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Background Oncotype DX testing has reduced the use of adjuvant chemotherapy in node-negative early breast cancer but less is known about its impact in node positive patients. Aim This study aimed to investigate the impact of Oncotype DX gene assay testing on the decision to offer adjuvant chemotherapy in oestrogen positive, human epidermal growth factor receptor 2 negative, 1-3 lymph node positive patients. Methods Retrospective review of all node positive patients who underwent Oncotype DX testing at a single centre. Clinicopathological data, as well as estimated survival benefit data (from the PREDICT tool), was evaluated by a multidisciplinary group of surgeons and oncologists. Treatment decisions based on clinicopathological data were compared to recurrence scores (RS). A cut off RS > 30 was used to offer adjuvant chemotherapy. Results The 69 patients were identified, of which 9 (13%) had an RS > 30 and assigned a high-genomic risk of recurrence. The 32 patients (46.4%) were offered adjuvant chemotherapy. Overall based on the use of the RS, the decision to offer adjuvant chemotherapy changed in 36% of patients, and ultimately 24 patients (34.7%) would have been spared chemotherapy. Conclusion Using clinicopathological data alone to make decisions regarding adjuvant chemotherapy in node positive breast cancer leads to overtreatment. Additional information on tumour biology as assessed by the Oncotype DX RS helps to select those patients who will benefit from adjuvant chemotherapy and spare patients from unnecessary chemotherapy.

Background: oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. Methods: all available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki67 2wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. Findings: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki67 2wk (p2wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. Interpretation: our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse. Funding: Cancer Research UK (CRUK/07/015).

Primary hyperparathyroidism is the third most common endocrine disorder in the western world with an estimated prevalence of 1-4 per 1000.The only curative treatment is surgical resection. Minimally invasive surgical techniques are preferred over bilateral neck exploration due to reduced risk of surgical complications (1.2% vs 3%) and seven-fold shorter hospital stay with cost reduction of up to 50% (1); however this requires accurate preoperative localisation. Various imaging modalities evolved over time to identify pathological parathyroid glands pre-operatively. Imaging modality which is non-invasive, accurate and has minimal radiation exposure should be preferred as a first line option. Planar Technetium-99m Sestamibi scintigraphy coupled with Ultrasonography (MIBI/USS) has conventionally been used as the localisation study of choice. Single Photon Emission Computed Tomography (SPECT)/CT has been introduced recently and adopted by our centre as a first line investigation. The aim of the current study was to compare the accuracy of MIBI/USS versus SPECT/CT in localising pathological parathyroid glands preoperatively and assess the influence of imaging modality on surgical outcomes. A total of 135 patients with confirmed primary hyperparathyroidism were studied retrospectively in a tertiary centre over 24 months period. 61 patients underwent MIBI/USS and 74 had SPECT/CT as first line imaging. 82% of patients were female with mean age of 67 years. Preoperatively Sestamibi -SPECT/CT identified the laterality of the adenoma in 78.4% of cases, compared to 49.2% in MIBI/USS (p

An institutional review board-approved, multicenter clinical trial was designed to determine the efficacy and outcome of percutaneous laser ablation (PLA) in the treatment of invasive ductal breast carcinoma (IDC). Post-ablation magnetic resonance imaging (MRI) was compared with surgical pathology in evaluation of residual post-ablation IDC and ductal carcinoma in situ.Patients with a single focus of IDC 20 mm or smaller by pre-ablation MRI were treated with PLA. The patients underwent a 28-day post-ablation MRI, followed by surgical resection. Cell viability criteria were applied to pre- and post-ablation pathology specimens, which evaluated hematoxylin-eosin (HE), cytokeratin (CK) 8/18, estrogen receptor, and Ki67 staining patterns.In this study, 61 patients were reported as the intention-to-treat cohort for determination of PLA efficacy. Of these 61 patients, 51 (84%) had complete tumor ablation confirmed by pathology analysis. One subject's MRI imaging was not performed per protocol, which left 60 subjects evaluable for MRI pathology correlation. Five patients (8.3%) had residual IDC shown by both MRI and pathology. Post-ablation discordance was noted between MRI and pathology, with four patients (6.7%) false-positive and four patients (6.7%) false-negative. The negative predictive value (NPV) of MRI for all the patients was 92.2% (95% confidence interval [CI], 71.9-91.9%). Of the 47 patients (97.9%) with tumors 15 mm or smaller, 46 were completely ablated, with an MRI NPV of 97.7% (95% CI, 86.2-99.9%).Percutaneous laser ablation is a potential alternative to surgery for treatment of early-stage IDC. Strong correlations exist between post-ablation MRI and pathologic alterations in CK8/18, ER, and Ki67 staining.

The optimal management of a young patient with a BRCA1 gene mutation is a difficult problem faced by breast cancer clinicians of all disciplines on a regular basis. Management must be decided on an individual basis, taking into account both the needs of the individual patient and current evidence. Recent debate has centred on the optimal surveillance strategy for patients with BRCA1mutations. This has tended to overshadow arguments in favour of risk-reducing strategies. This article provides an overview of the current evidence surrounding BRCA1 mutations; the risks they confer and optimal management strategies. The aim is to enable breast cancer clinicians to counsel patients appropriately and to stimulate debate within the multidisciplinary team.

Background The aim of this review is to introduce the topic of next-generation DNA sequencing, a new technology that is being introduced into clinical practice, and to explain the potential impact for breast cancer surgeons and the wider breast cancer multidisciplinary team. Methods The PubMed database was used to identify relevant studies relating to breast cancer genetics. This evidence was then used to provide context and background information to demonstrate how next-generation sequencing (NGS) might change breast cancer practice. Results With NGS, breast cancer clinicians will know whether their patients carry high-risk mutations in genes, such as BRCA1 or BRCA2, before the start of treatment. This could alter treatment decisions; for instance, more women might opt for mastectomy instead of breast-conserving surgery, or for bilateral rather than unilateral surgery. Conclusion The introduction of NGS will have a significant impact on breast cancer services in the near future. Speed of testing will improve in regions of the world where NGS is adopted in place of conventional sequencing, and, as costs decrease, genetic testing will also become accessible and realistic in less well funded health economies. This will create opportunities to improve patient treatment and challenges for the breast cancer multidisciplinary team.

Risk-reducing mastectomy (RRM) confers 90-95% decreased risk of breast cancer, and may reduce mortality, especially in high-risk groups such as BRCA carriers. Risk of occult disease in RRM specimen is ~5%. This demands axillary staging: sentinel lymph node (SLN) biopsy is no longer possible, axillary clearance confers significant risks and may prove negative. Contemporaneous SLN biopsy allows axillary staging with minimal further dissection. Women undergoing RRM and SLN biopsy between June 2005 and July 2010 were reviewed retrospectively from our prospectively maintained database of 1,522 SLN procedures in 1,498 patients. SLN(s) localized using routine tracer methods. SLNs and mastectomy specimens underwent routine histologic examination. Eighty-three RRMs with SLN biopsy were performed in 71 patients (12 bilateral). Indications for RRM: contralateral invasive (55), in situ (5) disease, BRCA 1/2 mutation (12), and strong family history (10). Mean number of SLNs: 1.35. Occult disease was detected in four cases (4.8%), with one case of occult invasive lobular carcinoma (1.2%). Remaining occult disease was lobular in situ neoplasia (LISN). SLNs were negative in all cases. Our findings are comparable to those in the literature: 4.8% rate of occult disease overall, 1.2% invasive. The significant risk with SLN biopsy is lymphoedema, quoted around 7%. We have had no reports of symptomatic lymphoedema in patients undergoing RRM and SLN biopsy. We propose that SLN at the time of mastectomy requires only limited further dissection, and confers minimal risk compared with secondary axillary surgery.

Recent clinical reports have suggested that continuous delivery of oxygenated warm blood cardioplegia through the coronary veins (retrograde cardioplegia) produces good myocardial preservation during aortic cross-clamping. No data exist, however, about actual myocardial metabolism/homeostasis during retrograde warm blood cardioplegia. We studied 100 consecutive patients undergoing coronary artery bypass grafting, aortic valve replacement, or both who received retrograde continuous warm blood cardioplegia (4:1 dilution) during aortic cross-clamping for 54 to 174 minutes. We measured pH, oxygen tension, carbon dioxide tension, HCO 3 , base excess, and oxygen content of the inflow cardioplegia and the blood egressing from coronary arteries during each arteriotomy for bypass grafting (arteries act as postcapillary veins with retrograde cardioplegia) or the left and right coronary orifices during aortic valve replacement. We also measured these variables from the coronary sinus effluent 1 minute after release of the aortic cross-clamp. Retrograde cardioplegia flow ranged from 50 to 250 mL/min (mean flow, 150 mL/min). All patients were maintained at normothermia during bypass. A total of 460 samples were analyzed (4.6 per patient). Neither the duration of aortic cross-clamping nor the artery sampled affected myocardial blood gases. The pH dropped from 7.41 ± 0.05 for the inflow cardioplegia to 7.32 ± 0.1 when sampled from coronary arteries, and the oxygen tension fell from 181 ± 25 to 28 ± 5 mm Hg, respectively. Carbon dioxide tension rose from 31.0 ± 4.1 to 41.4 ± 9.8 mm Hg. Coronary sinus blood gases 1 minute after cross-clamp removal showed no acidosis or oxygen debt. These results indicate that (1) myocardial homeostasis is preserved by retrograde continuous warm blood cardioplegia during normothermic aortic cross-clamping for up to 3 hours in humans; (2) normal myocardial metabolism and oxygen uptake can be maintained solely by retrograde cardioplegia in the arrested heart, eliminating oxygen debt and ischemia; and (3) unlike experimental models, the arrested human heart is very active metabolically. Further application of this new clinical technique appears warranted, provided appropriate monitoring is used.

Risk-reducing mastectomy (RRM) confers 90-95% decreased risk of breast cancer, and may reduce mortality, especially in high-risk groups such as BRCA carriers. Risk of occult disease in RRM specimen is ~5%. This demands axillary staging: sentinel lymph node (SLN) biopsy is no longer possible, axillary clearance confers significant risks and may prove negative. Contemporaneous SLN biopsy allows axillary staging with minimal further dissection. Women undergoing RRM and SLN biopsy between June 2005 and July 2010 were reviewed retrospectively from our prospectively maintained database of 1,522 SLN procedures in 1,498 patients. SLN(s) localized using routine tracer methods. SLNs and mastectomy specimens underwent routine histologic examination. Eighty-three RRMs with SLN biopsy were performed in 71 patients (12 bilateral). Indications for RRM: contralateral invasive (55), in situ (5) disease, BRCA 1/2 mutation (12), and strong family history (10). Mean number of SLNs: 1.35. Occult disease was detected in four cases (4.8%), with one case of occult invasive lobular carcinoma (1.2%). Remaining occult disease was lobular in situ neoplasia (LISN). SLNs were negative in all cases. Our findings are comparable to those in the literature: 4.8% rate of occult disease overall, 1.2% invasive. The significant risk with SLN biopsy is lymphoedema, quoted around 7%. We have had no reports of symptomatic lymphoedema in patients undergoing RRM and SLN biopsy. We propose that SLN at the time of mastectomy requires only limited further dissection, and confers minimal risk compared with secondary axillary surgery.