Impact of Preoperative MRI in Invasive Ductal Carcinoma With Lobular Features on Core Biopsy.

BACKGROUND: Invasive breast cancer is comprised of a wide spectrum of histological types with different clinical presentations, imaging characteristics, and behaviors. Almost 10% of breast cancers with predominantly invasive ductal features have lobular components on core biopsy at primary diagnosis. Although the role of magnetic resonance imaging (MRI) in patients with purely lobular cancers is well-established, it is not clear if preoperative MRI is indicated in ductal cancer with lobular features. The aim of this study was to assess the role of preoperative MRI in patients with invasive ductal cancers with lobular features on core biopsy. MATERIALS AND METHODS: Data regarding patients with lobular features on core biopsy who underwent a preoperative MRI from January 2015 to December 2017 were retrospectively identified and analyzed. Imaging findings, additional investigations, and changes in treatment plans following the MRI scan were reviewed. RESULTS: The study included 120 patients, of whom 42 (35%) patients required a second-look ultrasound. Following a repeat ultrasound scan, 25 breasts and 4 axillae were biopsied. Thirty-eight percent of the breast biopsies and 50% of the axillary biopsies were malignant. Based on MRI findings, treatment plans changed in 22.5% of patients. MRI size was concordant with the histological size in 58.3% of cases, and MRI was accurate in 90% of patients in detecting multifocal disease requiring mastectomy. The majority of patients with changes in the management plans had mixed ductal and lobular cancer on final histology. CONCLUSION: This study has demonstrated that MRI picks up additional malignancies and changes management plans in patients with lobular features on core biopsy and should be considered in the preoperative workup.

Association of One-Step Nucleic Acid Amplification Detected Micrometastases with Tumour Biology and Adjuvant Chemotherapy.

One-step nucleic acid amplification (OSNA) is an intraoperative technique with a high sensitivity and specificity for sentinel node assessment. The aim of this study was to assess the impact of OSNA on micrometastases detection rates and use of adjuvant chemotherapy. A retrospective review of patients with sentinel node micrometastases over a five-year period was carried out and a comparison of micrometastases detection using OSNA and H&E techniques was made. Out of 1285 patients who underwent sentinel node (SLN) biopsy, 76 patients had micrometastases. Using H&E staining, 36 patients were detected with SLN micrometastases (9/year) in contrast to 40 patients in the OSNA year (40/year) (p < 0.0001), demonstrating a fourfold increase with the use of OSNA. In the OSNA group, there was also a proportional increase in Grade III, triple-negative, ER-negative, and HER-2-positive tumours being diagnosed with micrometastases. Also on interactive PREDICT tool, the number of patients with a predicted 10-year survival benefit of more than 3% with adjuvant chemotherapy increased from 52 to 70 percent. OSNA has resulted in an increased detection rate of micrometastases especially in patients with aggressive tumour biology. This increased the number of patients who had a predicted survival benefit from adjuvant chemotherapy.

A retinoid-related molecule that does not bind to classical retinoid receptors potently induces apoptosis in human prostate cancer cells through rapid caspase activation.

Synthetic retinoid-related molecules, such as N-(4-hydroxyphenyl)retinamide (fenretinide) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) induce apoptosis in a variety of malignant cells. The mechanism(s) of action of these compounds does not appear to involve retinoic acid receptors (RARs) and retinoid X receptors (RXRs), although some investigators disagree with this view. To clarify whether some retinoid-related molecules can induce apoptosis without involving RARs and/or RXRs, we used 4-[3-(1-heptyl-4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-oxo-E-propenyl] benzoic acid (AGN193198) that neither binds effectively to RARs and RXRs nor transactivates in RAR- and RXR-mediated reporter assays. AGN193198 potently induced apoptosis in prostate, breast, and gastrointestinal carcinoma cells and in leukemia cells. AGN193198 also abolished growth (by 50% at 130-332 nM) and induced apoptosis in primary cultures established from prostatic carcinoma (13 patients) and gastrointestinal carcinoma (1 patient). Apoptosis was induced rapidly, as indicated by mitochondrial depolarization and DNA fragmentation. Molecular events provoked by AGN193198 included activation of caspase-3, -8, -9, and -10 (by 4-6 h) and the production of BID/p15 (by 6 h). These findings show that caspase-mediated induction of apoptosis by AGN193198 is RAR/RXR-independent and suggest that this compound may be useful in the treatment of prostate cancer.

The prospects of retinoids in the treatment of prostate cancer.

Prostate cancer is the most prevalent cancer amongst males and accounts for 13% of cancer deaths in this population in the US. Aggressive, androgen-independent, metastatic prostate cancer is incurable, and the search for new therapies has been directed towards identifying agents that block proliferation and induce differentiation and/or apoptosis of prostate cancer cells. Retinoid receptor agonists, such as all- retinoic acid, can induce apoptosis of prostate cancer cells, but clinical studies have demonstrated only mild to moderate efficacy. Retinoic acid receptor antagonists are a new class of retinoids, and pre-clinical studies have shown that they potently inhibit the growth of prostate cancer cells and induce apoptosis. Here, we review whether retinoids have a role in the fight against prostate cancer.