A component of lobular carcinoma in clinically lymph node-negative patients predicts for an increased likelihood of upstaging to pathologic stage III breast cancer.

PURPOSE: Physical examination and diagnostic imaging are often less precise in determining the extent of disease in invasive lobular carcinoma (ILC) relative to nonlobular histologies. Anecdotally, surgical axillary evaluation frequently reveals positive lymph nodes in clinically N0 patients with ILC; however, few studies quantify the likelihood of finding unsuspected disease at the time of surgery. In this study, we evaluate whether the presence of lobular histology increases the incidence of surgical upstaging to pathologic stage IIIA or greater in patients with a clinically node-negative axilla and positive sentinel lymph node (SLN) biopsy. METHODS AND MATERIALS: We examined patients from our institution between 1997 and 2009 treated specifically with mastectomy, SLN biopsy, and completion axillary lymph node dissection due to a positive SLN. For analysis, patients were grouped according to the presence of any lobular component on surgical pathology. The number of total positive lymph nodes, cancer stage, age, final tumor size, and ER/PR/HER2 status were assessed based on tumor histology. RESULTS: We evaluated 345 previously untreated women with clinical T0-T2 and N0 disease at the time of surgery. A total of 110 patients (32%) had a component of ILC on surgical pathology. In addition, 295 patients (85.5%) had ER + breast carcinoma, 243 (70.4%) had PR + disease, 56 (16.2%) were HER2 + , and 28 (8.1%) were triple negative. At the time of surgery, women with lobular disease were observed to have a greater number of positive lymph nodes (2.79 vs 2.26; P = .009) and were more frequently upstaged to at least pathologic stage IIIA compared with nonlobular patients (30.9% vs 17.4%; P = .007). CONCLUSIONS: In this cohort, patients with a component of lobular carcinoma were more often surgically upstaged to pathologic stage IIIA or higher, which is a classical indication for postmastectomy radiation therapy. Our findings suggest that ILC is often more extensive than it appears clinically and has significant implications for management of patients with lobular carcinoma after the discovery of a positive SLN.

Stereotactic Body Radiation Therapy for Prostate Cancer: An Institutional Experience Using MRI-guided Treatment Planning.

With 222,500 new cases estimated for 2017, prostate cancer makes up approximately 10% of all new cancer diagnoses in the United States and is the third most common cancer after breast and lung cancer. In 2013, the American Society of Radiation Oncology (ASTRO) policy model recognized that stereotactic body radiation therapy (SBRT) may be used as an alternative to standard treatment modalities, i.e. intensity modulated radiation therapy (IMRT), to treat prostate cancer. In this study, we report outcomes for a cohort of 30 patients with prostate cancer treated with SBRT at our institution. We also describe, in detail, the technical aspects of SBRT planning and delivery for these patients, specifically the use of MRI in determining treatment volumes and detecting gross lesions. After institutional review board (IRB) approval, a retrospective analysis was done of 30 males with the diagnosis of prostate cancer treated in the Department of Radiation Oncology at the Baylor College of Medicine between January 2011 and June 2016. All patients received image-guided SBRT. Treatment planning was performed using a non-contrast computed tomography (CT) scan as well as a contrast thin-slice open MRI with the patient in the treatment position. Patient comparisons were done using the Mann-Whitney U, Fishers Exact, and Kaplan-Meier tests. Thirty patients were treated between January 2011 and June 2016. Twenty-six had follow-up data available and were included in the analysis. Median follow-up was 32 months (range 2-72 months). Mean and median ages at diagnosis were both 68.5 years. A total of 64% of the patients had foci on magnetic resonance imaging (MRI) or a palpable nodule on an exam. The median prostate-specific antigen (PSA) at diagnosis was 7.35 ng/mL (range 2.8-13), and the median PSA nadir after treatment was 0.4 ng/mL (range 0.01-4.5). The biochemical disease-free recurrence rate per Phoenix definition was 96%, with only one patient experiencing a biochemical recurrence four years after treatment. The patient with a recurrence was T2c, high-intermediate risk with a Gleason score of 7(3+4). He had a focus visible on MRI. Overall survival was 96%, with the only patient death unrelated to his prostate cancer. There was no statistical significance associated with recurrence and nodule on MRI (p=0.318), T-stage (p=0.222), Gleason score (p=0.890), risk group (p=0.654), age (p=0.692), or race (p=0.509). There were no grade three or four acute or long-term toxicities. SBRT of the prostate is an effective method for treating prostate cancer. We saw excellent PSA control and minimal acute or long-term toxicities after a median of three years of follow-up.

Gene set analysis of post-lactational mammary gland involution gene signatures in inflammatory and triple-negative breast cancer.

BACKGROUND: Epidemiological studies have found that triple-negative breast cancer (TNBC) and TN inflammatory breast cancer (IBC) are associated with lower frequency and duration of breast-feeding compared to non-TNBC and non-TN IBC, respectively. Limited breast-feeding could reflect abrupt or premature involution and contribute to a "primed" stroma that is permissive to the migration of cancer cells typical of IBC. We hypothesized that gene expression related to abrupt mammary gland involution after forced weaning may be enriched in the tissues of IBC patients and, if so, provide a potential correlation between limited breast-feeding and the development of aggressive breast cancer. METHODS: We utilized the Short Time-series Expression Miner (STEM) program to cluster significant signatures from two independent studies that analyzed gene expression at multiple time-points of mouse mammary gland involution. Using 10 significant signatures, we performed gene ontology analysis and gene set enrichment analysis (GSEA) on training and validation sets from human breast cancer gene expression data to identify specific genes that are enriched in IBC compared to non-IBC and in TN compared to non-TN in IBC and non-IBC groups. RESULTS: Examining the combined data, we identified 10 involution gene clusters (Inv1-10) that share time-dependent regulation after forced weaning. Inv5 was the only cluster significantly enriched in IBC in the training and validation set (nominal p-values <0.05) and only by unadjusted p-values (FDR q-values 0.26 and 0.46 respectively). Eight genes in Inv5 are upregulated in both the training and validation sets in IBC. Combining the training and validation sets, both Inv5 and Inv6 have nominal p-values <0.05 and q-values 0.39 and 0.20, respectively. The time course for both clusters includes genes that change within 12 hours after forced weaning. CONCLUSIONS: Results from this in silico study suggest correlation between molecular events during abrupt involution and aggressive breast cancer. Specifically, candidate genes from Inv5 merit functional investigation regarding the role of limited breast-feeding in IBC development.

Cochlear implantation in pediatric patients with Cockayne Syndrome.

Cockayne Syndrome (CS) is a rare, autosomal recessive disorder characterized by a spectrum of phenotypic abnormalities, including progressive sensorineural hearing loss (SNHL) that involves both peripheral and central components. To date, a single series of CS patients undergoing cochlear implant (CI) placement has been reported; this study reports on additional previously unreported pediatric CI recipients. Subjective benefits were noted early after activation in both patients, and speech perception scores improved over time as well, varying from 42 to 70% (versus 0-12% previously). Thus, we report that cochlear implantation in pediatric patients with CS can be effective in the management of progressive SNHL.

Effect of statins on breast cancer recurrence and mortality: a review.

Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are medications that have been used for decades to lower cholesterol and to prevent or treat cardiovascular diseases. Since their approval by the US Food and Drug Administration in the 1980s, other potential uses for statins have been speculated on and explored. Basic science and clinical research suggest that statins are also effective in the management of breast cancer. Specifically, in various breast cancer cell lines, statins increase apoptosis and radiosensitivity, inhibit proliferation and invasion, and decrease the metastatic dissemination of tumors. Clinical trials in breast cancer patients support these laboratory findings by demonstrating improved local control and a mortality benefit for statin users. A role for statins in the management of aggressive breast cancers with poor outcomes - namely, inflammatory breast cancer and triple-negative breast cancer - is particularly implicated. However, data exist showing that statins may actually promote invasive breast disease after long-term use and thus should be prescribed cautiously. Furthermore, a general consensus on the type of statin that should be administered, for how long, and when in relation to time of diagnosis is lacking. Given their low toxicity profile, affordability, and ease of use, consideration of statins as a therapy for breast cancer patients is imminent. In this review, we summarize current evidence regarding statins and clinical breast cancer outcomes, as well as discuss potential future studies that could shed light on this increasingly relevant topic.

Midline Craniofacial Masses in Children.

Nasal dermoids, encephaloceles, and gliomas are rare congenital lesions that result from improper embryologic development. The differentiation between them and a firm understanding of their pathology is necessary to avoid unnecessary complications. In view of their potential intracranial connection, prompt diagnosis and treatment are paramount. The authors review the embryology, diagnoses, radiologic work-up, surgical management, and complications of these midline craniofacial masses in children.

The Duplicated Thumb: A Review.

Preaxial polydactyly is a common, often sporadic, congenital anomaly that must be addressed surgically early in life. Ideally, the surgeon seeks to accomplish three goals: construction of a thumb that is adequate in size, preservation of pinch function, and reconstruction of all components in one procedure. Although each case is unique, several classification systems attempt to describe the various types. In this article, the authors discuss the various classification systems, procedures, and outcomes after surgery for pediatric thumb duplication.