The Warwick Experience of the Oncotype DX® Breast Recurrence Score® Assay as a Predictor of Chemotherapy Administration.

INTRODUCTION: Oncotype DX® analyses the expression of 21 genes within tumour tissue to determine a Recurrence Score® (RS). RS is a marker of risk for distant recurrence in oestrogen receptor-positive early breast cancer, allowing patient-specific benefit of chemotherapy to be evaluated. Our aim was to determine whether the introduction of Oncotype DX led to a net reduction in chemotherapy use. METHODS: Consecutive patients that underwent Oncotype DX at Warwick Hospital were reviewed. Patients were anonymised and re-discussed at a multidisciplinary team meeting (MDM; without RS), and treatment recommendations were recorded. This was compared to the original MDM outcome (recommendations made with RS). Differences were analysed using Wilcoxon signed-rank test. RESULTS: 67 patients were identified. Proportions of high, intermediate and low risk were 28, 33 and 39% (n = 19/22/26), respectively. Without RS, 56 (84%) patients were recommended for chemotherapy and 3 were not. The remaining 8 patients were deemed borderline for requiring chemotherapy and referred for discussion with an oncologist. With availability of RS, 34 (50%) patients were recommended for chemotherapy, and 24 (43%) patients were spared chemotherapy (p < 0.0005). The net reduction in chemotherapy was 33%. CONCLUSION: There has been a significant reduction in chemotherapy usage in patients at Warwick since the introduction of Oncotype DX.

Early multicentre experience of pre-pectoral implant based immediate breast reconstruction using Braxon®.

BACKGROUND: The last two decades have seen significant changes in surgical management of breast cancer. The offer of immediate breast reconstruction (IBR) following mastectomy is currently standard practice. Skin sparing and nipple sparing mastectomy with implant-based IBR have emerged as oncologically safe treatment options. Prepectoral implant placement and complete coverage of implant with acellular dermal matrix (ADM) eliminates the need to detach the muscle from underlying chest wall in contrast to the subpectoral technique. We report short-term outcomes of a multicentre study from the United Kingdom (UK) using Braxon® in women having an IBR. METHODS: A prospective study was conducted from December 2015 to October 2016 and included all patients from three breast units in the UK who underwent a mastectomy and an implant-based IBR using Braxon®. The demographic details, co-morbidities, operative details, immediate and delayed complications were recorded. Specific complications recorded were infection, seroma, unplanned readmission and loss of implant. A comparison was made with complications reported in the National Mastectomy and Reconstruction Audit. RESULTS: Seventy-eight IBRs were included in the analysis with a median follow-up of 9.98 months. Mean age of the cohort was 50 years with a mean body mass index of 25.7 kg/m2. Mean implant volume was 365 cc. The inpatient hospital stay was 1.48 days. About 23% of patients had a seroma, 30% had erythema requiring antibiotics and the explant rate was 10.2 percent. Bilateral reconstructions were significantly associated with implant loss and peri-operative complications on univariate analysis. CONCLUSIONS: Our early experience with this novel prepectoral technique using Braxon® has shown it to be an effective technique with complication rates comparable to subpectoral IBR. The advantages of prepectoral implant-based IBR are quicker postoperative recovery and short post-operative hospital stay. Long-term studies are required to assess rippling, post-operative animation, capsular contracture and impact of radiotherapy.

Patient anxiety on the use of one step nucleic acid amplification (OSNA) during breast cancer surgery.

INTRODUCTION: Assessment of the sentinel lymph node biopsy (SLNB) is used to stage the axilla in patients with breast cancer. There are a variety of methods to assess metastatic disease within the SLN. One-step nucleic acid amplification (OSNA) has a high sensitivity for detecting metastatic disease within the SLN and avoids the use of staged axillary surgery. However there remains a paucity of data within the literature on the psychological effects upon patients with the use of OSNA. METHODS: All patients undergoing breast surgery (breast-conserving surgery or mastectomy) and assessment of the SLNB with OSNA from December 2011 to June 2012 were included in the study. A questionnaire was sent to patient within four weeks of surgery to assess their understanding and satisfaction with the OSNA procedure. RESULTS: 60 patients responded to the questionnaire (83% response rate). All patients were female with a mean age of 63 years (range 38-71 years). 19 patients had positive SLNB as assessed by OSNA and all had ALND. 15 patients expressed pre-operative anxiety about having OSNA although 97% stated that they would be happy to undergo the same procedure again. CONCLUSION: Our study has identified the anxiety points that patients experience with OSNA based management and this will allow improved direct emotional support and provision of information.

Patients' perspective on day case breast surgery.

BACKGROUND: This study assessed the views of patients undergoing breast surgery for breast cancer with a planned overnight stay, asking whether they would be happy to be discharged home on the same day of surgery. METHODS: A structured questionnaire sent out in the 6 weeks following surgery was used to ascertain the patients' views. RESULTS: The majority of patients undergoing mastectomy and axillary node clearance preferred an overnight stay, primarily for psychological reasons. CONCLUSIONS: Patients undergoing breast-conserving surgery were more prepared to go home on the day of surgery.

Comprehensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer: increased expression of matrix metalloproteinase-7 predicts poor survival.

PURPOSE: To enable the design of improved inhibitors of matrix metalloproteinases (MMPs) for the treatment of pancreatic cancer, the expression profiles of a range of MMPs and tissue inhibitors of MMPs (TIMPs) were determined. EXPERIMENTAL DESIGN: Nine MMPs (MMPs 1-3, 7-9, 11, 12, and 14) and three TIMPs (TIMPs 1-3) were examined in up to 75 pancreatic ductal adenocarcinomas and 10 normal pancreata by immunohistochemistry. Eighteen additional pancreatic ductal adenocarcinomas and an additional eight normal pancreata were also analyzed by real-time reverse transcription-PCR and additionally for MMP-15. RESULTS: There was increased expression by immunohistochemistry for MMPs 7, 8, 9, and 11 and TIMP-3 in pancreatic cancer compared with normal pancreas (P < 0.0001, 0.04, 0.0009, 0.005, and 0.0001, respectively). Real-time reverse transcription-PCR showed a significant increase in mRNA levels for MMP-11 in tumor tissue compared with normal pancreatic tissue (P = 0.0005) and also significantly reduced levels of MMP-15 (P = 0.0026). Univariate analysis revealed that survival was reduced by lymph node involvement (P = 0.0007) and increased expression of MMP-7 (P = 0.005) and (for the first time) MMP-11 (P = 0.02) but not reduced by tumor grade, tumor diameter, positive resection margins, adjuvant treatment, or expression of the remaining MMPs and TIMPs. On multivariate analysis, only MMP-7 predicted shortened survival (P < 0.05); however, increased MMP-11 expression was strongly associated with lymph node involvement (P = 0.0073). CONCLUSIONS: We propose that the principle specificity for effective inhibitors of MMPs in pancreatic cancer should be for MMP-7 with secondary specificity against MMP-11. Moreover, these studies indicate that MMP-7 expression is a powerful independent prognostic indicator and potentially of considerable clinical value.

CT and pathologic assessment of prospective nodal staging in patients with ductal adenocarcinoma of the head of the pancreas.

OBJECTIVE: The aim of our study was to compare the assessment of peripancreatic lymph nodes using CT with the gold standard of detailed histopathologic assessment of resected specimens in patients with pancreatic ductal adenocarcinoma. SUBJECTS AND METHODS: Sixty-two patients with presumed pancreatic carcinoma were prospectively studied with dual-phase contrast-enhanced helical CT, and images were interpreted in consensus by three radiologists. Complete surgical resection was performed in 28 patients. A detailed nodal classification system was used for radiologic, surgical, and pathologic staging in the nine patients whose final diagnosis at histology was pancreatic ductal adenocarcinoma. RESULTS: Forty lymph nodes were prospectively identified on CT in these nine patients. Two of 23 nodes (9%) measuring less than 5 mm in the short-axis diameter were malignant, four of 11 nodes (36%) measuring 5-10 mm were malignant, and one of six nodes (17%) larger than 10 mm was malignant. Using a short-axis diameter of greater than 10 mm as the criterion for nodal involvement, we found a sensitivity of 14% (1/7) and a specificity of 85% (28/33), with a positive predictive value of 17% (1/6), a negative predictive value of 82% (28/34), and an overall accuracy of 73% (29/40). Ovoid nodal shape, clustering of nodes, and the absence of a fatty hilum were not useful predictors of malignancy on CT. CONCLUSION: In resectable pancreatic ductal adenocarcinoma, CT is not accurate overall for the prediction of nodal involvement. In a patient with presumed pancreatic carcinoma that is considered to be resectable, the depiction on CT of peripancreatic nodes should not prevent attempted curative resection.