Photodynamic therapy: Inception to application in breast cancer.

Photodynamic therapy (PDT) is already being used in the treatment of many cancers. This review examines its components and the new developments in our understanding of its immunological effects as well as pre-clinical and clinical studies, which have investigated its potential use in the treatment of breast cancer.

The use of onestep nucleic acid amplification (OSNA) and tumour related factors in the treatment of axillary breast cancer: A predictive model.

AIMS: We aimed to determine the effectiveness of CK19 mRNA copy number and tumour related factors in predicting non-sentinel axillary nodal involvement, in order to facilitate the formulation of local treatment guidelines for axillary clearance (ANC) following intra-operative analysis of the sentinel node biopsy (SNB) using one-step nucleic acid amplification (OSNA). METHODS: Patients due to have (SNB) at our institution for breast cancer as well as patients with high grade ductal carcinoma in situ with pre-operative negative assessment of the axilla were included. Alternate slices of each node were sent for assessment by either OSNA or histopathology. Immediate ANC was performed if OSNA was positive. The CK19 mRNA nodal copy number, the total tumour load (TTL) measured by summation of mRNA copy numbers of all positive nodes, the nodal status at ANC and tumour characteristics for each patient were recorded. A model of risk probability was constructed using TTL and tumour related factors. RESULTS: 664 nodes were analysed from 425 patients who had SNB performed between 2011 and 2014. ANC was performed on 105 of these patients. The concordance between OSNA and histology was 91.4% and negative predictive value (NPV) was 97%. TTL (p = 0.003) and LVI (p = 0.04) were identified as risk factors for non-sentinel nodal involvement. The risk probability model identified all patients with pN2 disease for ANC. CONCLUSION: In the future a decision to perform ANC will be based on a risk stratification model based on TTL and tumour related factors.

Contribution of perioperative imaging to radioguided surgery.

Radioguided surgery has been investigated and applied to almost any neoplastic disease that is surgically treated. The impact of radioguided surgery on the surgical management of cancer patients includes relevant and real-time information to the surgeon regarding the location and extent of the disease, as well as regarding the assessment of surgical resection margins. Despite the fact that sentinel lymph node biopsy has been worldwide accepted as a highly accurate staging method for various solid cancers (among which breast cancer and cutaneous melanoma), some potential intraoperative drawbacks still remain. This article provides an update on currently available perioperative techniques regarding the use of radiotracers for radioguided surgery and sentinel lymph node mapping and biopsy, in particular in combination with vital dyes or other agents. The integration of computer technology and data processing makes it possible to integrate anatomic and functional images together with 3D rendering systems. This facilitates the targeted-tissue perioperative localization, especially in anatomically complex areas. Furthermore, we provide an update on advances in the integration of intraoperative imaging devices as well as optical tracers for the surgical management of patients. Evidence is emerging that these devices, together with new potential tracers, may improve intraoperative identification of sentinel nodes and/or tumors. A detailed presentation on a portable gamma camera in breast cancer patients, and the application of perioperative imaging devices in gynaecological cancers are included. Other important procedures, such as ROLL and RSL for occult lesion excision in the breast and other organs, are extensively discussed.

Concordance between peri-areolar blue dye and peri-incisional radiotracer injections for sentinel node mapping in patients with a history of primary breast cancer excisonal biopsy.

BACKGROUND: We evaluated the concordance between peri-areolar blue dye and peri-incisional radiotracer injections for axillary sentinel node mapping of patients with the history of previous breast lesion excisional biopsy. METHODS: 80 patients with the history of previous excisional biopsy of the breast lesions were included. All patients received two injections of 99mTc-antimony sulfide colloid in both ends of incision line in an intradermal fashion. 2 mL patient blue V dye was injection to all patients in the peri-areolar area of the index quadrant after induction of anesthesia. All blue or hot nodes were harvested as sentinel lymph nodes. RESULTS: At least one sentinel node could be detected during surgery in 79 patients. In total 94 sentinel nodes were detected. All detected sentinel nodes were hot. In three patients sentinel nodes were detected by gamma probe but not blue dye. The tumor location in all of these patients was in the upper lateral quadrant and the incision line was extended into the axillary tail of the breast in all of them. 91 out of 94 sentinel nodes were stained blue, which amounts to 95.8% concordance between blue dye and radiotracer on a per node analysis. CONCLUSIONS: Single peri-areolar injection in the index quadrant would suffice for sentinel node mapping of patients with history of excisional biopsy. Care should be taken in patients with large excisional biopsy in the extreme proximity to axilla.

Reproducibilidad de la linfogammagrafía antes y después de la biopsia excisional de las lesiones primarias de mama: estudio utilizando la inyección periareolar superficial del radiotrazador / Reproducibility of lymphoscintigraphy before and after excisional biopsy of primary breast lesions: A study using superficial peri-areolar injection of the radiotracer

Objetivo. Una cuestión de gran controversia en la biopsia del ganglio centinela de la mama es la aplicabilidad del estudio del ganglio centinela en pacientes con historia previa de biopsia excisional de las lesiones de la mama. En el presente estudio, evaluamos la reproducibilidad de la linfogammagrafía antes y después de la biopsia excisional de las lesiones primarias de mama utilizando la inyección periareolar superficial del radiotrazador. Material y métodos. Se incluyó en el estudio a 18 pacientes programadas para biopsia excisional de lesiones de mama. A las pacientes se les administró una inyección intradérmica del radiotrazador en el área periareolar del cuadrante con tumor, con 1 o 2h antes de la cirugía. La imagen se obtuvo el día posterior a la operación. Inmediatamente tras la primera imagen, a las pacientes se les administró otra inyección del radiotrazador con la misma técnica, dosis y localización. Se realizaron inmediatamente otras series de imágenes de linfogammagrafía, y a las 4h después de la segunda inyección. Se compararon las 2 series de imágenes de linfogammagrafía. Resultados. En 2 pacientes no se pudo identificar el ganglio centinela en ninguna de las series de imágenes. En las 16 pacientes restantes se detectó un ganglio centinela en ambas series de imágenes de linfogammagrafía. Los ganglios centinela de las segundas series de imágenes se detectaron en la misma localización que las primeras series de imágenes, con un contaje al menos 5 veces superior. Conclusiones. La biopsia excisional de las lesiones primarias de mama no parece modificar el patrón del drenaje linfático superficial desde la areola de la mama, pudiendo realizarse el estudio del ganglio centinela tras esta intervención, utilizando la técnica periareolar superficial(AU)

Objective. A major controversial issue in the sentinel node biopsy of the breast is the applicability of sentinel node mapping in patients with the history of previous excisional biopsy of the breast lesions. In the current study, we evaluated the reproducibility of lymphoscintigraphy before and after excisional biopsy of the primary breast lesions using superficial peri-areolar injection of the radiotracer. Material and methods. Eighteen patients scheduled for excisional biopsy of breast lesions were included into the study. The patients received intra-dermal injection of the radiotracer in the peri-areolar area of the index quadrant 1 to 2h before surgery. Imaging was performed the day after surgery. Immediately after completion of the first imaging, the patients received another injection of the radiotracer with the same technique, dose, and location. Other sets of lymphoscintigraphy imaging were taken immediately and 4h post second injection. The two sets of lymphoscintigraphy images were compared. Results. In 2 patients, sentinel node could not be identified in either set of images. In the remaining 16 patients, one sentinel node was detected in both lymphoscintigraphy image sets. The sentinel nodes of the second image sets were all in the same location of the first sets with at least 5 times higher count. Conclusions. Excisional biopsy of the primary breast lesions does not seem to change the superficial lymphatic drainage pattern from the areola of the breast and sentinel node mapping can be performed after this procedure using superficial periareolar technique(AU)

Results of a national training programme in sentinel lymph node biopsy for breast cancer.

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 ((99m) Tc-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.

Reproducibility of lymphoscintigraphy before and after excisional biopsy of primary breast lesions: a study using superficial peri-areolar injection of the radiotracer.

OBJECTIVE: A major controversial issue in the sentinel node biopsy of the breast is the applicability of sentinel node mapping in patients with the history of previous excisional biopsy of the breast lesions. In the current study, we evaluated the reproducibility of lymphoscintigraphy before and after excisional biopsy of the primary breast lesions using superficial peri-areolar injection of the radiotracer. MATERIAL AND METHODS: Eighteen patients scheduled for excisional biopsy of breast lesions were included into the study. The patients received intra-dermal injection of the radiotracer in the peri-areolar area of the index quadrant 1 to 2h before surgery. Imaging was performed the day after surgery. Immediately after completion of the first imaging, the patients received another injection of the radiotracer with the same technique, dose, and location. Other sets of lymphoscintigraphy imaging were taken immediately and 4h post second injection. The two sets of lymphoscintigraphy images were compared. RESULTS: In 2 patients, sentinel node could not be identified in either set of images. In the remaining 16 patients, one sentinel node was detected in both lymphoscintigraphy image sets. The sentinel nodes of the second image sets were all in the same location of the first sets with at least 5 times higher count. CONCLUSIONS: Excisional biopsy of the primary breast lesions does not seem to change the superficial lymphatic drainage pattern from the areola of the breast and sentinel node mapping can be performed after this procedure using superficial periareolar technique.

The accuracy of sentinel node biopsy in breast cancer patients with the history of previous surgical biopsy of the primary lesion: systematic review and meta-analysis of the literature.

BACKGROUND: One of the subjects under debate in sentinel node mapping is the eligibility of patients with the history of previous surgical biopsy of the primary lesion for sentinel node biopsy. In the current systematic review, we evaluated the false negative and detection rates of sentinel node biopsy in breast cancer patients with and without previous surgical manipulation of the primary breast lesions. METHODS: Pubmed, SCOPUS, and Google scholar were searched for any relevant study with head to head comparison of patients with and without history of previous surgical manipulation of the primary breast lesions. The outcomes of interest were detection and false negative rates in each group, and odds ratio as well as risk difference of having sentinel node detection failure or getting false negative results in the surgical biopsy compared to the non-surgical biopsy group. RESULTS: 18 studies for false negative rate and 68 studies for detection rate evaluation were included in this review. Pooled detection rates for patients with and without previous surgical biopsy were 91.3% and 92.8%. Odds ratio and risk difference of having detection failure during surgery were 1.16 and 0.002 respectively. Pooled false negative rates for patients with and without previous surgical biopsy were 12.3% and 9.9%. Odds ratio and risk difference of having false negative results were 1.4 and 0.02 respectively. CONCLUSION: Surgical biopsy of the primary breast malignant lesions does not affect the detection rate of sentinel lymph node biopsy procedure. However, false negative rate seems to be slightly higher. We believe that the advantages of sentinel node biopsy outweigh this small difference.

Radiation protection for an intra-operative X-ray device.

OBJECTIVES: Therapeutic partial breast irradiation can be delivered intra-operatively using the Intrabeam 50 kVp compact X-ray device. Spherical applicators are added to the source to give an isotropic radiation dose. The low energy of this unit leads to rapid attenuation with distance, but dose rates are much greater than for diagnostic procedures. METHODS: To investigate the shielding requirements for this unit, attenuation measurements were carried out with manufacturer-provided tungsten-rubber sheets, lead, plasterboard and bricks. A prospective environmental dose rate survey was also conducted in the designated theatre. RESULTS: As a result of isotropic geometry, the scattered dose around shielding can be 1% of primary and thus often dominates measured dose rates compared with transmission. The absorbed dose rate of the unshielded source at 1 m was 11.6 mGy h(-1) but this was reduced by 95% with the shielding sheets. Measured values for the common shielding materials were similar to reference data for the attenuation of a 50 kVp diagnostic X-ray beam. Two lead screens were constructed to shield operators remaining in the theatre and an air vent into a service corridor. A lead apron would also provide suitable attenuation, although a screen allows greater flexibility for treatment operators. With these measures, staff doses were reduced to negligible quantities. Survey measurements taken during patient treatments confirmed no additional measures were required, but the theatre should be a controlled area and access restricted. CONCLUSION: Results from this study and reference data can be used for planning other facilities.

Religious coping strategies in patients diagnosed with breast cancer in the UK.

OBJECTIVES: The use of religious/spiritual coping strategies may be particularly prevalent when dealing with the stress of a cancer diagnosis. There has, however, been very little research conducted on this topic outside the USA. Existing measures of coping largely ignore the complexity of religious/spiritual coping and its potential to be adaptive as well as maladaptive. The aim of this study was to examine the prevalence of various religious coping strategies in a UK cancer sample. METHOD: A longitudinal design assessed religious coping strategies in patients newly diagnosed with breast cancer at the time of surgery and at 3 and 12 months post surgery. We recruited 202 patients of which, at 12 months, 160 remained. A non-religious coping measure was included for comparison. RESULTS: The use of religious coping strategies was overall common; up to 73% of patients used positive religious coping to some degree at surgery and up to 53% experienced various religious/spiritual struggles. The use of some religious coping strategies showed differing patterns of change across time while others remained stable. CONCLUSION: Using religious/spiritual resources in the coping process during the early stages of breast cancer appears common in the UK. Patients may benefit from having their spiritual needs addressed as experiencing some form of religious/spiritual struggle may serve as a barrier to illness adjustment. Health-care professionals should also be aware that some religious coping strategies may be more prevalent at different times during the first year of illness.

The impact of a breast cancer diagnosis on religious/spiritual beliefs and practices in the UK.

The use of religious/spiritual resources may increase when dealing with the stress of a cancer diagnosis. However, there has been very little research conducted into changes in religious/spiritual beliefs and practices as a result of a cancer diagnosis outside the USA. The aim of this study was to examine the impact of a breast cancer diagnosis on patients' religious/spiritual beliefs and practices in the UK where religious practice is different. The study used two methods. One compared the religious/spiritual beliefs and practices of 202 patients newly diagnosed with breast cancer with those of a control group of healthy women (n = 110). The other examined patients' perceived change in religious/spiritual beliefs and practices at the time of surgery with those in the year prior to surgery. The aspects of religiousness/spirituality assessed were: levels of religiosity/spirituality, strength of faith, belief in God as well as private and public practices. Patient's perceived their belief in God, strength of faith and private religious/spiritual practices to have significantly increased shortly after surgery compared with the year prior to surgery. However, there were no significant differences in religious/spiritual beliefs and practices between patients and healthy participants. Change scores demonstrated both a reduction and an increase in religious/spiritual beliefs and practices. Although belief in God, strength of faith and private religious/spiritual practices were perceived by patients to be significantly higher after their cancer diagnosis, no significant differences in religious/spiritual beliefs and practices were found between the cancer group at the time of surgery and the control group. Different methodologies appear to produce different results and may explain contradictions in past US studies. Limitations of this study are discussed and suggestions for future research are made.

Optical scanning for rapid intraoperative diagnosis of sentinel node metastases in breast cancer.

BACKGROUND: Intraoperative diagnosis of sentinel node metastases enables an immediate decision to proceed to axillary lymph node dissection, avoiding a second operation in node-positive women with breast cancer. METHODS: An optical scanner was developed that interrogated the cut surface of bivalved, but otherwise unprocessed, sentinel lymph nodes with pulses of white light by elastic scattering spectroscopy (ESS). The scattered light underwent spectral analysis, and individual spectra were initially correlated with conventional histology to develop a diagnostic algorithm. This algorithm was used to create false colour-coded maps of scans from an independent set of nodes, and the optimal criteria for discriminating between normal and cancer spectra were defined statistically. RESULTS: The discriminant algorithm was developed from a training set of 2989 spectra obtained from 30 metastatic and 331 normal nodes. Subsequent scans from 129 independent nodes were analysed. The scanner detected macrometastases (larger than 2 mm) with a sensitivity of 76 per cent (69 per cent including micrometastases) and specificity of 96 per cent. CONCLUSION: In this proof-of-principle study, the ESS results were comparable with current intraoperative diagnostic techniques of lymph node assessment.

Comparison of three mathematical models for predicting the risk of additional axillary nodal metastases after positive sentinel lymph node biopsy in early breast cancer.

BACKGROUND: Women with breast cancer and a positive axillary sentinel lymph node (SLN) are recommended to undergo complete axillary lymph node dissection; however, further nodal disease is not always present. Mathematical models have been constructed to determine the risk of metastatic disease; three of these were evaluated independently. METHODS: Data from 108 women with breast cancer who had a positive SLN biopsy and completion axillary lymph node dissection were used. Measurements of additional parameters over those usually determined (such as size of SLN metastasis) were assessed under the supervision of two pathologists. These data were used to determine the predicted risk of non-SLN metastases using three mathematical models (from Memorial Sloan-Kettering Cancer Center (MSKCC), Cambridge University and Stanford University) and a comparison made with the observed findings. Analyses were made using the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: Some 53 (49.1 per cent) of 108 patients had a positive non-sentinel axillary lymph node metastasis. The AUC values were 0.63, 0.72 and 0.67 for the MSKCC, Cambridge and Stanford nomograms respectively. CONCLUSION: This independent comparison found no significant difference between the models, although the Cambridge model had the advantage of requiring fewer measurements with a more accurate predictive performance.

Establishing axillary Sentinel Lymph Node Biopsy (SLNB) for early breast cancer in the United Kingdom: a survey of the national training program.

INTRODUCTION: The UK National training programme (NEWSTART) for SLNB in breast cancer was established in 2004, aimed at providing structured, standardised training with a focus on multidisciplinary team (MDT) delivery. METHODOLOGY: A questionnaire was devised and after approval by the Association of Breast Surgeons (ABS) executive committee they were sent to all full members of the ABS. RESULTS: Most (97%) of breast surgeons are convinced by the evidence for SLNB as standard of care for early breast cancer. 64% use SLNB to stage clinically node negative patients, of whom 23% use it as a standalone procedure. 38% of surgeons were dissatisfied with the time it takes to complete the in house training, and 87% with the time it takes to complete the validation phase. Logistical and funding issues were the main problems cited. The majority of surgeons (86%) use the recommended combined technique, with 47% continuing to use the dual localisation method. 14% use either blue dye or isotope alone, without scintiscan. Only 10% offer intra operative diagnosis, of which the majority (6%) use touch imprint cytology. 31% included their results in their most recent surgical appraisal. CONCLUSIONS: The majority of breast surgeons in the UK are convinced by the evidence for SLNB, and most use SLNB in their practice for staging. Reasons for not conducting SLNB are logistical rather than lack of belief in the procedure. The majority of respondents completed their training within the anticipated time line. The majority of centres do not perform intra-operative assessment.

Current status and advances in management of early breast cancer.

Breast cancer is the most common female cancer. Worldwide, more than a million women are diagnosed every year. However despite this increase, the mortality rate is declining. This is due to combination of factors including early diagnosis and effective treatment. This manuscript which is presented in two sections outlines the current status in management of early breast cancer. Section 1 focuses on the advances in diagnosis and surgical treatment of breast cancer and give an overview of the histopathological aspects. The focus of section 2 is on advances on adjuvant treatment of breast cancer including radiotherapy, chemotherapy and endocrine treatment.

Sentinel node imaging in breast cancer using superficial injections: technical details and observations.

INTRODUCTION: Sentinel lymph node (SLN) biopsy is the evolving standard of care for the management of early breast cancer. Accurate identification of the SLN is paramount for success of this procedure. Various techniques are described for SLN identification, but the superficial injection techniques, advocated by the UK National Training Programme (NEW START), are validated, reproducible and rapid. Pre-operative lymphoscintigraphy provides a road map for the surgeon and requires a reporting template. METHODS: As one of the NEW START training institutions in the UK practising this technique, we reviewed a mature series of 100 unselected, consecutive SLN lymphoscintigraphy procedures. We correlated the imaging, operative and pathology findings and have provided technical details of the technique and a template for reporting SLN lymphoscintigrams. RESULTS: The SLN localisation rate was 99% with one failed imaging. Seven patients required delayed imaging. The mean activity of the radiocolloid injected was 14.4MBq (range 8.3-23 MBq). The SLNs were visualised in the ipsilateral axilla in 98 images, intramammary in 3, and internal mammary in 1. A mean of 1.35 nodes were classified as 'True' SLNs on imaging criteria. Intra-operatively, a mean of 1.91 SLNs were excised. 32 of 116 hot and blue nodes, 7 of 15 only blue nodes, 13 of 47 only hot and 7 of 13 parasentinel nodes harboured metastases. CONCLUSION: The NEW START recommended, combined superficial injection techniques, have high localisation rates. Pre-operative sentinel node imaging is recommended and a template for reporting is provided.

Lignans and breast cancer risk in pre- and post-menopausal women: meta-analyses of observational studies.

Phyto-oestrogens are plant compounds structurally similar to oestradiol, which have been proposed to have protective effects against breast cancer. The main class of phyto-oestrogens in the Western diet is lignans. Literature reports on the effect of lignans in breast cancer risk have been conflicting. We performed three separate meta-analyses to examine the relationships between (i) plant lignan intake, (ii) enterolignan exposure and (iii) blood enterolactone levels and breast cancer risk. Medline, BIOSIS and EMBASE databases were searched for publications up to 30 September 2008, and 23 studies were included in the random effects meta-analyses. Overall, there was little association between high plant lignan intake and breast cancer risk (11 studies, combined odds ratio (OR): 0.93, 95% confidence interval (95% CI): 0.83-1.03, P=0.15), but this association was subjected to marked heterogeneity (I(2)=44%). Restricting the analysis to post-menopausal women, high levels of plant lignan intake were associated with reduced breast cancer risk (7 studies, combined OR: 0.85, 95% CI: 0.78, 0.93, P<0.001) and heterogeneity was markedly reduced (I(2)=0%). High enterolignan exposure was also associated with breast cancer (5 studies, combined OR: 0.73, 95% CI: 0.57, 0.92, P=0.009) but, again, there was marked heterogeneity (I(2)=63%). No association was found with blood enterolactone levels (combined OR: 0.82, 95% CI: 0.59-1.14, P=0.24). In conclusion, plant lignans may be associated with a small reduction in post-menopausal breast cancer risk, but further studies are required to confirm these results.

Impact of rapid molecular screening for meticillin-resistant Staphylococcus aureus in surgical wards.

BACKGROUND: This study aimed to establish the feasibility and cost-effectiveness of rapid molecular screening for hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) in surgical patients within a teaching hospital. METHODS: In 2006, nasal swabs were obtained before surgery from all patients undergoing elective and emergency procedures, and screened for MRSA using a rapid molecular technique. MRSA-positive patients were started on suppression therapy of mupirocin nasal ointment (2 per cent) and undiluted chlorhexidine gluconate bodywash. RESULTS: A total of 18,810 samples were processed, of which 850 (4.5 per cent) were MRSA positive. In comparison to the annual mean for the preceding 6 years, MRSA bacteraemia fell by 38.5 per cent (P < 0.001), and MRSA wound isolates fell by 12.7 per cent (P = 0.031). The reduction in MRSA bacteraemia and wound infection was equivalent to a saving of 3.78 beds per year (276,220 pounds sterling), compared with the annual mean for the preceding 6 years. The cost of screening was 302,500 pounds sterling, making a net loss of 26,280 pounds sterling. Compared with 2005, however, there was a net saving of 545,486 pounds sterling. CONCLUSION: Rapid MRSA screening of all surgical admissions resulted in a significant reduction in staphylococcal bacteraemia during the screening period, although a causal link cannot be established.

Breast-conserving surgery with intra-operative radiotherapy: the right approach for the 21st century?

Wide local excision followed by external beam radiation therapy (EBRT) to the whole breast has become the standard of care for most patients with localised 'early' breast cancer in the UK, Europe, and the USA. Local relapse rates are low, and overall survival figures have improved during the past decade, with the advent of more effective systemic endocrine- and chemo-therapy. A policy of EBRT for every patient undergoing breast conserving surgery (BCS) is however associated with a number of practical difficulties, acute radiation side effects and longer term toxicity, all of which detract from the obvious benefits of EBRT. In addition, with a disease as common as early breast cancer and a treatment programme typically requiring sophisticated radiation planning and many fractions of treatment, the policy of BCS plus EBRT has enormous resource implications within departments of oncology, greatly contributing to lengthy pre-treatment delays. For all these reasons, we and others have developed an increasing interest in techniques of partial breast irradiation, with an emphasis in our own Department on the emerging technique of intra-operative radiotherapy (IORT), which we initially employed as a boost to the tumour bed for use in conjunction with EBRT to the whole breast. To test the possibility of replacing the whole of the EBRT 3-6 week programme by a single application of IORT at the time of surgery, we and others have commenced a large scale prospectively randomised clinical trail in selected patients. Nine international centres are currently participating, and 350 patients have now been randomised to receive either IORT as part of the initial surgical excision or conventional EBRT with a pragmatic dose policy according to the preference of the contributing centre. The majority of patients undergoing IORT receive this at the time of initial surgery but it is also permissible within the trial programme to randomise suitable patients after the excised specimen has been histologically examined, thus avoiding any unsuitable patients - for example, those with a lobular carcinoma. These patients will be stratified and assessed separately from the 'pre-pathology' group, whose surgery and IORT is completed within a single session; if the latter patients are found to have unfavourable histology we have the facility, within the trial, to add EBRT. The trial is ongoing and our early experience has been encouraging. We have also recently assessed the long term local failure rate in patients offered IORT as a tumour bed boost, in conjunction with conventional EBRT. This methodology will also be the subject of a future randomised clinical trial.