Clinicopathological and prognostic significance of programmed cell death ligand 1 expression in patients diagnosed with breast cancer: meta-analysis.

BACKGROUND: Uncertainty exists regarding the clinical relevance of programmed cell death ligand 1 (PD-L1) expression in breast cancer. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Observational studies that compared high versus low expression of PD-L1 on breast cancer cells were identified. Log hazard ratios (HRs) for disease-free and overall survival and their standard errors were calculated from Kaplan-Meier curves or Cox regression analyses, and pooled using the inverse-variance method. Dichotomous variables were pooled as odds ratios (ORs) using the Mantel-Haenszel method. RESULTS: Sixty-five studies with 19 870 patients were included; 14 404 patients were classified as having low and 4975 high PD-L1 expression. High PD-L1 was associated with achieving a pathological complete response following neoadjuvant chemotherapy (OR 3.30, 95 per cent confidence interval 1.19 to 9.16; P < 0.01; I2 = 85 per cent). Low PD-L1 expression was associated with human epidermal growth factor receptor 2 (OR 3.98, 1.81 to 8.75; P < 0.001; I2 = 96 per cent) and luminal (OR 14.93, 6.46 to 34.51; P < 0.001; I2 = 99 per cent) breast cancer subtypes. Those with low PD-L1 had favourable overall survival rates (HR 1.30, 1.05 to 1.61; P = 0.02; I2 = 85 per cent). CONCLUSION: Breast cancers with high PD-L1 expression are associated with aggressive clinicopathological and immunohistochemical characteristics and are more likely to achieve a pathological complete response following neoadjuvant chemotherapy. These breast cancers are, however, associated with worse overall survival outcomes.

Association of BMI with Clinicopathological Features of Papillary Thyroid Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer. The incidence of PTC is rising in tandem with an obesity epidemic. Associations have been demonstrated between increased body mass index (BMI) and worse oncological outcomes in a number of malignancies. However, research on this topic in PTC to date has been inconsistent, often due to limited data. This study aimed to measure the association between BMI and potentially adverse clinicopathological features of PTC. METHODS: A meta-analysis of studies reporting outcomes after surgical treatment of PTC was performed. PubMed, Embase and the Cochrane Library were searched systematically to identify studies which provided data on BMI and clinicopathologic features of PTC. Relevant data were extracted and synthesis performed using adjusted odds ratios where available and crude values when not. Data were analysed by inverse variance using random and fixed effects models. RESULTS: Data on 35,237 patients from 15 studies met the criteria for inclusion. Obesity was associated with larger tumour size (MD = 0.17 cm [0.05, 0.29]), increased rates of multifocality (OR = 1.41 [1.16, 1.70]), extrathyroidal extension (OR = 1.70 [1.39, 2.07]) and nodal spread (OR = 1.18 [1.07, 1.30]). Associations were more pronounced as BMI increased. There was no association between BMI and bilaterality, vascular invasion or metastatic spread. CONCLUSION: Increased BMI is significantly associated with multiple potentially adverse features of PTC. The effect on long-term oncological outcomes requires further evaluation.

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.

Breast infections - Microbiology and treatment in an era of antibiotic resistance.

INTRODUCTION: Primary breast abscesses occur in <1% of non-lactating women, rising to 11% in women with lactational mastitis. In patients undergoing breast cancer surgery, the inflammatory response to post-operative surgical site infection (SSI) has been implicated in recurrence. Anti-microbial resistance increasingly hampers treatment in each group. AIMS: Describe the demographic and predisposing characteristics of patients with primary breast abscesses and secondary infections, identify the microbial and antimicrobial patterns and formulate an evidence-based protocol for treating breast infections. METHODS: Retrospective cohort study of all breast infections (primary and post-operative) treated at UHL from 2014 to 2017. Data collected from microbiology databases and patient records was analysed using Minitab V18. RESULTS: 537 cultures from 108 patients were analysed. 47 (43.5%) had primary abscesses, 12 (11.1%) were lactational and 49 (45.4%) were post-operative SSI. For primary infections, the mean age was 41.9 (±12.2) and reinfection rate 33%. For SSIs the mean age was 51.8 (±14.52) and reinfection rate 11.8%. Overall, 29.3% were smokers, 6.4% diabetic and 2.9% pregnant. 60 (43%) patients required radiological drainage and 2 (1%) surgical drainage. 57.5% had mixed growth. The most common isolate was Staphylococcus aureus; cultured in 16.7% of primary abscesses and 24% of SSIs. 13 empiric antibiotic regimes were prescribed before 26.4% of patients changed to 12 different targeted regimes. CONCLUSION: Breast infections are frequently polymicrobial with a wide variety of organisms isolated, suggesting the need for broad spectrum coverage until culture results become available. Based on our local culture results, the addition of clindamycin to flucloxacillin would provide excellent empiric coverage for all categories of breast infection. An evidence-based treatment guideline is required and should be formulated in close collaboration with microbiology specialists.

Meta-analysis of the diagnostic accuracy of ultrasound-guided fine-needle aspiration and core needle biopsy in diagnosing axillary lymph node metastasis.

BACKGROUND: Axillary lymph node status remains a significant prognostic indicator in breast cancer. Here, the diagnostic accuracy of ultrasound-guided fine-needle aspiration (US-FNA) and ultrasound-guided core needle biopsy (US-CNB) in axillary staging was compared. METHODS: A comprehensive search was undertaken of all published studies comparing the diagnostic accuracy of US-CNB and US-FNA of axillary lymph nodes in breast cancer. Studies were included if raw data were available on the diagnostic performance of both US-FNA and US-CNB, and compared with final histology results. Relevant data were extracted from each study for systematic review. Meta-analysis was performed using a random-effects model. The pooled sensitivity and specificity of US-FNA and US-CNB were obtained using a bivariable model. Summary receiver operating characteristic (ROC) graphs were created to confirm diagnostic accuracy. RESULTS: Data on a total of 1353 patients from six studies met the inclusion criteria and were included in the final analysis. US-CNB was superior to US-FNA in diagnosing axillary nodal metastases: sensitivity 88 (95 per cent c.i. 84 to 91) versus 74 (70 to 78) per cent respectively. Both US-CNB and US-FNA had a high specificity of 100 per cent. Reported complication rates were significantly higher for US-CNB compared with US-FNA (7·1 versus 1·3 per cent; P < 0·001). Conversely, the requirement for repeat diagnostic procedures was significantly greater for US-FNA (4·0 versus 0·5 per cent; P < 0·001). CONCLUSION: US-CNB is a superior diagnostic technique to US-FNA for axillary staging in breast cancer.

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.

Prospective comparison of outcome after treatment for triple-negative and non-triple-negative breast cancer.

INTRODUCTION: Triple-negative breast cancers (TNBC) are associated with a poor prognosis owing to an aggressive phenotype. We aimed to carry out a prospective study comparing management strategies and response to therapy in TNBC and non-TNBC patients. METHODS: Data were obtained from a prospectively maintained database of patients treated for breast cancer. RESULTS: A total of 142 TNBC and 142 age-, stage- and NPI-matched non-TNBC patients were treated. The difference in overall survival between the 2 groups was statistically significant (77% of TNBC patients alive at a mean follow-up of 32 months, versus 92% of non-TNBC patients at a mean follow-up of 38 months, P = 0.0 Log rank test). This survival difference was found to be independent of NPI (P = 0.0 Log rank test). Locoregional recurrence rates were similar between TNBC patients who were treated with wide local excision versus mastectomy (P = 0.449 Log rank test). A significant difference in survival was noted between TNBC patients who responded differentially to neoadjuvant chemotherapy (P = 0.035 Log rank test). CONCLUSION: Patients with TNBC have adverse outcomes despite aggressive treatment. The development of effective targeted therapies is essential for this breast cancer subtype.

Adrenocortical carcinoma surgery-surgical extent and approach.

PURPOSE: Adequate tumour resection is the gold standard of care for adrenocortical carcinoma (ACC). However, the optimal surgical strategy remains debatable. In our opinion, the extent of surgery (adequate tumour resection) is the primary concern, rather than the surgical approach (laparoscopic or open). We propose that both surgical approaches have a role in the management of ACC provided the extent of resection is selected based on patient and tumour characteristics and accurate pre-operative investigations. METHODS: A review of 25 curative intent resections for ACC between 2002 and 2013 was done. Group A (16 patients-64 %) included all patients who underwent planned radical adrenalectomy without any other resection and group B (9 patients-36 %) included all patients who underwent a planned extensive resection based on pre-operative investigations. RESULTS: Of 471 adrenalectomies, 25 were performed for ACC with curative intent. Tumours were significantly larger in group B with mean size of 119.6 versus 62.4 mm in group A (p = 0.002). Tumours in group B also had higher WEISS scores (mean score 7 vs 5.2, p = 0.033) and almost always required multi-organ resection. The recurrence rate was 37.5 % (n = 6) for group A and 44.4 % for group B (n = 4), p = 1.00. Poor prognosis was associated with significantly higher WEISS scores (p = 0.016) and a trend towards more advanced ENSAT disease stage (p = 0.06). Estimated overall survival was 74.17 months (group A 67.3 vs group B 70.1, p = 0.244). CONCLUSIONS: Accurate pre-operative staging is critical to select a tailored surgical strategy. Multi-organ resection remains the preferred approach for large and potentially invasive ACC. Some patients presenting with smaller ACC may benefit from a more extensive resection.

Postmastectomy radiotherapy: indications and implications.

BACKGROUND: Although breast conservation surgery, when combined with radiotherapy, has been shown to provide excellent locoregional control for breast cancer, approximately one third of women with breast cancer require mastectomy. Many of these women are offered immediate reconstruction. Postmastectomy radiotherapy (PMRT) is indicated in some cases, but is associated with side-effects, including its impact on the reconstructed breast. OBJECTIVE: To review the pertinent issues surrounding PMRT, including patient selection for radiotherapy and the effect of radiotherapy on reconstructive decisions. METHODS: A literature review was performed using the Medline database. CONCLUSIONS: PMRT is indicated in patients who are deemed to have a high risk of loco-regional recurrence. Although PMRT is strongly recommended for patients with four or more positive lymphnodes, other indications for PMRT remain controversial. Immediate reconstruction post mastectomy has been shown to have favorable outcomes. However, PMRT may increase the need for revision surgery post immediate reconstruction. There are few randomized trials looking at these key issues, and the evidence is largely derived from observational retrospective studies. Patients should be carefully counseled before a decision is made to proceed with immediate reconstruction, where there is a high chance that PMRT may be indicated.

Changing practices in the surgical management of hyperparathyroidism - a 10-year review.

AIM: Parathyroid surgery has undergone a paradigm shift over the last decade, with a move from traditional bilateral neck exploration to minimally invasive parathyroidectomy (MIP), and increasing reliance on pre- and intra-operative localization of overactive glands. We aimed to assess changing surgical practices and their impact on the management of parathyroid disease in a tertiary referral centre in the West of Ireland. METHODS: A retrospective cohort analysis of those patients undergoing a surgical intervention for parathyroid disease in the period between 1999 and 2009 in our centre was carried out. Data was analysed using PASW (v18) software. RESULTS: 248 procedures were performed, increasing from an annual rate of 6 in 1999 to 45 in 2009. 129 procedures were completed by minimally invasive means, following the introduction of MIP in 2003. Single-gland disease accounted for 87% of cases (n = 216) with carcinomas in 2 patients (0.8%). Pre-operative localization had disappointing diagnostic value, with high false negative rates for both ultrasound (37.3%) and Sestamibi Scanning (35.81%). Intra-operative adjuncts were more helpful, with intra-operative Parathyroid hormone monitoring facilitating curative resection of adenomas in 94.03% at 10 min. Median length of post-operative stay has significantly decreased from 6 days in 1999 to 1 night only in 2009 (p < 0.01, ANOVA). Those patients undergoing MIP had shorter stay than the open group (1.71 days -v-4.73, p = 0.003,t-test). CONCLUSION: The practice in our centre has shifted to a less invasive approach. Increased utilisation of intra-operative adjuncts has facilitated this change, and resulted in favourable changes in length of stay, extent of dissection, and number of patients treated.

Successful introduction of ring-fenced inpatient surgical beds in a general hospital setting.

This study aimed to assess the impact of ring-fenced inpatient general surgical beds on day of surgery (DOS) admission, duration of elective inpatient stay (DEIS), and cancellation rates over a 6 month period. In June 2010 17 of 60 surgical inpatient beds were decommissioned. The remainder (43) were ring-fenced for general surgery patients only. Comparative analysis examining admission rates, cancellation rates, and theatre activity was performed between a reference period (January-June 2010) and the study period (July-December 2010). Complexity of all operations was graded according to an index schedule of procedures. There was no difference between the reference and study periods in volumes of elective admissions (472 [53.03%] vs. 418 [4797%]) and emergency admissions (928 [50.03%] vs. 927 [49.97%]). DOS admissions increased 5-fold during the study period (38 [8.1%] vs. 190 [45.5%], P < 0.001). Average duration of elective inpatient stay reduced from 4.3 days to 3.06 days in the study period (P < 0.001). No difference was observed in volume of operations performed at all levels of complexity. There were 78 (58.2%) cancellations during the reference period and 56 (41.8%) during the study period with patient non-attendance the most common cause for cancellation in both periods. Ring-fenced surgical beds facilitated higher DOS admission rates and shorter duration of elective inpatient stay, leading to more efficient use of hospital resources.

Paediatric surgery--a general hospital experience.

Plans to centralise paediatric surgery in Ireland have potentially significant implications for service provision and surgical training. study assesses the workload of paediatric surgery in a district hospital over a five-year period. Paediatric surgical admissions and procedures at Mayo General Hospital from January 2006 - December 2010 were reviewed. Data was obtained from the Hospital inpatient enquiry (HIPE) systems and theatre logbooks. 4,255 surgical procedures were performed in 3981 paediatric patients, accounting for 7.4% of the total surgical workload. 2,578 (65%) of cases were elective and 1403 (35%) of paediatric surgery was performed in the emergency setting; paediatric appendicectomy was the most commonly performed procedure (n = 554) with a complication rate of 2.5%. There were no paediatric surgery related mortalities. Paediatric surgery represents a significant part of the surgical workload. There is a continued need for general paediatric surgical provision in this regional setting, supported by access to specialist centres for complicated paediatric surgery.

Management of the acute appendix mass: a survey of surgical practice.

Management of the appendix mass is controversial with no consensus in the literature. Traditionally, the approach has been conservative followed by interval appendicectomy. A survey was distributed to 117 surgeons (100 consultants and 17 final year specialist registrars) to determine how the appendix mass is currently treated in Ireland. In total, 70 surgeons responded. 51 (73%) adopt a conservative approach initially. 48 (68%) favoured interval appendicectomy at six weeks after a period of successful conservative management. 34 (49%) gave risk of recurrence as the reason for performing interval appendicectomy and 16 (22%) would perform interval appendicectomy in order to obtain histological analysis to outrule caecal or appendiceal neoplasm. 44 (63%) opted for a laparoscopic rather than an open approach for interval appendicectomy. No consensus exists in Ireland for management of the appendix mass presenting acutely. The present series demonstrates a trend towards conservative approach initially followed by interval appendicectomy.

The accuracy of breast MRI radiomic methodologies in predicting pathological complete response to neoadjuvant chemotherapy: A systematic review and network meta-analysis.

BACKGROUND: Achieving pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) improves survival outcomes for breast cancer patients. Currently, conventional histopathological biomarkers predicting such responses are inconsistent. Studies investigating radiomic texture analysis from breast magnetic resonance imaging (MRI) to predict pCR have varied radiomic protocols introducing heterogeneity between results. Thus, the efficacy of radiomic profiles compared to conventional strategies to predict pCR are inconclusive. PURPOSE: Comparing the predictive accuracy of different breast MRI radiomic protocols to identify the optimal strategy in predicting pCR to NAC. MATERIAL AND METHODS: A systematic review and network meta-analysis was performed according to PRISMA guidelines. Four databases were searched up to October 4th, 2021. Nine predictive strategies were compared, including conventional biomarker parameters, MRI radiomic analysis conducted before, during, or after NAC, combination strategies and nomographic methodology. RESULTS: 14 studies included radiomic data from 2,722 breast cancers, of which 994 were used in validation cohorts. All MRI derived radiomic features improved predictive accuracy when compared to biomarkers, except for pre-NAC MRI radiomics (odds ratio [OR]: 0.00; 95 % CI: -0.07-0.08). During-NAC and post-NAC MRI improved predictive accuracy compared to Pre-NAC MRI (OR: 0.14, 95 % CI: 0.02-0.26) and (OR: 0.26, 95 % CI: 0.07-0.45) respectively. Combining multiple MRIs did not improve predictive performance compared to Mid- or Post-NAC MRIs individually. CONCLUSION: Radiomic analysis of breast MRIs improve identification of patients likely to achieve a pCR to NAC. Post-NAC MRI are the most accurate imaging method to extrapolate radiomic data to predict pCR.

NCCP breast cancer referral guidelines--are breast cancer patients prioritised?

Following centralisation of breast cancer services, the National Cancer Control Programme (NCCP) introduced referral guidelines indicating which patients require urgent, early and routine review. This study prospectively analysed referrals to a symptomatic breast unit over 3 months to measure Primary Care Physician (GP) uptake of the NCCP referral guidelines, compare triage patterns of GP and consultant breast surgeon and evaluate the efficacy of the guidelines at identifying patients with breast cancer. 1044 consecutive referrals were categorised according to NCCP guidelines. 637 (61%) were referred using the NCCP form. GP referrals correlated well with consultant breast surgeon for patients requiring urgent review (r = 0.71, p < 0.001; Pearson). Patients categorised as "urgent" were more likely to have a breast biopsy compared to those categorised as "routine" (p < 0.0001; Chi2). The overall cancer incidence was 34 (3.3%) and significantly higher in the "urgent" group at 10.5%. NCCP guidelines were 91% sensitive for triaging breast cancer patients into the correct (urgent) category. The NCCP guidelines are accurate and should be considered the gold-standard for referral to the symptomatic breast service. Consideration should be given to a GP-delivered service to patients outside the "urgent" category.

Combined breast conservation therapy versus mastectomy for BRCA mutation carriers - A systematic review and meta-analysis.

BACKGROUND: The non-inferiority of combined breast conservation surgery (BCS) and radiotherapy (breast conservation therapy or BCT) compared to mastectomy in sporadic breast cancer cases is well recognised. Uncertainty remains regarding optimal surgical practice in BRCA mutation carriers. AIMS: To evaluate the oncological safety of combined BCT versus mastectomy in BRCA mutation carriers following breast cancer diagnosis. METHODS: A systematic review was performed as per PRISMA and MOOSE guidelines. Observational studies comparing BCS and mastectomy in BRCA carriers were identified. Dichotomous variables were pooled as odds ratios (OR) using the Mantel-Haenszel method. Log hazard ratios (lnHR) for locoregional recurrence (LRR), contralateral breast cancer, disease-free and overall survival and their standard errors were calculated from Kaplan-Meier or cox-regression analyses and pooled using the inverse variance method. RESULTS: Twenty three studies of 3807 patients met inclusion criteria; 2200 (57.7%) were BRCA1 and 1212 (31.8%) were BRCA2 carriers. Median age at diagnosis was 41 years with 96 months follow up. BCS was performed on 2157 (56.7%) while 1408 (41.5%) underwent mastectomy. An increased risk of LRR was observed in patients treated with BCS (HR:4.54, 95% Confidence Interval: 2.77-7.42, P < 0.001, heterogeneity (I2) = 0%). However, the risks of contralateral breast cancer (HR:1.51, 95%CI: 0.44-5.11, P = 0.510, I2 = 80%), disease recurrence (HR:1.16, 95%CI: 0.78-1.72, P = 0.470, I2 = 44%), disease-specific recurrence (HR:1.58, 95%CI: 0.79-3.15, P = 0.200, I2 = 38%) and death (HR:1.10, 95%CI: 0.72-1.69, P = 0.660, I2 = 38%) were equivalent for combined BCT and mastectomy. CONCLUSIONS: Survival outcomes following combined BCT is comparable to mastectomy in BRCA carriers. However, the risk of LRR is increased. Patient counselling should be tailored to incorporate these findings.

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.

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.