Evaluating the Necessity for Routine Sentinel Lymph Node Biopsy in Postmenopausal Patients Being Treated for Clinically Node Negative Breast Cancer the Era of RxPONDER.

INTRODUCTION: Traditionally, sentinel lymph node biopsy (SLNB) was performed to inform adjuvant chemotherapy prescription and prognosis in breast cancer. Following RxPONDER, the OncotypeDX Recurrence Score (RS) guides adjuvant chemotherapy prescription for all postmenopausal patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative (ER+/HER2-) breast cancer with 0 to 3 positive lymph nodes (0-3 + LN). AIMS: To establish the oncological safety of omitting SLNB in postmenopausal patients with ER+/HER2- breast cancer indicated to undergo SLNB and to evaluate the primary determinants of chemotherapy prescription for these patients. PATIENTS AND METHODS: A retrospective cohort study was undertaken. Cox regression and Kaplan-Meier analyses were performed. Data analytics was performed using SPSS v26.0. RESULTS: Five hundred and seventy five consecutive patients were included (mean age: 66.5 years, range: 45-96). The median follow-up was 97.2 months (range: 3.0-181.6). Of the 575 patients, just 12 patients had positive SLNB (SLNB+) (2.1%). Using Kaplan-Meier analyses, SLNB+ failed to impact recurrence (P = .766) or mortality (P = .310). However, using Cox regression analyses, SLNB+ independently predicted poorer disease-free survival (hazard ratio: 1.001, 95% confidence interval (95% CI): 1.000-1.001, P = .029). Logistic regression analysis identified RS as the sole predictor of chemotherapy prescription (odds ratio: 1.171, 95% CI: 1.097-1.250, P < .001). CONCLUSION: Omitting SLNB may be safe and justifiable in postmenopausal patients with ER+/HER2- breast cancer with clinically negative axillae. Following RxPONDER, RS is the most important guide of chemotherapy use in these patients and SLNB may be less important than previously perceived. Prospective, randomized clinical trials are required to fully establish the oncological safety of omitting SLNB in this setting.

A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

Comparison of the Nottingham Prognostic Index and OncotypeDX© recurrence score in predicting outcome in estrogen receptor positive breast cancer.

INTRODUCTION: Traditionally, Nottingham prognostic index (NPI) informed prognosis in patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, node negative (ER+/HER2-/LN-) breast cancer. At present, OncotypeDX© Recurrence Score (RS) predicts prognosis and response to adjuvant chemotherapy (AC). AIMS: To compare NPI and RS for estimating prognosis in ER + breast cancer. METHODS: Consecutive patients with ER+/HER2-/LN- disease were included. Disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier and Cox regression analyses. RESULTS: 1471 patients met inclusion criteria. The mean follow-up was 110.7months. NPI was calculable for 1382 patients: 19.8% had NPI≤2.4 (291/1471), 33.0% had NPI 2.41-3.4 (486/1471), 30.0% had NPI 3.41-4.4 (441/1471), 10.9% had NPI 4.41-5.4 (160/1471), and 0.3% had NPI>5.4 (4/1471). In total, 329 patients underwent RS (mean RS: 18.7) and 82.1% had RS < 25 (270/329) and 17.9% had RS ≥ 25 (59/329). Using multivariable Cox regression analyses (n = 1382), NPI independently predicted DFS (Hazard ratio (HR): 1.357, 95% confidence interval (CI): 1.140-1.616, P < 0.001) and OS (HR: 1.003, 95% CI: 1.001-1.006, P = 0.024). When performing a focused analysis of those who underwent both NPI and RS (n = 329), neither biomarker predicted DFS or OS. Using Kaplan Meier analyses, NPI category predicted DFS (P = 0.008) and (P = 0.026) OS. Conversely, 21-gene RS group failed to predict DFS (P = 0.187) and OS (P = 0.296). CONCLUSION: In our focused analysis, neither NPI nor RS predicted survival outcomes. However, in the entire series, NPI independently predicted both DFS and OS. On the 40th anniversary since its derivation, NPI continues to provide accurate prognostication in breast cancer, outperforming RS in the current study.

A Novel Surrogate Nomogram Capable of Predicting OncotypeDX Recurrence Score©.

Background: OncotypeDX Recurrence Score© (RS) is a commercially available 21-gene expression assay which estimates prognosis and guides chemoendocrine prescription in early-stage estrogen-receptor positive, human epidermal growth factor receptor-2-negative (ER+/HER2−) breast cancer. Limitations of RS testing include the cost and turnaround time of several weeks. Aim: Our aim is to develop a user-friendly surrogate nomogram capable of predicting RS. Methods: Multivariable linear regression analyses were performed to determine predictors of RS and RS > 25. Receiver operating characteristic analysis produced an area under the curve (AUC) for each model, with training and test sets were composed of 70.3% (n = 315) and 29.7% (n = 133). A dynamic, user-friendly nomogram was built to predict RS using R (version 4.0.3). Results: 448 consecutive patients who underwent RS testing were included (median age: 58 years). Using multivariable regression analyses, postmenopausal status (ß-Coefficient: 0.25, 95% confidence intervals (CIs): 0.03−0.48, p = 0.028), grade 3 disease (ß-Coefficient: 0.28, 95% CIs: 0.03−0.52, p = 0.026), and estrogen receptor (ER) score (ß-Coefficient: −0.14, 95% CIs: −0.22−−0.06, p = 0.001) all independently predicted RS, with AUC of 0.719. Using multivariable regression analyses, grade 3 disease (odds ratio (OR): 5.67, 95% CIs: 1.32−40.00, p = 0.037), decreased ER score (OR: 1.33, 95% CIs: 1.02−1.66, p = 0.050) and decreased progesterone receptor score (OR: 1.16, 95% CIs: 1.06−1.25, p = 0.002) all independently predicted RS > 25, with AUC of 0.740 for the static and dynamic online nomogram model. Conclusions: This study designed and validated an online user-friendly nomogram from routinely available clinicopathological parameters capable of predicting outcomes of the 21-gene RS expression assay.

Breast cancer recurrence: factors impacting occurrence and survival.

BACKGROUND: Breast cancer mortality has decreased due to improved screening and treatment options. Nevertheless, 25-30% of patients develop disease recurrence and die from the disease dissemination. Patients who develop metastatic disease represent a heterogeneous group and management plans are dependent on molecular subtype, disease burden and metastatic site. AIM: To determine predictive clinicopathological factors of disease recurrence and their impact on survival in the molecular era. METHODS: Consecutive patients who breast cancer developed recurrence at our tertiary referral centre between 2000 and 2015 were included. Clinicopathological and treatment data were assessed using descriptive statistics. Oncological outcome was assessed using Cox regression and Kaplan Meier analyses. RESULTS: Two hundred sixty-five consecutive patients who developed breast cancer recurrence were included; median age at metastasis was 59.3 years (range 27-87 years), and median time to recurrence (TTR) was 47.7 ± 38.5 months (range 3.0-194.3 months). Survival was 24.2% (64/265) 53.2% were luminal A (LABC) (141/265), 18.5% were luminal B (LBBC) (49/265), 18.5% were triple negative (TNBC) (49/265), and 9.8% were human epidermal growth factor receptor-2 overexpressing (HER2 +) (26/265). TTR for patients with LABC was 56.0 ± 41.3 months, LBBC was 48.4 ± 41.1 months, TNBC was 26.9 ± 28.5 months and HER2 + was 34.3 ± 21.8 months. Increased grade (P < 0.001), Nottingham Prognostic Indices (P < 0.001), TNBC (P < 0.001), HER2 + subtype (P < 0.001) and receiving targeted therapy (P = 0.006) predicted shorted TTR. Estrogen receptor positivity (P < 0.001), progesterone receptor positivity (P = 0.010), invasive lobular carcinoma (P = 0.009) and receiving endocrine therapy (P = 0.001) predicted longer TTR. CONCLUSION: Readily available clinicopathological factors predict risk of metastatic dissemination. Developing a tailored program to identify patients at risk of recurrence is crucial in controlling metastatic dissemination of breast cancer.

Schwannoma of the Appendix Orifice.

Schwannomas are rare mesenchymal tumors. They are usually diagnosed incidentally during endoscopic or diagnostic imaging for another reason. Malignant transformation is rare. In this case report, we present an incidental schwannoma protruding through the appendiceal orifice diagnosed during endoscopy. A healthy 56-year-old female underwent a surveillance colonoscopy for family history of colorectal cancer. A prominent and edematous appendiceal orifice was noted, and the area was aggressively biopsied. Histopathological assessment revealed a benign schwannoma. Computerized topography was unremarkable. Subsequently, the patient underwent a right hemicolectomy. Patient is scheduled to undergo routine surveillance in three years. Grossly, schwannomas are white, encapsulated, and well-circumscribed lesions that stain strongly positive for S100, GFAP, and CD57. Histologically, schwannomas demonstrate spindle cell proliferation. Several imaging modalities have been utilized in the diagnosis and management of mesenchymal neoplasms. Despite the benign nature of the diagnosis, complete surgical resection with clear margins remains the gold standard management strategy. Our case highlights the presence of a relatively uncommon tumor in an unusual anatomical location.

Clinicopathological response to neoadjuvant therapies and pathological complete response as a biomarker of survival in human epidermal growth factor receptor-2 enriched breast cancer - A retrospective cohort study.

BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is overexpressed in 20-25% of breast cancers. Complete eradication of disease following neoadjuvant therapies and chemotherapy has been referred to as pathological complete response (pCR). AIMS: To determine clinicopathological predictors of pCR to neoadjuvant therapies and to evaluate pCR as a surrogate to enhanced survival. METHODS: Consecutive female patients with HER2 positive (HER+) breast cancer managed surgically in a single institution between 2005 and 2015 were included. Descriptive statistics and binary logistic regression were used to determine predictors of pCR. Appraisal of pCR as a predictor of survival was performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: 451 patients were included with a mean age of 56.6 ± 13.4 years (range 23-95). Disease-free (DFS) and overall survival (OS) was 82.3% (371/451) and 82.6% (376/451) respectively with a median follow-up of 108.0 months (range 3-184.0). 118 were treated in the neoadjuvant setting (26.2%): tumour size <50 mm (Odds Ratio (OR): 12.156, P = 0.023) and progesterone receptor negativity (OR: 2.762, P = 0.008) independently predicted breast pCR, while ductal carcinoma (OR: 3.203, P = 0.030) and grade 3 disease (OR: 2.788, P = 0.018) predicted axillary pCR. Both breast and axillary pCR predicted enhanced DFS (Hazard Ratio (HR): 0.470 & HR: 0.449) and OS (HR: 0.383 & HR: 0.307). Axillary pCR independently predicted improved OS (HR: 0.326). CONCLUSION: pCR is sensitive biomarker and surrogate to survival outcomes in HER2+ breast cancer. Patients likely to achieve pCR may be predicted from traditional clinicopathological characteristics and molecular parameters.

Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre.

Oncotype DX™ (ODX) score estimates prognosis and predicts breast cancer recurrence. It also individualizes patient adjuvant chemotherapy prescription in breast cancer. This assay relies on genetic and molecular markers; the clinicopathological phenotype of which are tested routinely. The aim of this study was determine whether clinicopathological and immunohistochemical information predicts ODX recurrence score (RS). Secondly, to assess the impact on adjuvant chemotherapy (AC) and oncological outcome of ODX testing in patients in a European tertiary referral center. Estrogen receptor positive (ER+), human epidermal growth factor receptor-2 negative (HER2-), lymph node negative (LN-), and female breast cancer patients with ODX testing performed between 2007 and 2015 were categorized into low- (<11), intermediate- (11-25), and high-risk (>25) groups. Clinicopathological and immunohistochemical correlates of RS were determined. Predictors of RS were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analyses. ODX was performed in 400 consecutive ER+LN- patients. Median follow-up was 74.1 months (3.0-144.4). Low grade (odds ratio [OR]:2.39; 95% confidence interval [CI]:1.04-5.51, p = 0.041) independently predicted low ODX, while high grade (OR:2.04; 95% CI: 1.19-3.49, p = 0.009) and reduced progesterone receptor (PgR) expression (OR: 2.57, 95% CI: 1.42-4.65, p = 0.002) independently predicted high ODX. Omission of AC in intermediate- (p = 0.159) and high-risk (p = 0.702) groups did not negatively impact survival. In conclusion, tumor grade independently predicts low and high RS, while PgR negativity predicts high RS. ODX reduced AC prescription without compromising oncological outcome.

Neoadjuvant chemotherapy for luminal a breast cancer: Factors predictive of histopathologic response and oncologic outcome.

BACKGROUND: The benefit of chemotherapy (NAC) for patients with ER/PR positive, HER2 negative breast cancer is unclear. Our aim was to determine factors associated with histopathologic response and oncologic outcome following NAC in this group. METHODS: Consecutive female patients undergoing neoadjuvant therapy and surgery for locally advanced Luminal A breast cancer between 2010 and 2015 were studied. Multivariable linear, logistic, and Cox regression analysis was undertaken. RESULTS: 114 patients were studied. Pathological complete response (pCR) was achieved in 7.9% of patients, ypN0 in 25.5%, and downstaging in 33.6%. However, 43.9% exhibited a Sataloff C-D response. Tumor grade independently predicted pCR (P = 0.039), while PR score predicted ypN0 (P = 0.017) and downstaging (P=0.029). 5-year invasive disease-free (iDFS) and overall survival (OS) were 68.5 ± 4.7% and 77.7 ± 4.3%, respectively. CONCLUSION: After NAC for Luminal A breast cancer, pCR rates are low. Patients with high grade tumors with weak PR expression exhibit the most promising response rates.

A prospective feasibility study of MammoSite accelerated partial breast irradiation for early breast Cancer.

BACKGROUND: Accelerated partial breast irradiation is a potential alternative to standard whole breast irradiation, following breast-conserving surgery, in the management of breast cancer. The MammoSite applicator-based technique allows for the delivery of a higher dose of radiation to the tumour bed and adjacent area, over a shorter treatment period. AIMS: To investigate the long-term feasibility of the MammoSite technique in early stage breast cancer in an Irish cohort. METHODS: Sixty-two patients with early stage breast cancer were enrolled in this prospective study between November 2005 and October 2012 at the University Hospital Galway. A single-entry MammoSite applicator was inserted post-operatively. A CT scan was performed to assess the balloon to skin distance, the conformance of target tissue to balloon surface and balloon symmetry. A total dose of 34 Gy was delivered over 10 fractions twice daily. RESULTS: Median follow-up was 10 years. 91.9% (57/62) completed the full course of MammoSite treatment. Technical issues with the MammoSite balloon precluded three patients from completing the full course of treatment. On last follow-up, 6.4% (4/62) of patients had developed an ipsilateral breast recurrence. Half of these recurrences occurred more than 10 years after the initial breast cancer treatment. The most common toxicities observed were fibrosis (67.7%), pain (61.3%) and skin erythema (35.5%). CONCLUSION: The use of the MammoSite technique, as an alternative to standard whole breast irradiation, is feasible in a typical Irish clinical setting with integrated multidisciplinary team input.

Multidisciplinary approach to chest wall reconstruction in primary breast angiosarcoma resection.

Angiosarcomas account for less than 1% of primary breast cancers. Typically, they occur in young women with a low-risk personal or family history. Diagnosis, resection and reconstruction require a multidisciplinary team of breast surgeons, oncologists and plastic reconstructive surgeons. Cross-disciplinary awareness among these specialities enables dimensional patient treatment. We report a case of primary angiosarcoma of the breast in a 33-year-old woman, with no previous radiotherapy exposure, treated with a radical mastectomy and chest wall reconstruction with a deep inferior epigastric perforator (DIEP) Flap. There is a general consensus in current literature regarding the difficulty for curative treatment in angiosarcomas. There is a requirement for surgical intervention to be aggressive to ensure oncological clearance. Subsequently, the extensive reconstructive task proves a major procedure for any plastic surgeon. DIEP autologous flap chest wall reconstruction accompanying radical mastectomy can be used in efforts to eradicate risks of deep margin incomplete excision in breast angiosarcomas. This case report and review of the current literature aim to provide guidance for colleagues managing angiosarcomas and also highlight the versatility of the DIEP flap.

Defining clinicopathological and radiological features of breast cancer in women under the age of 35: an epidemiological study.

INTRODUCTION: Breast cancer is the most commonly diagnosed female cancer. Diagnosis in younger women (under 35 years) is different to their older counterparts, and mammography is not considered as sensitive in this cohort. Consequentially, younger patients may present later with more advanced disease. METHODS: This is a retrospective analysis of a prospectively updated database containing consecutive patients who presented to the symptomatic breast unit of Galway University Hospital between 2009 and 2015. Patient clinicopathologic factors, clinical examination features, diagnostic radiological modalities and Bi-RADS score were all assessed. Data was analysed using Statistical Package for the Social Sciences version 25. RESULTS: One thousand eight hundred thirty-six patients were diagnosed with breast cancer, and of these, 51 (2.8%) patients were < 35 years. Invasive ductal carcinoma made up 90% of diagnosis, and 42% had an associated ductal carcinoma in situ. Fifty-four percent were high-grade tumours and 52% presented with stage III disease or greater. The main radiological tool used was ultrasound, which had a sensitivity of 87.50% (95% confidence interval [CI] 74.75 to 95.27%). Mammogram sensitivity was 86.84% (95% CI 71.91 to 95.59%). Magnetic resonance imaging was used in 29% of cases, with a sensitivity of 100.00% (95% CI 78.20 to 100.00%). CONCLUSION: Females under 35 tend to be diagnosed with aggressive, advanced stage tumours. Ultrasound remains the radiological test of choice, although diagnosis using mammography demonstrated a relatively high sensitivity compared with previous reports. This study emphasises the varying epidemiology of breast cancer in younger patients and the potential role of mammography in making radiological diagnosis in those who are symptomatic.

A Review of the Impact of Neoadjuvant Chemotherapy on Breast Surgery Practice and Outcomes.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced breast cancer as it facilitates breast conserving surgery (BCS) and allows surgical treatment of patients considered inoperable at baseline. The aim of this study was to assess the trends in breast cancer management with regard to the administration of NAC and adjuvant chemotherapy and the effect this has on surgical practice, patient outcomes, and patterns of disease recurrence. PATIENTS AND METHODS: Patients treated with chemotherapy from 2005 to 2014 were identified from a prospectively maintained database. Clinicopathologic details, timing of chemotherapy delivery, and surgical procedures carried out were analyzed. RESULTS: A total of 1619 patients were included in the study. The NAC group (n = 383) had a higher T stage (P < .001) and higher grade disease than the adjuvant group (P = .017). Luminal A breast cancer was less likely to be treated by NAC. The proportion of patients treated with NAC has increased from 12.1% in 2005 to 48.3% in 2014 (P < .001). There was an increase in the BCS rate over time (P = .002); however, a higher proportion of the neoadjuvant group (55.5%) underwent mastectomy. Timing of chemotherapy influenced the type of reconstructive procedure carried out (P = .003). CONCLUSION: The number of patients with breast cancer being treated with NAC is increasing, which is influencing the increasing rate of BCS, though mastectomy is still central to the surgical management of those in receipt of NAC.

The changing cost of breast cancer care: lessons from a centralised modern cancer centre.

BACKGROUND: The cost of new cancer technologies has been the subject of intense debate in recent years. There have been significant advances in therapeutic techniques for breast cancer over the past 20 years. This has been accompanied by the concentration of services in designated cancer centres. The aim of this study was to examine the changing cost of breast cancer management over an 18-year period and identify factors underlying this. METHODS: We use breast cancer services data from Galway University Hospital in 1995-1996, 2005-2006 and 2011-2012 to examine the changing pattern of care costs and survival. RESULTS: The number of patients treated for breast cancer rose from 200 in 1995-1996, to 411 in 2005-2006 and 563 in 2011-2012. Two-year survival rose in line with national figures from 84 to 89.78 and 92.07%, in the three-time periods respectively. Adjusting for inflation, the average cost per patient rose from €14,710 (95% C.I., €13,398 to €16,022) in 1995-1996 to €30,405 (95% C.I., €38,620 to €32,189) in 2005-2006, before falling to €14,458 (C.I., €13,343 to €15,572) in 2011-2012. We found significant changes in the pattern of costs, with some rising in relative and absolute terms while others fell as new therapies became available and/or moved off patent. CONCLUSION: Within an evolving context where services are centralised, new therapies emerge and subsequently come off patent, our understanding of the value of cancer therapies continues to evolve. This has important implications for the evaluation of new therapies and broader policy initiatives in this area.

The Impact of Surgical Complications on Cancer Recurrence Rates: A Literature Review.

INTRODUCTION: The inflammatory response to a post-operative infection can increase the risk of tumour recurrence in cancer through the release of pro-inflammatory mediators. The aim of this study was review the literature to assess the relationship between post-operative complications and cancer recurrence. METHODS: We performed a literature review of the mechanism of such an association and looked at evidence in different cancer subtypes. RESULTS: A relationship has been identified for many cancer subtypes, and multiple theories have been proposed for the mechanism of this association. Methods to reduce post-operative complications may impact positively on cancer recurrence rates. CONCLUSION: This review demonstrates that wound complications after surgery can have significant implications for cancer patients. Strategies are required to minimize the risk of post-operative wound complications in patients undergoing cancer resection.

Differential impact of hormone receptor status on survival and recurrence for HER2 receptor-positive breast cancers treated with Trastuzumab.

INTRODUCTION: Hormone receptor status has major implications for treatment and survival of breast cancer. Yet the impact of hormone receptor status on outcome after Trastuzumab has received little attention. The objective here was to explore any differential effects of Trastuzumab treatment (Trast +ve) on Luminal B HER2 or HER2+(ER-) breast cancer subtypes. METHODS: A cohort of 469 HER2 receptor-positive breast cancers was categorised by molecular subtype and Trastuzumab treatment. Effects of Trastuzumab treatment on survival, locoregional recurrence and distant metastasis were investigated by subtype, using univariate and multivariate analysis. RESULTS: Trast +ve Luminal B HER2 patients had significant improvements in 5-year DFS (p < 0.001) and OS (p < 0.001), while Trast +ve HER2+(ER-) patients had significant improvements in 5-year DFS (p = 0.012) alone. Only Trast +ve Luminal B HER2 cancers displayed a significant reduction in LRR rates (p < 0.001). A significant reduction in distant metastasis rates was seen in Trast +ve Luminal B HER2 (p < 0.001) and HER2+(ER-) (p = 0.009) cancers. Interestingly, bone metastasis rates in Trast +ve Luminal B HER2 cancers demonstrated the greatest reduction (36.2-6.7%). Multivariate analysis of Trast +ve patients found no difference in distant metastasis rates (p = 0.96) between subtypes. Significantly, lower LRR rates were seen in Trast +ve Luminal B HER2 cancers, compared to Trast +ve HER2+(ER-) (p = 0.018). CONCLUSION: An enhanced response to Trastuzumab was seen in Luminal B HER2 cancers. We highlight how Trastuzumab treatment changed the natural history of the HER2 receptor-positive breast cancer, demonstrating improved efficacy in changing the outcome of hormone receptor-positive patients.

An Appraisal of Inflammatory Markers in Distinguishing Acute Uncomplicated and Complicated Appendicitis.

BACKGROUND: It remains difficult to distinguish between complicated appendicitis (CAP) and uncomplicated appendicitis (UAP). There is a paucity of studies utilizing inflammatory markers to stratify the severity of acute appendicitis. This study aimed to evaluate and demonstrate the potential clinical utility of inflammatory markers as adjuncts in distinguishing CAP and UAP. METHODS: A comparative observational study was performed. Patients diagnosed with acute appendicitis were categorized as (a) complicated (necrosis, perforation, abscess) and (b) uncomplicated (inflamed, edematous). Hematological indices were combined to generate the following ratios: white cell lymphocyte ratio (WLR), white cell neutrophil ratio (WNR) and neutrophil lymphocyte ratio (NLR). Parameter accuracy was assessed using summary receiver operating characteristic (sROC) curves, classification and regression tree analysis and confusion matrix generation. RESULTS: On sROC analysis, neutrophils (area under the curve (AUC) 0.79, p < 0.001), WLR (AUC 0.79, p < 0.001) and NLR (AUC 0.79, p < 0.001) were the most accurate parameters in distinguishing CAP and UAP. White cell count (WCC; AUC 0.76, p < 0.001) and C-reactive protein (AUC 0.75, p < 0.001) were less accurate. WCC >12.25 (sensitivity 70%, specificity 68%) and NLR >5.47 (sensitivity 78%, specificity 70%) were the most accurate in identifying CAP. CONCLUSION: Inflammatory marker cutoff points can be generated and utilized to differentiate between UAP and CAP. This may be useful when deciding between conservative and operative management.

Diagnostic dilemmas due to fish bone ingestion: Case report & literature review.

INTRODUCTION: The diagnosis of abdominal complications due to fish bone ingestion is particularly difficult as the presentation may mimic common abdominal pathologies. PRESENTATION OF CASE: 65 year-old male presented with a two day history of right iliac fossa pain. He denied any nausea and vomiting. He had no systemic systems including fever, change in bowel habit. He had tenderness and guarding localized to the right iliac fossa. He had raised inflammatory markers. A CT scan of the abdomen was performed which showed fat standing in proximity to the terminal ileum, with the appearance of Crohn's disease. The clinical picture did not match the imaging and so the patient underwent a diagnostic laparoscopy. Findings included an acutely inflamed terminal ileum. A foreign body was identified piercing through at the small bowel wall at the terminal ileum. The foreign body was removed and revealed a fish bone. Intracorporeal sutures were inserted at the site of the microperforation. The patient was discharged well two days post operatively. DISCUSSION: Fish bone perforation is not a common cause of gastrointestinal perforation. Unfortunately the history is often non-specific and these people can be misdiagnosed with acute appendicitis & other pathologies. CT scans can be useful to aid diagnostics. It is not however fully sensitive in detecting complications arising from fishbone ingestion. CONCLUSION: Management therefore, should be based taking into account primarily the clinical picture & may necessitate diagnostic laparoscopy.

Effects of age on the detection and management of breast cancer.

Currently, breast cancer affects approximately 12% of women worldwide. While the incidence of breast cancer rises with age, a younger age at diagnosis is linked to increased mortality. We discuss age related factors affecting breast cancer diagnosis, management and treatment, exploring key concepts and identifying critical areas requiring further research. We examine age as a factor in breast cancer diagnosis and treatment relating it to factors such as genetic status, breast cancer subtype, hormone factors and nodal status. We examine the effects of age as seen through the adoption of population wide breast cancer screening programs. Assessing the incidence rates of each breast cancer subtype, in the context of age, we examine the observed correlations. We explore how age affects patient's prognosis, exploring the effects of age on stage and subtype incidence. Finally we discuss the future of breast cancer diagnosis and treatment, examining the potential of emerging tests and technologies (such as microRNA) and how novel research findings are being translated into clinically relevant practices.