Correlation Between Oncotype DX, PREDICT and the Nottingham Prognostic Index: Implications for the Management of Early Breast Cancer.

Introduction Breast cancer remains the most common cancer diagnosis in the UK. The current clinical practice utilises two different types of modalities to estimate the prognosis, risk of recurrence and benefit from adjuvant chemotherapy treatment in patients with early breast cancer. The first set of modalities includes risk calculators based on clinicopathological features, e.g. PREDICT or the Nottingham Prognostic Index (NPI); the second includes genetic profiling of tumour tissue using Oncotype DX (ODX; Genomic Health, Redwood City, CA) testing. PREDICT, NPI and ODX stratify breast cancers into high-, intermediate- and low-risk categories to help guide adjuvant chemotherapy treatment decisions. This study compares PREDICT, NPI and ODX Recurrence Scores (RS), with the aim of assessing 1) the correlation between the RS for PREDICT, NPI and ODX and 2) whether early breast cancer patients are stratified into similar risk categories by all three modalities. Methods This retrospective study included early breast cancer patients treated at a National Health Service (NHS) hospital over a 12-month period (October 1, 2017 to September 30, 2018). Inclusion criteria: consecutive patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node-negative breast cancer. All patients were discussed at the local multidisciplinary team (MDT) meeting and underwent ODX testing. Exclusion criteria: patients without ODX test scores; patients with an in-breast recurrence; patients who did not undergo a sentinel lymph node biopsy (SLNB); and patients with ductal carcinoma in situ (DCIS) only. NPI and PREDICT scores were calculated for each patient using online tools, and ODX data was obtained through Genomic Health and MDT records. Patients were risk-stratified into high, intermediate and low risk of recurrence groups based on their PREDICT, NPI and ODX scores. The thresholds for risk stratification were based on current practice, which is evidence-based. Correlations between PREDICT, NPI and ODX scores were analysed using Spearman's correlation coefficient. Results Forty-six patients (mean age: 56 years), with a total of 57 early breast cancers, underwent ODX testing. Risk categories generated by PREDICT very strongly correlated with NPI for all patients (r=0.92; P<0.0001). However, the RS generated by ODX testing only strongly correlated for patients with low-risk PREDICT scores (r=0.51; P=0.0134), while no correlation between RS and PREDICT was observed for patients with intermediate- or high-risk PREDICT scores (r=-0.0064; P=0.9767). Similar results were seen between NPI and RS. Overall, only 19/46 (41.3%) patients had an RS which corresponded to PREDICT risk category, while 18/46 (39.1%) patients had an RS that indicated a higher risk of recurrence than PREDICT, and 9/46 (19.6%) patients had an RS indicating a lower risk of recurrence than PREDICT. Similar results were found when comparing RS and NPI. Conclusion The risk of recurrence estimated by ODX in patients deemed low risk by PREDICT or NPI highly correlated, while no such correlation existed in patients with an estimated intermediate- or high-risk breast cancer. In PREDICT- or NPI-estimated intermediate- and high-risk patients, ODX provided valuable additional prognostic information to guide adjuvant treatment, while the potential avoidance of ODX testing in low-risk patients presents significant cost-savings.

The Utility of Oncotype DX for Adjuvant Chemotherapy Treatment Decisions in Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative, Node-negative Breast Cancer.

Introduction Breast cancer is the most common cancer diagnosis in the UK. Recently, there has been a reduction in breast cancer-specific mortality and recurrence attributed, in part, to the delivery of adjuvant chemotherapy. The National Institute for Health and Care Excellence (NICE) recommends the use of genetic profiling with Oncotype DX (ODX) to guide decisions to offer adjuvant chemotherapy after surgery in intermediate-risk early breast cancer patients. This study aimed to evaluate the utility of ODX testing in routine clinical practice in a National Health Service (NHS) hospital.  Methods Consecutive early breast cancer patients, identified through the multidisciplinary team (MDT) records, treated in our institution over 12 months (October 2017-September 2018) were included. PREDICT and Nottingham prognostic index (NPI) scores (from online clinicopathological recurrence risk tools) were calculated for each patient, and ODX data obtained through Genomic Health, Inc. (Redwood City, California). Patients were divided into two groups, those that underwent ODX testing (ODX group) and those that did not (non-ODX group). Descriptive statistics were used to analyse patient and tumour characteristics. The Gaussian distribution of each data set was assessed using the Anderson-Darling test. For comparisons between patient groups, the non-parametric equivalent of the two-tailed t-test (Mann-Whitney) was used. Dichotomous variables (e.g. chemotherapy decisions) were compared using chi-squared tests. Results One-hundred thirty-three patients (mean age 62 years) treated for 152 early breast cancers, were included in the final analysis. Breast cancers in the ODX group were of greater median tumour size (24 vs 16 mm; P<0.0001) and higher median tumour grade (3 vs 2; P<0.0001). PREDICT scores (3 vs 1, P<0.0001) and NPI scores (3.40 vs 2.30, P<0.0001) for the ODX group were also significantly higher than the non-ODX group. A greater proportion of patients were offered chemotherapy in the ODX group (39.9% vs 6.9%, P<0.001). However, for the PREDICT-calculated intermediate-risk patients, ODX testing resulted in a lower proportion of patients being offered chemotherapy compared to the intermediate-risk patients who were not genetically profiled (54.5% vs 83.3%, P=0.3547), although this result was not statistically significant. Conclusions Patients selected for ODX testing were younger, with significantly higher-grade and larger-sized tumours compared to patients not selected for genetic profiling. ODX testing significantly impacted the delivery of chemotherapy, as the recurrence score generated through ODX testing guided the final decision.

Safety of radioactive sentinel node biopsy for breast cancer and the pregnant surgeon - A review.

INTRODUCTION: Sentinel node biopsy is an established key element in the surgical management of breast cancer and melanoma. Several studies have assessed radiation exposure during sentinel node biopsy and confirmed it to be safe for health workers. Recent demographic changes amongst surgeons has resulted in increasing numbers of women of childbearing age performing sentinel node procedures as a regular part of their surgical practice. We aimed to assess the radiation risk posed by sentinel node biopsy in breast cancer surgery to pregnant surgeons. METHODS: A search of indexed citations from PUBMED and Cochrane databases for studies assessing the radiation exposure to the primary surgeon during sentinel node biopsy was undertaken. Due to the variability of melanoma location in relation to nodal basins, we have focused on sentinel node biopsy for breast cancer where surgeon positioning, radiopharmaceutical injection and nodal dissection sites are consistent. RESULTS: From the eleven studies totalling 344 procedures, exposure doses to the abdomens and fingers of surgeons undertaking sentinel node biopsy were within the guideline maximum recommended exposure limit of 1 mSv as set out by the International Committee on Radiation Protection (ICRP) 107 recommendations as long as fewer than one hundred procedures are performed throughout the duration of the pregnancy. Of note the radiation doses in the newer studies were much lower and used more sensitive instruments to detect radiation exposure. CONCLUSIONS: Providing the numbers of procedures are within defined limits, the radiation risks posed to pregnant surgeons undertaking sentinel node procedures are limited and within the regulatory guidelines for pregnancy.

An 81 Year Old with Back Pain.

You see an 81-year-old man in the emergency department. He has been troubled by abdominal and back pain that has been worsening over the last two days. He has smoked 20 cigarettes a day for the last 60 years. On examination his heart rate is 110 beats per minute and his blood pressure is 130/80 mmhg. He is tender over the central abdomen and you feel a pulsatile mass above the umbilicus. You request a CT scan of the abdomen.

68-Year-Old Man with PR Bleed.

A 68-year-old man is referred to the colorectal clinic by his GP. He has lost 10 kg in weight over the last two months. He also noticed that his bowel motions have been loose and sometimes contain blood. You review the full blood count and faecal occult blood test the GP requested. What should you do next?

Postpartum pneumoperitoneum: an important clinical lesson.

A 23-year-old primigravida presented to accident and emergency department with a 4-day history of generalised abdominal pain associated with vomiting and diarrhoea. She had previously given birth to her first child by vaginal delivery 6 days previously at another hospital and suffered a third-degree vaginal tear following prolonged labour. Shortly after birth, the patient had described the unusual symptom of soft tissue crepitations in the neck, but had been reassured and discharged without further investigation by her obstetrics team and reassured by a visiting general practitioner. At representation, the patient had obvious pneumoperitoneum, which was missed by the admitting team and underwent laparotomy for perforated duodenal ulcer.

Strategies for localisation of impalpable breast lesions.

With advances in the sensitivity of mammographic screening and the broader population of women screened via national programmes. More than 50% of all new breast cancers in the United Kingdom are screen-detected and of the 11,110 invasive breast cancers (78.7 per cent of all UK cancers) detected in the year 2007-2008, 5814 (52.3 per cent) measured 15 mm or less in diameter and were deemed clinically non-palpable. For excision of non-palpable lesions, localisation techniques are currently largely limited to wire-guided localisation with the associated risks of migration, transection and scheduling conflicts. In this review we will describe the current gold-standard of wire-guided localisation (WGL), its associated merits and limitations before reporting on the data available for Radioguided Occult Lesion Localisation (ROLL) and Radiolabeled Seed Localisation (RSL) trials.

Faecal peritonitis secondary to perforated recto sigmoid colon by a large gallstone: a case report.

Large bowel obstruction is an important surgical emergency. The cause of obstruction may be benign or malignant, and include large bowel volvulus, polyps, intraperitoneal adhesions, strictures and neoplastic growths. Large bowel obstruction caused by gallstone(s) is a very rare phenomenon and not many cases are reported in the English literature. The present report describes a case of large bowel obstruction and faecal peritonitis caused by a gallstone perforating sigmoid colon. A database search (PubMed) did not locate any cases of large bowel perforation by a gallstone in the English literature, and hence this case report may be the first on this subject.

Postpartum pneumoperitoneum and peritonitis after water birth.

Pneumoperitoneum (the presence of free gas in the peritoneal cavity) usually indicates gastrointestinal perforation with associated peritoneal contamination. We describe the unusual case of a 28-year-old female, who was 7 days postpartum and presented with features of peritonitis that were initially missed despite supporting radiological evidence. The causes of pneumoperitoneum are discussed. In the postpartum period the female genital tract provides an alternative route by which gas can enter the abdominal cavity and cause pneumoperitoneum. In the postpartum period it is important to remember that the clinical signs of peritonism, guarding and rebound tenderness may be diminished or subtle due to abdominal wall laxity.

Henoch-Schonlein purpura with ischaemic bowel.

Henoch-Schonlein purpura is a vasculitis affecting small arterial vessels. Occasionally, cases are referred for a general surgical opinion due to bowel involvement in the form of abdominal pain with or without rectal bleeding. However, surgical intervention is rarely required. We describe a case of Henoch-Schonlein purpura in a young man who went on to develop ischaemic bowel requiring resection.