Value of a 21-gene expression assay on core biopsy to predict neoadjuvant chemotherapy response in breast cancer: systematic review and meta-analysis.

BACKGROUND: A recurrence score based on a 21-gene expression assay predicts the benefit of adjuvant chemotherapy in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This systematic review aimed to determine whether the 21-gene expression assay performed on core biopsy at diagnosis predicted pathological complete response (pCR) to neoadjuvant chemotherapy. METHODS: The study was performed according to PRISMA guidelines. Relevant databases were searched to identify studies assessing the value of the 21-gene expression assay recurrence score in predicting response to neoadjuvant chemotherapy in patients with breast cancer. The Newcastle-Ottawa Scale was used to assess the quality of the studies. Results are reported as risk ratio (RR) with 95 per cent confidence interval using the Cochrane-Mantel-Haenszel method for meta-analysis. Sensitivity analyses were carried out where appropriate. RESULTS: Seven studies involving 1744 patients reported the correlation between pretreatment recurrence score and pCR. Of these, 777 patients (44.6 per cent) had a high recurrence score and 967 (55.4 per cent) a low-intermediate score. A pCR was achieved in 94 patients (5.4 per cent). The pCR rate was significantly higher in the group with a high recurrence score than in the group with a low-intermediate score (10.9 versus 1.1 per cent; RR 4.47, 95 per cent c.i. 2.76 to 7.21; P < 0.001). A significant risk difference was observed between the two groups (risk difference 0.10, 0.04 to 0.15; P = 0.001). CONCLUSION: A high recurrence score is associated with higher pCR rates and a low-intermediate recurrence score may indicate chemoresistance. Routine assessment of recurrence score by the 21-gene expression assay on core biopsy might be of value when considering neoadjuvant chemotherapy in patients with ER-positive, HER2-negative breast cancer.

Meta-analysis of the impact of progesterone receptor status on oncological outcomes in oestrogen receptor-positive breast cancer.

BACKGROUND: Assessment of the oestrogen receptor (ER) provides important prognostic information in breast cancer. The impact of progesterone receptor (PgR) status is less clear. Standardization of immunohistochemical analysis of these receptors has reduced interstudy heterogeneity. The aim of this meta-analysis was to evaluate the impact of PgR negativity on outcomes in ER-positive (ER+) breast cancer. METHODS: This study was performed according to PRISMA and MOOSE guidelines. PubMed, Embase and the Cochrane Library were searched systematically to identify studies comparing disease-free survival as the primary outcome and overall survival as secondary outcome between PgR-positive (PgR+) and PgR-negative (PgR-) status in ER+ breast cancer. A meta-analysis of time-to-effect measures from included studies was undertaken. RESULTS: Eight studies including 13 667 patients, 11 838 in the ER+PgR+ group and 1829 in the ER+PgR- group, met the inclusion criteria. Treatment characteristics did not differ significantly between the two groups. Patients in the ER+PgR- group had a higher risk of disease recurrence than those who had ER+PgR+ disease (hazard ratio (HR) 1·57, 95 per cent c.i. 1·38 to 1·79; P < 0·001). This hazard was increased in patients with human epidermal growth factor receptor 2-negative tumours (HR 1·62, 1·37 to 1·93; P < 0·001). A similar result was observed for overall survival (HR 1·69, 1·33 to 2·14; P < 0·001). CONCLUSION: PgR negativity is associated with significant reductions in disease-free and overall survival in ER+ breast cancer. Treatment and surveillance strategies in these patients should be tailored accordingly.

ANTECEDENTES: La evaluación del receptor de estrógenos (oestrogen receptor, ER) proporciona una importante información pronóstica en el cáncer de mama. El impacto de del estado del receptor de la progesterona (progesterone receptor, PgR) está menos claro. La estandarización del análisis inmunohistoquímico de estos receptores ha reducido la heterogeneidad entre los estudios. El objetivo de este metaanálisis fue evaluar el impacto de la negatividad de PgR (PgR-) en los resultados del cáncer de mama ER positivo (ER+). MÉTODOS: Este estudio se realizó de acuerdo con las directrices PRISMA/MOOSE. Se llevó a cabo una búsqueda sistemática en MEDLINE, PubMed y biblioteca Cochrane para identificar estudios que comparasen la supervivencia libre de enfermedad (disease free survival, DFS) como resultado primario y la supervivencia global (overall survival, OS) como resultado secundario entre los estados PgR+ y PgR- en el cáncer de mama ER+. Se realizó un metaanálisis de los estudios incluidos de las medidas de tiempo hasta el efecto. RESULTADOS: Ocho estudios que incluían 13.533 pacientes, 11.724 en el grupo ER+PgR+ y 1.809 en el grupo ER+PgR- cumplieron con los criterios de inclusión. Las características del tratamiento no diferían significativamente entre los dos grupos. Los pacientes en el grupo ER+PgR- presentaron un riesgo más elevado de recidiva de la enfermedad que aquellas que tenían enfermedad ER+PgR+ (DFS, cociente de riesgos instantáneos, hazard ratio, HR 1,57; i.c. del 95% 1,38-1,79; P < 0,001). Este riesgo se incrementó en pacientes que eran HER2 negativo (DFS HR 1,62; i.c. del 95% 1,37-1,93; P < 0,001). Un resultado similar se observó para la OS (HR 1,69; i.c. del 95% 1,33-2,14, P < 0,001). CONCLUSIÓN: La negatividad de PgR se asocia con disminuciones significativas de DFS y OS en el cáncer de mama ER+. En estas pacientes, las estrategias de tratamiento y seguimiento en deberán adecuarse a cada caso particular.

Systematic review and meta-analysis comparing primary resection and anastomosis versus Hartmann's procedure for the management of acute perforated diverticulitis with generalised peritonitis.

BACKGROUND: Surgical strategies for acute perforated diverticulitis with generalised peritonitis remain controversial. This study aimed to meta-analyse trials comparing primary resection and anastomosis (PRA) to Hartmann's procedure (HP) for Hinchey III/IV diverticulitis. METHODS: A systematic literature search was conducted to identify observational studies and randomised control trials (RCTs) of patients with Hinchey III/IV diverticulitis undergoing sigmoidectomy that compared PRA to HP. The methodological quality of the included studies was assessed systematically (Newcastle-Ottawa, Jadad and Cochrane risk of bias scores) and a meta-analysis was performed. RESULTS: After removal of duplicates, 12 studies including 4 RCTs were identified. The analysis included 918 patients, of whom 367 (39.98%) underwent PRA. Both the initial stoma rate (risk ratio [RR] persistent stoma 0.43, 95% confidence interval [CI] 0.26, 0.71, p = 0.001; I2 = 99%, p < 0.0001) and the rate of permanent stoma after combining the first (emergency surgery) and second (stoma reversal) procedures were lower in the PRA group. There was no difference in in 30-day mortality; however, PRA resulted in a reduction in overall mortality as well as major complications after the initial operation (RR 0.67, 95% CI 0.46, 0.97, p = 0.03; I2 = 22%, p = 0.26), stoma reversal (RR 0.48, 95% CI 0.26, 0.92, p = 0.03; I2 = 0%, p = 0.58) and when combining both procedures (RR 0.67, 95% CI 0.51, 0.88, p = 0.005; I2 = 0%, heterogeneity p = 0.58). A subgroup analysis of stoma reversal rates using data from only RCTs were consistent (RR permanent stoma, 0.33, 95% CI 0.13, 0.85, p = 0.02; I2 = 77%, p = 0.004) with the findings of the overall analysis. CONCLUSIONS: This meta-analysis demonstrates that PRA used in the management of haemodynamically stable patients with Hinchey grade III/IV diverticulitis leads to a lower overall persistent stoma rate, with reduced morbidity compared with the traditional management.

Merkel Cell Carcinoma: A Case Series

Introduction Merkel cell carcinoma (MCC) is a rare cutaneous tumour that is clinically aggressive with a high local, regional, and distant metastatic potential. Cases Three male patients presented to University Hospital Limerick (UHL) in 2015 with cutaneous lesions of the thorax, buttock and forearm. Once MCC was confirmed, management included surgical wide local excision (WLE) with regional lymph node dissection followed by adjuvant radiotherapy. One patient is in remission. The second has residual locoregional lymph node disease and is undergoing annual CT surveillance. The third had distant metastatic disease and is deceased from an unrelated condition. Discussion This case series highlights the presentation and management of MCC. We also discus relevant guidelines. The management of MCC is complex and there is a need to establish local or national databases to identify and monitor patients with MCC.

C-reactive protein as a predictor of anastomotic leak in the first week after anterior resection for rectal cancer.

AIM: Anastomotic leak (AL) after anterior resection results in increased morbidity, mortality and local recurrence. The aim of this study was to assess the ability of C-reactive protein (CRP) to predict AL in the first week after anterior resection for rectal cancer. METHOD: A retrospective review of a prospectively maintained database that included all patients undergoing anterior resection between January 2008 and December 2013 was performed. The ability of CRP to predict AL was assessed using area under the receiver-operating characteristics (AUC) curves. The severity of AL was defined using the International Study Group of Rectal Cancer (ISREC) grading system. RESULTS: Two-hundred and eleven patients were included in the study. Statistically significant differences in mean CRP values were found between those with and without an AL on postoperative days 5, 6 and 7. A CRP value of 132 mg/l on postoperative day 5 had an AUC of 0.75, corresponding to a sensitivity of 70%, a specificity of 76.6%, a positive predictive value of 16.3% and a negative predictive value of 97.5%. Multivariable analysis found that a CRP of > 132 mg/l on postoperative day 5 was the only statistically significant patient factor that was linked to an increased risk of AL (HR = 8.023, 95% CI: 1.936-33.238, P = 0.004). CONCLUSION: Early detection of AL may minimize postoperative complications. CRP is a useful negative predictive test for the development of AL following anterior resection.

The impact of the Biomolecular Era on breast cancer surgery.

Surgery has always played a central role in the management of breast cancer, with local control via complete tumour resection long established as the cornerstone of effective breast cancer therapy. While extensive surgical resection in the form of the Halstead radical mastectomy dominated treatment up until at least the 1970s, the advent of adjuvant loco-regional and systemic therapies has resulted in a decrease in the magnitude of surgical intervention in recent decades. The Biomolecular or "-omics" era initiated with the discovery of the DNA double helix in 1953 and intensified by the completion of the human genome project in 2003 has seen an unprecedented expansion in our understanding of the molecular and genetic heterogeneity of cancer. This review will discuss how the clinical application of this knowledge in the direction of personalised risk assessment and breast cancer treatment has significant implications for modern surgical practice.

Investigation of 7-dehydrocholesterol reductase pathway to elucidate off-target prenatal effects of pharmaceuticals: a systematic review.

Mendelian diseases contain important biological information regarding developmental effects of gene mutations that can guide drug discovery and toxicity efforts. In this review, we focus on Smith-Lemli-Opitz syndrome (SLOS), a rare Mendelian disease characterized by compound heterozygous mutations in 7-dehydrocholesterol reductase (DHCR7) resulting in severe fetal deformities. We present a compilation of SLOS-inducing DHCR7 mutations and the geographic distribution of those mutations in healthy and diseased populations. We observed that several mutations thought to be disease causing occur in healthy populations, indicating an incomplete understanding of the condition and highlighting new research opportunities. We describe the functional environment around DHCR7, including pharmacological DHCR7 inhibitors and cholesterol and vitamin D synthesis. Using PubMed, we investigated the fetal outcomes following prenatal exposure to DHCR7 modulators. First-trimester exposure to DHCR7 inhibitors resulted in outcomes similar to those of known teratogens (50 vs 48% born-healthy). DHCR7 activity should be considered during drug development and prenatal toxicity assessment.

A Positive Node on Ultrasound-Guided Fine Needle Aspiration Predicts Higher Nodal Burden Than a Positive Sentinel Lymph Node Biopsy in Breast Carcinoma.

INTRODUCTION: Axillary status remains an important prognostic indicator in breast cancer. Certain patients with a positive sentinel node (SLNB) may not benefit from axillary clearance (AC). Uncertainty remains if this approach could be applied to patients diagnosed with axillary metastases on ultrasound-guided fine needle aspiration cytology (USFNAC). The aim of this study was to compare nodal burden in patients with positive USFNAC and a positive SLNB. METHODS: A retrospective study was performed involving all BC patients between 2007 and 2014 who had either pre-operative USFNAC or a SLNB. Patient/tumour characteristics and nodal burden were examined in all patients proceeding to AC. RESULTS: 974 patients were eligible for analysis. 439 patients (45 %) had positive USFNAC and 535 (55 %) had a positive SLNB. USFNAC-positive patients were more likely to undergo mastectomy (Chi-square test; p < 0.001), have extra-nodal extension (p < 0.001), be oestrogen receptor negative (p < 0.001) and be HER2 positive (p < 0.001). The median total number of lymph nodes (LNs) excised during AC was higher in the USFNAC group (Mann-Whitney test; 23 vs. 21; p < 0.001). The median total number of involved LNs was 3 (range 1-47) in FNAC-positive patients versus 1 (range 1-37) in SLNB-positive patients (p < 0.001). The median number of involved LNs in level 1 was 3 in FNAC-positive patients versus 1 in SLNB-positive patients (p < 0.001). Within the SLN-positive group, 49 % of the patients had only one involved LN, 28 % had two nodes involved and 23 % had ≥3. In comparison, within the FNAC-positive group only 13 % of the patients had one involved LN, 12 % had two nodes involved and 74 % had ≥3. CONCLUSION: Patients with positive USFNAC have more aggressive clinico-pathological characteristics and higher nodal burden compared to SLNB-positive patients. Currently, the authors advocate that patients not receiving neoadjuvant chemotherapy, with a positive USFNAC, should proceed directly to an axillary ALND.

Does motor block related to long-acting brachial plexus block cause patient dissatisfaction after minor wrist and hand surgery? A randomized observer-blinded trial.

BACKGROUND: Patient dissatisfaction has been previously associated with motor block in shoulder surgery patients receiving brachial plexus block. For elective minor wrist and hand surgery, we tested whether a regional block accelerating the early return of upper extremity motor function would improve patient satisfaction compared with a long-acting proximal brachial plexus block. METHODS: A total of 177 patients having elective 'minor' wrist and hand surgery under awake regional block randomly received adrenalized infraclavicular lidocaine 2% 10 ml+ropivacaine 0.75% 20 ml ('long acting', n=90), or adrenalized infraclavicular lidocaine 1.5% 30 ml+long-acting distal median, radial, and ulnar nerve blocks selected according to the anticipated area of postoperative pain ('short acting', n=87). A blinded observer questioned patients on day 1 for numerically rated (0-10) subjective outcomes. RESULTS: With 95% power, there was no evidence for a 1-point satisfaction shift in the short acting group: satisfaction was similarly high for both groups [median (inter-quartile range)=10 (8-10) vs 10 (8-10), P=0.71], and also demonstrated strong evidence for equivalence [mean difference (95% confidence interval)=-0.18 (-0.70 to 0.35)]. There was no difference between the groups for weakness- or numbness-related dissatisfaction (low for both groups), or for numerically rated or time to first pain. Surgical anaesthesia success was similar between the groups (short acting, 97% vs 93%, P=0.50), although more patients in the short acting group had surgery initiated in ≤25 min (P=0.03). CONCLUSIONS: Patient satisfaction is not improved after elective minor wrist and hand surgery with a regional block accelerating the early return of motor function. For this surgery, motor block related to a long-acting brachial plexus block does not appear to cause patient dissatisfaction. Clinical Trial Registration number. ACTRN12610000749000, https://www.anzctr.org.au/registry/trial_review.aspx?ID=335931.

Acute complicated appendicitis caused by an ingested toothpick - A case report.

INTRODUCTION AND IMPORTANCE: Acute appendicitis is one of the most common presentations to the emergency department, particularly in young adults. A combination of clinical suspicion, inflammatory blood markers and imaging modalities such as ultrasound and CT are used for its definitive diagnosis. Early detection and intervention are paramount to reduce morbidity and mortality. Laparoscopic appendicectomy is the current gold standard in the management of appendicitis, especially if complicated according to EAES guidelines. There are few documented cases in the literature of acute appendicitis secondary to foreign body ingestion. On account of this, there are currently no guidelines for its management. Our literature review highlights the importance of surgical management of foreign body acute appendicitis. CASE PRESENTATION: This case report describes the rare presentation of acute complicated appendicitis caused by an ingested toothpick in a 64 year old woman. The patient was admitted with a 3 day history of lower abdominal pain, localizing to the right iliac fossa with raised inflammatory markers. CT imaging reported acute complicated appendicitis. Laparoscopic appendicectomy was performed during which a toothpick was seen protruding through the appendiceal wall. Post operatively the patient was treated with IV antibiotics for 5 days prior to discharge. CLINICAL DISCUSSION: Due to the rare nature of foreign body appendicitis there are no specific guidelines on the respective surgical approach. A literature review showed that in the setting of foreign body appendicitis, surgical intervention is paramount with no scope for conservative management. CONCLUSION: Surgical approach is based on the clinical judgement and skillset of the operating surgeon.

Concomitant infraclavicular plus distal median, radial, and ulnar nerve blockade accelerates upper extremity anaesthesia and improves block consistency compared with infraclavicular block alone.

BACKGROUND: This prospective, randomized, observer-blinded study tested the hypothesis that a combined ultrasound-guided block of the infraclavicular brachial plexus plus distal median, radial, and ulnar nerves would accelerate upper extremity anaesthesia compared with infraclavicular block alone. METHODS: Elective wrist and hand surgery patients were randomly assigned to receive 42 ml infraclavicular lidocaine 1.5% with epinephrine 1/200,000 ('infraclavicular only'; n=30) or 30 ml lidocaine 1.5% with epinephrine 1/200,000 followed by a distal median, radial, and ulnar nerve block using 12 ml 50:50 lidocaine 2%+ropivacaine 0.75% ('combined'; n=31). A blinded observer assessed pinprick sensory and motor block in the four distal nerve territories at 10 and 15 min (each nerve/parameter: no block, 3, to complete block, 0). RESULTS: Total aggregate block score (sensory+motor) was reduced in the combined group at 15 min [mean (95% confidence interval)=6.7 (5.3-8.1) vs. 9.9 (7.9-11.9), mean difference (95% confidence interval)=3.2 (0.81-5.6), P=0.01], and corresponded to an estimated onset effect time benefit of 6 min (∼40% treatment effect). The combined group also demonstrated reduced variance about the mean (sd=3.7 vs. 5.4, P=0.046). Mean (sd) total block score (sensory+motor) was significantly reduced at 15 min in the combined group for each individual nerve [median, radial, ulnar, respectively: 1.4 (1.1) vs. 2.4 (1.5), P=0.005; 1.2 (1.1) vs. 2.0 (1.5), P=0.03; 1.6 (1.3) vs. 2.5 (1.6), P=0.03]. CONCLUSIONS: At an approximately equivalent total local anaesthetic dose, a combined infraclavicular block plus distal median, radial, and ulnar nerve blockade accelerates anaesthesia onset time and improves block consistency compared with an infraclavicular block alone. CLINICAL TRIALS REGISTRY: ANZCTR: ACTRN12610000155099. https://www.anzctr.org.au/registry/trial_review.aspx?ID=335162.

Clinical utility of the 21-gene assay in predicting response to neoadjuvant endocrine therapy in breast cancer: A systematic review and meta-analysis.

INTRODUCTION: OncotypeDX© Recurrence Score (RS) is a multigene panel used to aid therapeutic decision making in early-stage, estrogen receptor positive (ER+)/human epidermal growth factor receptor-2 negative (HER2-) breast cancer. AIM: To compare responses to neoadjuvant endocrine therapy (NET) in patients with ER+/HER2-breast cancer following substratification by RS testing. METHODS: This systematic review was performed in accordance to the PRISMA guidelines. Studies evaluating pathological complete response (pCR), partial response (PR), and successful conversion to breast conservation surgery (BCS) rates following NET guided by RS were retrieved. Dichotomous outcomes were reported as odds ratios (ORs) with 95% confidence intervals (CIs) following estimation by Mantel-Haenszel method. RESULTS: Eight prospective studies involving 691 patients were included. The mean age was 62.6 years (range 25-85) and the mean RS was 14.5 (range 0-68). Patients with RS < 25 (OR: 4.60, 95% CI: 2.53-8.37, P < 0.001) and RS < 30 (OR: 3.40, 95% CI: 1.96-5.91, P < 0.001) were more likely to achieve PR than their counterparts. NET prescription failed to increase BCS conversion rates for patients with RS < 18 (OR: 0.23, 95% CI: 0.04-1.47, P = 0.120) and RS > 30 (OR: 1.27, 95% CI: 0.64-2.49, P = 0.490) respectively. Only 22 patients achieved pCR (2.8%) and RS group failed to predict pCR following NET (P = 0.850). CONCLUSION: Estimations from this analysis indicate that those with low-intermediate RS on core biopsy are four times more likely to respond to NET than those with high-risk RS. Performing RS testing on diagnostic biopsy may be useful in guiding NET prescription.

Is radiomic MRI a feasible alternative to OncotypeDX® recurrence score testing? A systematic review and meta-analysis.

BACKGROUND: OncotypeDX® recurrence score (RS) aids therapeutic decision-making in oestrogen-receptor-positive (ER+) breast cancer. Radiomics is an evolving field that aims to examine the relationship between radiological features and the underlying genomic landscape of disease processes. The aim of this study was to perform a systematic review of current evidence evaluating the comparability of radiomics and RS. METHODS: A systematic review was performed as per PRISMA guidelines. Studies comparing radiomic MRI tumour analyses and RS were identified. Sensitivity, specificity and area under curve (AUC) delineating low risk (RS less than 18) versus intermediate-high risk (equal to or greater than 18) and low-intermediate risk (RS less than 30) and high risk (RS greater than 30) were recorded. Log rate ratios (lnRR) and standard error were determined from AUC and 95 per cent confidence intervals. RESULTS: Nine studies including 1216 patients met inclusion criteria; the mean age at diagnosis was 52.9 years. Mean RS was 16 (range 0-75); 401 patients with RS less than 18, 287 patients with RS 18-30 and 100 patients with RS greater than 30. Radiomic analysis and RS were comparable for differentiating RS less than 18 versus RS 18 or greater (RR 0.93 (95 per cent c.i. 0.85 to 1.01); P = 0.010, heterogeneity (I2)=0%) as well as RS less than 30 versus RS 30 or greater (RR 0.76 (95 per cent c.i. 0.70 to 0.83); P < 0.001, I2=0%). MRI sensitivity and specificity for RS less than 18 versus 18 or greater was 0.89 (95 per cent c.i. 0.85 to 0.93) and 0.72 (95 per cent c.i. 0.66 to 0.78) respectively, and 0.79 (95 per cent c.i. 0.72 to 0.86) and 0.74 (95 per cent c.i. 0.68 to 0.80) for RS less than 30 versus 30 or greater. CONCLUSION: Radiomic tumour analysis is comparable to RS in differentiating patients into clinically relevant subgroups. For patients requiring MRI, radiomics may complement and enhance RS for prognostication and therapeutic decision making in ER+ breast cancer.

Disease recurrence and oncological outcome of patients treated surgically with curative intent for estrogen receptor positive, lymph node negative breast cancer.

BACKGROUND: The molecular era has identified four breast cancer subtypes. Luminal A breast cancer (LABC) is defined by estrogen-receptor positive (ER+), progesterone-receptor positive (PgR+) and human epidermal growth factor receptor-2 negative (HER2-) tumours; these cancers are the most common and carry favourable prognoses. AIMS: To describe clinicopathologic features, oncological outcome and relapse patterns in LABC. METHODS: Consecutive female patients diagnosed with ER/PgR+/HER2-, lymph node negative (LN-) breast cancer between 2005 and 2015 were included. Clinicopathological and recurrence data was recorded using descriptive statistics. Oncological outcome was determined using Kaplan-Meier and Cox-regression analyses. RESULTS: Analysis was performed for 849 patients with median follow-up of 102.1 months. Mean disease-free (DFS) and overall survival (OS) were 85.8% and 91.8%. Seventy patients died during this study (8.2%), while 58 patients had recurrence; 7 had local recurrence (0.8%) and 51 had distant recurrence (DDR) (6.0%). Patients developing DDR were likely to be postmenopausal (P = 0.028), present symptomatically (P < 0.001) and have larger tumours (P < 0.001). The mean time to DDR was 65.7 months, with fatal recurrence occurring in 66.6% of patients with DDR (34/51). Systemic chemotherapy prescription did not influence DDR (P = 0.053). Age >65 (hazards ratio (HR):1.66, 95% Confidence Interval (CI):1.07-2.55, P = 0.022), presenting symptomatically (HR:2.28, 95%CI:1.21-4.29, P = 0.011) and tumour size >20 mm (HR:1.81, 95%CI:1.25-2.62, P = 0.002) predicted DFS, while age>65 (HR:2.60, 95%CI:1.49-4.53, P = 0.001) and being postmenopausal at diagnosis (HR:3.13, 95%CI:1.19-8.22, P = 0.020) predicted OS. CONCLUSION: Our series demonstrated excellent survival outcomes for patients diagnosed with LN- LABC after almost a decade of follow-up. However, following DDR, fatal progression is often imminent.

Optimal reconstructive strategies in the setting of post-mastectomy radiotherapy - A systematic review and network meta-analysis.

BACKGROUND: A third of breast cancer patients require mastectomy. In some high-risk cases postmastectomy radiotherapy (PMRT) is indicated, threatening reconstructive complications. Several PMRT and reconstruction combinations are used. Autologous flap (AF) reconstruction may be immediate (AF→PMRT), delayed-immediate with tissue expander (TE [TE→PMRT→AF]) or delayed (PMRT→AF). Implant-based breast reconstruction (IBBR) includes immediate TE followed by PMRT and conversion to permanent implant (PI [TE→PMRT→PI]), delayed TE insertion (PMRT→TE→PI), and prosthetic implant conversion prior to PMRT (TE→PI→PMRT). AIM: Perform a network metanalysis (NMA) assessing optimal sequencing of PMRT and reconstructive type. METHODS: A systematic review and NMA was performed according to PRISMA-NMA guidelines. NMA was conducted using R packages netmeta and Shiny. RESULTS: 16 studies from 4182 identified, involving 2322 reconstructions over three decades, met predefined inclusion criteria. Studies demonstrated moderate heterogeneity. Multiple comparisons combining direct and indirect evidence established AF-PMRT as the optimal approach to avoid reconstructive failure, compared with IBBR strategies (versus PMRT→TE→PI; OR [odds ratio] 0.10, CrI [95% credible interval] 0.02 to 0.55; versus TE→PMRT→PI; OR 0.13, CrI 0.02 to 0.75; versus TE→PI→PMRT OR 0.24, CrI 0.05 to 1.05). PMRT→AF best avoided infection, demonstrating significant improvement versus PMRT→TE→PI alone (OR 0.12, CrI 0.02 to 0.88). Subgroup analysis of IBBR found TE→PI→PMRT reduced failure rates (OR 0.35, CrI 0.15-0.81) compared to other IBBR strategies but increased capsular contracture. CONCLUSION: Immediate AF reconstruction is associated with reduced failure in the setting of PMRT. However, optimal reconstructive strategy depends on patient, surgeon and institutional factors. If IBBR is chosen, complication rates decrease if performed prior to PMRT. PROSPERO REGISTRATION: CRD 42020157077.

The impact of progesterone receptor negativity on oncological outcomes in oestrogen-receptor-positive breast cancer.

BACKGROUND: Oestrogen receptor (ER) status provides invaluable prognostic and therapeutic information in breast cancer (BC). When clinical decision making is driven by ER status, the value of progesterone receptor (PgR) status is less certain. The aim of this study was to describe clinicopathological features of ER-positive (ER+)/PgR-negative (PgR-) BC and to determine the effect of PgR negativity in ER+ disease. METHODS: Consecutive female patients with ER+ BC from a single institution were included. Factors associated with PgR- disease were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analysis. RESULTS: In total, 2660 patients were included with a mean(s.d.) age of 59.6(13.3) years (range 21-99 years). Median follow-up was 97.2 months (range 3.0-181.2). Some 2208 cases were PgR+ (83.0 per cent) and 452 were PgR- (17.0 per cent). Being postmenopausal (odds ratio (OR) 1.66, 95 per cent c.i. 1.25 to 2.20, P < 0.001), presenting with symptoms (OR 1.71, 95 per cent c.i. 1.30 to 2.25, P < 0.001), ductal subtype (OR 1.51, 95 per cent c.i. 1.17 to 1.97, P = 0.002) and grade 3 tumours (OR 2.20, 95 per cent c.i. 1.68 to 2.87, P < 0.001) were all associated with PgR negativity. In those receiving neoadjuvant chemotherapy (308 patients), pathological complete response rates were 10.1 per cent (25 of 247 patients) in patients with PgR+ disease versus 18.0 per cent in PgR- disease (11 of 61) (P = 0.050). PgR negativity independently predicted worse disease-free (hazard ratio (HR) 1.632, 95 per cent c.i. 1.209 to 2.204, P = 0.001) and overall survival (HR 1.774, 95 per cent c.i. 1.324 to 2.375, P < 0.001), as well as worse overall survival in ER+/HER2- disease (P = 0.004). CONCLUSIONS: In ER+ disease, PgR- tumours have more aggressive clinicopathological features and worse oncological outcomes. Neoadjuvant and adjuvant therapeutic strategies should be tailored according to PgR status.

Does Mode of Surgical Intervention Based on Oncotype DX Score Influence Disease Recurrence in Early Breast Cancer?

Introduction Routine utilization of multigene assays to inform operative decision-making in early breast cancer (EBC) treatment is yet to be established. In this pilot study, we sought to establish the potential benefits of surgical intervention in EBC based on recurrence risk quantification using the Oncotype DX (ODX) assay. Materials and Methods Consecutive ODX tests performed over a 9-year period from October 2007 to May 2016 were evaluated. Oncotype scores were classified into high (≥31), medium (18-30), or low-risk (0-17) groups. The primary outcome was breast cancer recurrence. Subgroup analysis offered assessment of the recurrence effect of mode of surgical intervention for patient groups as defined by the oncotype score. Results In total 361 patients underwent ODX testing. The mean age and follow-up were 55.25 (± 10.58) years and 38.59 (± 29.1) months, respectively. The majority of patients underwent wide local excision (86.7%) with 8.9 and 4.4% patients having a mastectomy or wide local excision with completion mastectomy, respectively. Fifty-one percent of patients fell into the low risk ODX category with a further 40.2 and 8.5% deemed to be of intermediate and high risk. Five patients (1.38%) had disease recurrence. Comparative analysis of operative groups in each oncotype group revealed no difference in recurrence scores in the low- ( p = 0.84) and high-risk groups ( p = 0.92) with a statistically significant difference identified in the intermediate risk group ( p = 0.002). Conclusion To date we have been unable to definitively identify a role for ODX in guiding surgical approach in EBC. There is, however, a need for larger studies to examine this hypothesis.

Five-year follow-up of patients treated with intra-dermal botulinum toxin for axillary hyperhidrosis.

BACKGROUND: Axillary hyperhidrosis is a common complaint affecting 5% of the general population. It can significantly impact quality of life (QOL) and may be extremely debilitating. Administration of intra-dermal botulinum toxin type-A (Botox) has been proven to be effective in managing axillary hyperhidrosis; however, to date, no long-term data has assessed its efficacy. AIM: We aim to assess long-term (> 5 years) QOL outcomes in this patient cohort. METHODS: In this single-centre series, all patients attending for axillary botox, with five or more years of follow-up, were prospectively included. QOL was assessed in all patients using the validated assessment tool, the modified Dermatology Life Quality Index (DLQI). Standard statistical methods were utilised with data reported as mean (± standard deviation). Subgroup analysis utilising previously published departmental data allowed for further assessment of change in QOL over time. RESULTS: A total of 75 patients (83% female) met the inclusion criteria with 67% completing the DLQI assessment. Follow-up ranged from 5 to 10 years with a mean age of 37.6 years (± 8.82). The mean number of treatments over the study period was 12 (± 3.1). Mean overall post-treatment DLQI score was 1.6 (± 2.01). This represented a significant improvement in patient QOL (p = < 0.0001) associated with long-term botox application. This statistical significance was identified consistently across all components of the DLQI tool. CONCLUSION: These data suggest that the established early QOL benefits associated with intra-dermal botox administration for AH are sustained in the long term. This benefit was seen across all subsets of the DLQI tool.