Breast Cancer Molecular Subtyping in Practice: A Real-World Study of the APIS Breast Cancer Subtyping Assay in a Consecutive Series of Breast Core Biopsies.

The APIS Breast Cancer Subtyping Kit is an mRNA-based assessment of the seven parameters including three biomarkers routinely assessed in all the newly diagnosed breast cancers (BC), oestrogen receptor (ER), progesterone receptor (PR) and HER-2 and an additional four genes that create a novel proliferation signature, MKI67, PCNA, CCNA2 and KIF23. Taken together, the data are used to produce a molecular subtype for every sample. The kit was evaluated against the current standard protocol of immunohistochemistry (IHC) and/or in situ hybridisation (ISH) in breast cancer patients. The data were presented at the weekly breast multidisciplinary team (MDT) meeting. A total of 98 consecutive cases of pre-operative breast cancer core biopsies and two core biopsies of nodal metastases yielding 100 cases were assessed. IHC and APIS results were available for 100 and 99 cases. ER was concordant in 97% cases, PR was concordant in 89% and HER-2 results were concordant with IHC/ISH in 100% of the cases. Ki-67 IHC was discordant in 3% of cases when compared with MK167 alone but discordant in 24% when compared with the four-gene proliferation signature. In conclusion, our study indicates that the APIS Breast Cancer Subtyping Kit is highly concordant when compared to the results produced for ER/PR/HER-2 by IHC and/or ISH. The assay could play a role in the routine assessment of newly diagnosed breast cancer (BC) specimens.

Breast cancer metastasis burden in sentinel nodes analysed using one-step nucleic acid amplification predicts axillary nodal status.

BACKGROUND: In breast cancer patients undergoing sentinel lymph node biopsy (SLNB) analysis using one-step nucleic acid amplification (OSNA), clarity is required as to the risk factors for non-sentinel lymph node (NSLN) involvement upon axillary lymph node dissection (ALND). This study aims to identify these factors, including categorising by extent of sentinel node positivity: solitary positive node (solitary), multiple nodes with some positive (multiple incomplete positive), or multiple nodes all of which are positive (multiple all positive). METHODS: We conducted a cohort study using prospectively collected data on 856 SLNBs analysed using OSNA, from patients with cT1-3 clinically node-negative invasive breast cancer. ALND was performed for 289 positive SLNBs. RESULTS: NSLN metastases were identified in 73 (25.3%) ALNDs. Significant factors for NSLN involvement on multivariate analysis were: SLNB macrometastases (cytokeratin-19 mRNA count >5000 copies/µl) (adj.OR = 3.01; 95% CI, 1.61-5.66; p = 0.0006), multiple all positive vs. multiple incomplete positive SLNB (adj.OR = 2.92; 95% CI, 1.38-6.19; p = 0.0050), and undergoing mastectomy (adj.OR = 1.89; 95% CI, 1.00-3.55; p = 0.0486). Amongst multiple incomplete positive SLNBs, an 8.8% NSLN risk was identified when only micrometastases were present. CONCLUSION: Extent of sentinel lymph node positivity measured using OSNA predicts NSLN metastasis risk, aiding decisions surrounding axillary treatment.

Diagnosis and management of retroareolar cysts in adolescents: a case report.

Retroareolar cysts are a rare condition of the adolescent female breast and their reported incidence in the literature is scarce. Arising from obstruction of the terminal channels that drain Montgomery's areolar tubercles retroareolar cysts comprise two different pathological entities; symptomatic and asymptomatic. We report on a case of a symptomatic retroareolar cyst in a 15-year-old girl and review the literature. We highlight the subtle clinical differences from other adolescent breast masses, describe the natural course of the condition and with respect to diagnosis detail the correlation between clinical features and characteristic sonographic findings. Finally, we highlight the importance of preserving the developing breast bud by adopting a conservative approach to the management of retroareolar cysts.

Traction removal of percutaneous endoscopic gastrostomy devices in children.

BACKGROUND: There are few published data on non-endoscopic removal of percutaneous endoscopic gastrostomy devices in children. AIMS: To describe prospective data acquired for traction removal of percutaneous endoscopic gastrostomy devices at a single pediatric center over a 5-year period. METHODS: Data were obtained from endoscopy records, computerized hospital patient information systems and case note analysis. The device that could be removed by traction was the Corflo (Merck) 12-Fr percutaneous endoscopic gastrostomy tube with a collapsible internal retention dome. All procedures were performed under general anesthesia. RESULTS: Between 2002-2006, 220 children underwent percutaneous endoscopic gastrostomy removals (166 by traction, 51 endoscopically and 3 Foley catheter to button conversions). The median duration between percutaneous endoscopic gastrostomy insertion and low profile button device substitution was 0.83 years (0.12-3.86). Complications from traction removal included internal retention dome separation in two cases (allowed to pass per rectum, uneventfully), failure to a insert a low profile button device needing percutaneous endoscopic gastrostomy reinsertion, enterocutaneous fistula requiring surgical closure in one patient and laparoscopy for suspected low profile button device misplacement in one instance. The material cost of endoscope disinfection (£10) and disposable usage (£80) avoided by traction removal was calculated at £90 per procedure. CONCLUSION: No mortality occurred as a result of the traction removal of percutaneous endoscopic gastrostomy tubes. Laparoscopy for suspected low profile button device misplacement was needed in one case (0.60%). Traction removal of percutaneous endoscopic gastrostomy tubes was generally safe and a cost-saving procedure in our experience.

Indications for percutaneous endoscopic gastrostomy and procedure-related outcome.

OBJECTIVE: : To describe the indications and practice of percutaneous endoscopic gastrostomy (PEG) device insertion for nutritional support and to ascertain procedure-related complications and outcome. METHODS: : Observational study with prospectively collected data on children who underwent PEG-related procedures (PEG insertion, removal, or change to low profile button devices [LPBD]) for a 5-year period (2002-2006) at our centre. RESULTS: : Six hundred one PEG-related procedures were performed during the study period (384 insertions, 165 conversions to LPBD, 49 permanent PEG removals, and 3 PEG reinsertions). The main indications for PEG insertion were feeding difficulties associated with neurodisability (160/384; 41.6%) and congenital heart disease (CHD 115/384; 30%). Children with CHD required feeding nutritional support at an earlier age than children with neurodisability regardless of underlying cardiac condition. The age of PEG insertion was significantly different between the 2 main groups (neurodisability 3.56 years vs CHD 0.39 years; P < 0.001 [t test]). Fifty-nine patients were discharged on the same day as PEG insertion without complications (day case gastrostomy). The median time between PEG insertion to LPBD conversion was 0.83 year (0.12-3.86). Twenty-four of the 49 children having permanent PEG removal had CHD. CONCLUSIONS: : Neurodisabilty and CHD were the main indications for PEG insertion, those with CHD requiring feeding support at an earlier age. Although CHD was an indication for PEG insertion in 30% of instances, a greater percentage of PEG removals (50%) were seen in this group indicating resolution of feeding difficulties.

Biology and treatment of ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is responsible for 25% of screen-detected breast cancers. Various prognostic classifications are in use, including the Van Nuys Prognostic Index and the European Organisation for Research and Treatment of Cancer grading system (well, intermediate or poorly differentiated) based on cytonuclear pattern. This has been modified in screening programs to low, intermediate and high grade. In comparison with normal epithelium, DCIS has a tenfold increase in growth and 15-fold increase in apoptosis. Patients with extensive or multifocal DCIS need mastectomy and sentinel node biopsy, together with reconstruction, if requested. Microinvasion associated with DCIS is an indication for sentinel node biopsy. Randomized trials have confirmed the value of breast irradiation after wide excision, in terms of DCIS relapse and progression to invasive disease. Patients with estrogen receptor-positive DCIS benefit from adjuvant tamoxifen after breast-conserving surgery.