwent screening under the national breast cancer screening programme. 29,564 women were recalled and 5742 CNBs were performed, of which 2686 were performed at NCCS. 88 patients (90 lesions) were diagnosed with ADH. 26 lesions were upgraded to a breast malignancy on excision biopsy. On univariate analysis, presence of a mass on either ultrasound (p= 0.018) or mammogram (p=0.026), presence of mammographic microcalcifications (p=0.047), diffuse microcalcification distribution (p=0.034), mammographic parenchymal density (p=0.008), presence of microcalcifications on biopsy (p=0.037) and three or more separate foci of ADH found on biopsy (p=0.024) were associated with malignant upgrade. Mammographic parenchymal density (Hazard ratio= 0.04, 95% CI 0.005-0.35, p=0.014), presence of a mass on ultrasound (Hazard ratio= 10.50, 95% CI 9.21-25.2, p=0.010) and number of foci of ADH (Hazard ratio = 1.877, 95% CI 1.831-1.920, p=0.002) remained significant on multivariate analysis and were included in the normogram which demonstrated good discrimination with C-statistic of 0.81 [95% CI, 0.74 to 0.88].Conclusion: Our model provides good discrimination of breast cancer risk prediction in patients with ADH on CNB. A subset of women at low risk (

The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit antimitotic drug-enforced mitotic arrest and “slip” into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence. It was found that cells postslippage entered senescence and could impart the senescence-associated secretory phenotype (SASP). SASP factor production elicited paracrine protumorigenic effects, such as migration, invasion, and vascularization. Both senescence and SASP factor development were found to be dependent on autophagy. Autophagy induction during mitotic slippage involved the autophagy activator AMPK and endoplasmic reticulum stress response protein PERK. Pharmacologic inhibition of autophagy or silencing of autophagy-related ATG5 led to a bypass of G1 arrest senescence, reduced SASP-associated paracrine tumorigenic effects, and increased DNA damage after S-phase entry with a concomitant increase in apoptosis. Consistent with this, the autophagy inhibitor chloroquine and microtubule-stabilizing drug paclitaxel synergistically inhibited tumor growth in mice. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment. Implications: Clinical regimens targeting senescence and SASP could provide a potential effective combinatorial strategy with antimitotic drugs. Mol Cancer Res; 16(11); 1625–40. ©2018 AACR.

The first nation-wide mammographic screening program in Asia, BreastScreen Singapore (BSS), was launched in Singapore in January 2002. This study compared the presentation and results of screen-detected breast cancers with symptomatic breast cancers in two affiliated high-volume institutions, one of which was an assessment centre for BSS. The medical records of patients diagnosed with primary breast cancer at the Department of General Surgery, Singapore General Hospital and the Department of Surgical Oncology, National Cancer Centre, Singapore, during the period January 2002 to December 2003 were reviewed. Clinical and pathological comparisons were made between screen-detected lesions and symptomatic lesions. Of a total of 767 cases, 640 (83.4%) were invasive carcinomas and 127 (16.6%) were ductal carcinoma in-situ (DCIS) lesions. Only 13.4% of them were screen-detected. Compared to symptomatic cancers, screen-detected lesions were of smaller size (median size 18 versus 23 mm), a lower stage (stages 0-2, 95 versus 83.2%) and histologic grade (grade 1-2, 71 versus 60%), with a higher incidence of DCIS (31.0 versus 14.3%) and had higher rates of breast conservation (45.6 versus 28.2%) (all p-values0.05). By multivariate analysis, tumor palpability, tumor size20 mm, nodal involvement, cerbB2 overexpression, and advanced disease stage were independent poor prognostic factors for disease-free survival, whereas nodal involvement, advanced disease, and recurrence predicted poor cancer-specific survival. However, there was no statistically significant difference in disease-free survival or cancer-specific survival between the two groups at a median follow-up of 38 months. Screening mammography has allowed the detection of smaller and hence oncologically more favorable lesions in Asian women. Although no significant survival benefit was demonstrated in our study, a longer period of follow-up is essential before the benefit of mortality reduction, as a result of mammography screening becomes evident in our population.

Summary: Purpose: The clinical utility of hippocampal volumetry is well documented, but the materials and techniques required to perform the procedure are not widely available outside major research centers. We describe a personal computer-based method of volumetric data analysis. Methods: Using a 1.0–T scanner, we obtained 2–mmthick tilted coronal MPRAGE magnetic resonance imaging (MRI) scans of 20 healthy volunteers aged 20–38 years. We used an inexpensive utility program to extract image information and an NIH Image for image analysis. The hippocampal formations were traced with a graphics tablet and landmarks described by Watson et al. (Neurology 1992;42:1743–50). Overlays of individual observers’ tracings were used to fine tune the selection of landmarks and boundaries. Filled-in silhouette pairs generated from these “training tracings” were compared to determine how well observers could visually quantify area differences. Results: Visual detection of asymmetry of silhouette pairs was sensitive, but the magnitude of asymmetry was underestimated. We achieved intraobserver coefficients of variation of right/left volume ratios between 0.82 and 3.16 and an interobserver range of volume ratios of 6%. In 20 healthy controls aged 20–38 years, the mean right and left hippocampal volumes were 2,911 mm3 and 2,836 mm3, respectively. The lower limits of normal were 2,217 mm3 for the right and 2,178 mm3 for the left. The mean right/left hippocampal ratio was 1.03, and the limits of normal (3 SD) for this were 0.95 to 1.10. Conclusions: Hippocampal volumetry can be performed reliably and economically. Our methodology makes it possible for different observers to generate consistent and comparable measurements.

Bronchioloalveolar carcinoma (BAC) is one of the few lung tumors known to demonstrate the air bronchogram sign. Production of this valuable radiologic sign by this tumor has been ascribed to an "alveolar" filling process in which tumor grows along alveolar walls with preservation of the architecture and secretes copious amounts of mucus. Thus, aerated bronchi are surrounded by alveoli that are filled with mucus and tumor. We present a case in which the air bronchogram sign and pulmonary consolidation are associated with a nonsecretory BAC. Alternative mechanisms that may produce the air bronchogram sign in BAC are offered.