Abstract Introduction In recognition of the advances and evidence based changes in clinical practice that have occurred in recent years and taking into account the knowledge and experience ...accumulated through the voluntary breast unit certification programme, Eusoma has produced this up-dated and revised guidelines on the requirements of a Specialist Breast Centre (BC). Methods The content of these guidelines is based on evidence from the recent relevant peer reviewed literature and the consensus of a multidisciplinary team of European experts. The guidelines define the requirements for each breast service and for the specialists who work in specialist Breast Centres. Results The guidelines identify the minimum requirements needed to set up a BC, these being an integrated Breast Centre, dealing with a sufficient number of cases to allow effective working and continuing expertise, dedicated specialists working with a multidisciplinary approach, providing all services throughout the patients pathway and data collection and audit. It is essential that the BC also guarantees the continuity of care for patients with advanced (metastatic) disease offering treatments according to multidisciplinary competencies and a high quality palliative care service. The BC must ensure that comprehensive support and expertise may be needed, not only through the core BC team, but also ensure that all other medical and paramedical expertise that may be necessary depending on the individual case are freely available, referring the patient to the specific care provider depending on the problem. Conclusions Applying minimum requirements and quality indicators is essential to improve organisation, performance and outcome in breast care. Efficacy and compliance have to be constantly monitored to evaluate the quality of patient care and to allow appropriate corrective actions leading to improvements in patient care.
Abstract Background Blue dye with or without isotope has been widely used to identify the sentinel lymph node(s) in breast cancer. Patent blue V is used in the UK while its isomer isosulfan blue is ...used in the US. The allergic potential of isosulfan blue is well documented (1.4% adverse reactions) but that of patent blue V is less clearly defined. Methods In this paper we review the adverse reactions of patent blue V in 7,917 patients who participated in the NEW START training programme and the ALMANAC trial. All patients underwent sentinel lymph node biopsy for breast carcinoma using patent blue V in combination with99m Tc-albumin colloid. Results In total, 72 of 7,917 (0.9%) patients experienced adverse reactions : non-allergic reactions were observed in 4 (0.05%) patients, 23 (0.3%) patients had minor grade I allergic skin reactions (urticaria, blue hives, pruritis, or generalised rash) and 16 (0.2%) had grade II reactions (transient hypotension/bronchospasm/laryngospasm). Severe Grade III reactions (severe hypotension requiring vasopressor support and/or change/abandoning of planned procedure and/or HDU/ITU admission) were noted in 5 (0.06%) patients. The type of adverse reaction was not specified in 24 (0.3%) patients. No mortality was recorded. Conclusion The allergic potential of patent blue V dye compares favourably with isosulfan blue however both the surgeon and anaesthetist need to be alert to the risk of allergic reactions.
The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary ...care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006–2015.
Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006–2015.
On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor–negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015.
The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.
•The time trends of quality indicators in EUSOMA-certified breast centres over the decade 2006–2015 are evaluated.•The EUSOMA model of audit and monitoring QIs functions well in different European health systems.•Audit and measuring quality indicators result in better performance.
In 2010, EUSOMA published a position paper, describing a set of benchmark quality indicators (QIs) that could be adopted by breast centres to allow standardised auditing and quality assurance and to ...establish an agreed minimum standard of care. Towards the end of 2014, EUSOMA decided to update the paper on QIs to consider and incorporate new scientific knowledge in the field. Several new QIs have been included to address the need for improved follow-up care of patients following primary treatments. With regard to the management of elderly patients, considering the complexity, the expert group decided that, for some specific quality indicators, if centres fail to meet the minimum standard, older patients will be excluded from analysis, provided that reasons for non-adherence to the QI are specified in the clinical chart and are identified at the review of the clinical records. In this way, high standards are promoted, but centres are able to identify and account for the effect of non-standard treatment in the elderly. In the paper, there is no QI for outcome measurements, such as relapse rate or overall survival. However, it is hoped that this will be developed in time as the databases mature and user experience increases. All breast centres are required to record outcome data as accurately and comprehensively as possible to allow this to occur. In the paper, different initiatives undertaken at international and national level to audit quality of care through a set of QIs have been mentioned.
In many patients, the sentinel lymph node (SLN) is the sole site of regional nodal metastasis. This subgroup of patients would not be expected to benefit from completion axillary lymph node ...dissection (CALND). This study evaluated the factors that may determine the likelihood of additional positive nodes in the axilla in the presence of sentinel node metastasis. A total of 618 breast cancer patients underwent SLN biopsy based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 99mTc-nanocolloid and Patent Blue V injected peritumourally. This was followed by standard axillary node clearance at the same operation. Of the 201 patients with a positive SLN, 105 (52%) patients had no further positive nodes in the axilla, 96 (48%) patients had additional metastasis in non-sentinel lymph nodes (NSLN) upon CALND. In patients with a positive SLN, increasing tumour size and tumour grade significantly increased the frequency of additional positive nodes on univariate analysis. The number of SLNs removed and the number of negative SLNs were significant negative predictors. Increasing tumour burden in the sentinel nodes (determined by the number of positive SLNs) was significantly associated with increasing likelihood of positive NSLNs. Multivariate analysis revealed that the rest of the axilla is more likely to be positive if there are more positive than negative SLNs removed and more likely to be negative otherwise. A group of cases from one centre (Cardiff) were subjected to further detailed analysis. Tumour burden in the positive SLN was assessed by measuring the size of metastasis, percentage replacement of the SLN by tumour and by documenting extracapsular extension (ECE) around the SLN. Of the 64 patients with a positive SLN, 34 (53%) patients had no further positive nodes in the axilla, 30 patients (47%) had additional metastasis in NSLNs upon CALND. Increasing tumour burden in the SLN was associated with additional positive nodes in the axilla. Multivariate analysis revealed that size of the SLN metastasis is the most important predictor of involvement of only the SLN. Overall, in patients with a positive SLN, the difference in the number of positive and negative SLNs removed and size of the metastasis in the SLN, all predicted the frequency of additional positive nodes.
Background: Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from randomized trials on morbidity and ...mortality outcomes. We conducted a multicenter randomized trial to compare quality-of-life outcomes between patients with clinically node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received standard axillary treatment. Methods: The primary outcome measures were arm and shoulder morbidity and quality of life. From November 1999 to October 2003, 1031 patients were randomly assigned to undergo sentinel lymph node biopsy (n = 515) or standard axillary surgery (n = 516). Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy (depending on the protocol at the treating institution). Intention-to-treat analyses of data at 1, 3, 6, and 12 months after surgery are presented. All statistical tests were two-sided. Results: The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the standard axillary treatment group at 12 months were 0.37 (95% confidence interval CI = 0.23 to 0.60; absolute rates: 5% versus 13%) and 0.37 (95% CI = 0.27 to 0.50; absolute rates: 11% versus 31%), respectively. Drain usage, length of hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group (all P<.001), and axillary operative time was reduced (P = .055). Overall patient-recorded quality of life and arm functioning scores were statistically significantly better in the sentinel lymph node biopsy group throughout (all P≤.003). These benefits were seen with no increase in anxiety levels in the sentinel lymph node biopsy group (P>.05). Conclusion: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.
Background
New Start, a structured, validated, multidisciplinary training programme in sentinel lymph node biopsy (SLNB), was established to allow the introduction and rapid transfer of appropriate ...knowledge and technical skills to ensure safe and competent practice across the UK.
Methods
Multidisciplinary teams attended a theory/skills laboratory course, following which they performed 30 consecutive SLNBs, either concurrently with their standard axillary staging procedure (training model A) or as stand‐alone SLNB (training model B). SLNB was performed according to a standard protocol using the combined technique of isotope (99mTc‐labelled albumin colloid) and blue dye. An accredited New Start trainer mentored the first five procedures in the participant's hospital, or all 30 if stand‐alone. Validation standards for model A and B were a localization rate of at least 90 per cent. In addition, for model A only, in which a minimum of ten patients were required to be node‐positive, a false‐negative rate (FNR) of 10 per cent or less was required.
Results
From October 2004 to December 2008, 210 SLNB‐naive surgeons, in 103 centres, performed 6685 SLNB procedures. The overall sentinel lymph node (SLN) localization rate was 98·9 (95 per cent confidence interval 98·6 to 99·1) per cent (6610 of 6685) and the FNR 9·1 (7·9 to 10·5) per cent (160 of 1757). The FNR was related to nodal yield, ranging from 14·8 per cent for one node and declining to 9·7, 6·6, 4·7 and 4·1 per cent for two, three, four and more than four SLNs respectively. No learning curve was identified for localization or FNR.
Conclusion
The programme successfully trained a wide range of UK breast teams to perform safe SLNB and suggested that a standard injection protocol and structured multidisciplinary training can abolish learning curves.
Good start
The tuberous sclerosis (TSC) genes
TSC1 and
TSC2 encode the protein products hamartin and tuberin, respectively, and are putative tumour suppressor genes. Germ-line mutation of either TSC gene leads ...to the development of the heritable disorder TSC. This disorder is characterized by the development of hamartomas in many organs and is associated with the proliferative lung disease, lymphangioleiomyomatosis, the brain tumour giant cell astrocytoma and occasionally with renal cell carcinoma. However, the TSC genes have not been studied in breast cancer. The current study investigated the expression of the
TSC gene products and the potential mechanisms of their aberrancy in human breast cancer cells and tissues.
Using immunohistochemical analysis, both hamartin and tuberin were found to be strongly stained in normal mammary epithelial cells and weakly in stromal cells. In invasive tumour tissues, however, the staining of both proteins were to be markedly reduced (
P
<
0.01). At message level, although normal and tumour tissues expressed both
TSC products, the transcript levels of tuberin was significantly lower in tumour tissues compared with normal tissues (
P
<
0.05). There was no statistical difference between node negative and node positive tumours with both hamartin and tuberin. Tumours from patients who developed recurrence and died from breast cancer had significantly low levels of tuberin compared with those who remained disease free (
P
=
0.03 and 0.05, respectively). Likewise, hamartin levels were significantly lower in patients with metastasis, recurrence and mortality, when compared with those remained disease free (
P
=
0.001, 0.041 and 0.003, respectively). Using methylation specific PCR, the
TSC1 promoter was found to be heavily methylated in ZR751, MDA MB 435, and BT549, but not in MCF-7 which expressed highly level of hamartin.
TSC1 promoter methylation was also seen in most breast tumours, but only in a limited number of normal tissues. The methylation of
TSC2 promoter appears to be less frequent. MDA MB 468, MDA MB 483, MDA MB 435S and weakly MDA MB 435 were found to have methylated
TSC2 promoter. In breast tissues, however, a very small number of samples were found to have methylation of the
TSC2 promoter.
TSC1 genes are aberrantly expressed in human breast cancer cell lines and breast tumour tissues and their promoters are seen to be methylated in breast tumour tissues. The expression of
TSC1 is associated with an unfavourable clinical outcome in patients with breast cancer.
Interleukin-7 (IL-7), a haematopoietic growth factor, is known to induce the differentiation and proliferation of some haematological malignancies including certain types of leukaemias and lymphomas. ...However, little is known about its role in solid tumours, including breast cancer. In this study, the expression level of IL-7, IL-7 receptor (IL-7R) and their downstream signalling molecules, including the Janus kinases (Jak-1 and Jak-3), phosphoinositide 3-kinase (PI3-K) and signal transducers and activators of transcription (Stat-5) were analysed using the reverse transcriptase-polymerase chain reaction (RT-PCR), real-time quantitative PCR and immunohistochemistry in a cohort of patients with breast cancer. The results were analysed in relation to tumour grade, TNM stage, patients' prognosis (using the Nottingham Prognostic Index (NPI)) and survival. The levels of expression of IL-7, IL-7R, Jak-1, Jak-3, PI3-K and Stat-5 were significantly higher in the most aggressive tumours. With the exception of Stat-5 expression, the transcript copies of IL-7 and all other signalling molecules were higher in patients with the worst prognoses (NPI3) and in patients who died from breast cancer after 72 months of follow-up. This aberrant expression of IL-7 and its signalling intermediates in invasive breast cancers could have significant diagnostic and prognostic implications. Measuring these molecules in breast cancer tissues may provide, for the first time, important molecular indicators of tumour differentiation, aggressiveness, nodal status, prognosis and patient survival.
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