Progression of breast cancer following locoregional ipsilateral recurrence: importance of interval time.

BACKGROUND: Studies comparing prognosis of breast cancer (BC) patients with and without locoregional recurrence (LR) present conflicting results. We aimed to improve our understanding of the impact of LR on prognosis by examining a large cohort of patients treated at Guy's and St Thomas' NHS Foundation Trust. METHODS: Risk factors associated with BC-specific death were investigated using Cox proportional hazards regression in 5199 women diagnosed between 1975 and 2007. Breast cancer-specific death following LR was assessed with Poisson regression. RESULTS: Overall, 552 women (11%) developed LR, with a median follow-up time of 4.28 years. Known factors associated with BC-specific death (tumour stage, grade, and nodal status) were of significance in our data. Women with a shorter disease-free interval had a worse prognosis. For instance, the HR for BC-specific death among women undergoing mastectomy with an LR 0.5-1 year after diagnosis of their primary tumour was 6.67 (95% CI: 3.71-11.99), when compared with women who did not experience LR. CONCLUSIONS: It often remains difficult to distinguish between a genuine LR and a new primary. The HRs for risk of BC-specific death following a second lesion suggest that they may act as a marker of systemic disease, large tumour burden, or depleted host defence. The clinically highly relevant impairment in prognosis calls for further research into the underlying mechanisms. We showed that for at least 15 years of follow-up, the prognosis in women following the occurrence of an LR may benefit from careful diagnostic and therapeutic management.

Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review.

The existing standard for axillary lymph node staging in breast cancer patients with a clinically and radiologically normal axilla is sentinel lymph node biopsy with a radioisotope and blue dye (dual technique). The dependence on radioisotopes means that uptake of the procedure is limited to only about 60% of eligible patients in developed countries and is negligible elsewhere. We did a systematic review to assess three techniques for sentinel lymph node biopsy that are not radioisotope dependent or that refine the existing method: indocyanine green fluorescence, contrast-enhanced ultrasound using microbubbles, and superparamagnetic iron oxide nanoparticles. Our systematic review suggested that these new methods for sentinel lymph node biopsy have clinical potential but give high levels of false-negative results. We could not identify any technique that challenged the existing standard procedure. Further assessment of these techniques against the standard dual technique in randomised trials is needed.

The growing burden of cancer in India: epidemiology and social context.

Cancer can have profound social and economic consequences for people in India, often leading to family impoverishment and societal inequity. Reported age-adjusted incidence rates for cancer are still quite low in the demographically young country. Slightly more than 1 million new cases of cancer are diagnosed every year in a population of 1.2 billion. In age-adjusted terms this represents a combined male and female incidence of about a quarter of that recorded in western Europe. However, an estimated 600,000-700,000 deaths in India were caused by cancer in 2012. In age-standardised terms this figure is close to the mortality burden seen in high-income countries. Such figures are partly indicative of low rates of early-stage detection and poor treatment outcomes. Many cancer cases in India are associated with tobacco use, infections, and other avoidable causes. Social factors, especially inequalities, are major determinants of India's cancer burden, with poorer people more likely to die from cancer before the age of 70 years than those who are more affluent. In this first of three papers, we examine the complex epidemiology of cancer, the future burden, and the dominant sociopolitical themes relating to cancer in India.

Cancer research in India: national priorities, global results.

Over the past 20 years, cancer research in India has grown in size and impact. Clinicians, scientists, and government and state policy makers in India have championed cancer research, from studies to achieve low-tech, large-scale health outcomes to some of the most advanced areas of fundamental cancer science. In this paper, we frame public policy discussions about cancer with use of an in-depth analysis of research publications from India. Cancer research in India is a complex environment that needs to balance public policy across many competing agendas. We identify major needs across these environments such as those for increased research capacity and training and protected time for clinical researchers; for more support from states and enhanced collaborative funding programmes from government; for development of national infrastructures across a range of domains (ie, clinical trials, tissue banking, registries, etc); and for a streamlined and rational regulatory environment. We also discuss improvements that should be made to translate research into improvements in cancer outcomes and public health.

The state of research and development in global cancer surgery.

OBJECTIVE: The objective of this study was to perform an analysis of global cancer surgery research and development trends over the last 10 years across 21 countries. BACKGROUND: Surgery is the main modality for cancer cure and control globally. Yet, in comparison to other areas such as cancer drugs, we know little about ongoing research activities to inform policymakers. METHODS: Two subfield filters, surgery research and oncology, were developed and applied to Web of Science. The intersection of these 2 filters identified papers in surgical oncology, and their bibliographic details were downloaded for analysis. This included matching of 5-year citation counts to the papers, impact factor, geographical analysis by country, translational collaboration, involvement in clinical trials, citation on clinical guidelines, and percentage of reviews. RESULT: Surgical oncology represents about 9% of all cancer research-low in comparison with surgery's contribution to cancer treatment. The US published the most, followed by Japan which had a high relative commitment to surgery within cancer research, followed by the large West European countries. Although Sweden's papers were relatively basic, it participated the most in clinical trials. Its papers were also the most cited on clinical guidelines, but contained relatively few reviews, where the UK, Greece, and Belgium scored best. Surgical oncology papers are generally not well cited compared with cancer research overall, but on this measure the Netherlands, the US, and Sweden scored best. International collaboration was measured relative to what might have been expected, on this indicator Canada, Switzerland, and the US were the best performers. CONCLUSIONS: Globally, low activity-low funding cycle needs to be addressed by new national and supranational policies to support surgical oncology research.

Delivering affordable cancer care in high-income countries.

The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.

Axillary lymph node drainage pathways from intradermal and intraparenchymal breast planes.

BACKGROUND: To compare functional anatomy of breast peri-areolar and peri-tumoral lymphatic drainage basins. METHODS: Fifteen breast cancer patients received simultaneous peri-areolar (intradermal) and peri-tumoral (intraparenchymal) injections of human polyclonal immunoglobulin (HIG) labeled with (99m)Tc and (111)In 2 to 4 h before axillary lymph node clearance surgery. Resected nodes (range 5-20; median 16) were individually counted for (99m)Tc and (111)In in a well-counter and ranked according to activity content (echelon). Activity in distal nodes was negligible so extraction efficiency (E) of HIG in the first echelon node was calculated as counts divided by total counts in the chain. RESULTS: Five- to 10-fold more activity was recovered after intradermal injection. The injection planes identified the same first echelon node in 10 patients (group 1) but different in five (group 2). In group 1, intradermal E correlated with intra-parenchymal E (r = 0.82; P < 0.01). E of intradermal first echelon nodes in group 2 was 51 (SD 13)%, similar to intradermal E in group 1 (58 [23]%). E of intraparenchymal first echelon nodes in group 2, however, was 28 (6)%, lower than intraparenchymal E in group 1 (54 [20]%; P < 0.02). CONCLUSIONS: Lymph nodes extract approximately 50% of HIG. Extracted HIG does not cascade to distal nodes, validating HIG for sentinel node lymphoscintigraphy. HIG injected intradermally at the areola drains via a single route to the axilla. In two-thirds of patients, peri-tumoral HIG follows a similar route, but in one-third of patients drainage from the parenchymal plane is more complex, with more than one route to the axilla.

Measurement of lymph node function from the extraction of immunoglobulin in lymph.

BACKGROUND: We aimed to measure the extraction fraction of human immunoglobulin G (HIG) by the 1st echelon lymph node (sentinel node) following intradermal injection in patients with breast cancer undergoing axillary lymph node dissection (ALND) and examine its association with node size and presence and extent of nodal metastatic disease. MATERIALS AND METHODS: HIG labelled with either In-111 (n = 21) or Tc-99m (n = 9) was injected intradermally at the areolar. ALND was performed 2-4 h later. All lymph nodes were isolated and individually counted in a well-counter. The counts in the 'hottest' (1st echelon) node were expressed as a fraction of total counts in all the resected nodes. Since counts in the least hot nodes barely exceeded background, this fraction represents extraction fraction for the 1st echelon node. Presence of disease was noted in each 1st echelon node and the extent quantified as percentage replacement with disease. RESULTS: Median extraction fraction in 1st echelon nodes with no or low (<1%) disease burden (n = 21) was 68 (range 23-93)%, significantly higher (p < 0.05) than in diseased 1st echelon nodes (n = 9), in which it was 44 (21-66)%. There was, however, no association between extraction fraction in diseased nodes and disease extent. In nodes with no/low disease, extraction fraction was similar for the two radiolabels. There was no association between extraction fraction and node size. CONCLUSION: Nodal extraction fraction of HIG is a novel physiological measurement. It is reduced as a result of metastatic invasion. In the absence of disease, it shows no correlation with node size.

Imaging of lymphatic vessels in breast cancer-related lymphedema: intradermal versus subcutaneous injection of 99mTc-immunoglobulin.

OBJECTIVE: The disordered physiology that results from axillary lymph node clearance surgery for breast cancer and that leads to breast cancer-related lymphedema is poorly understood. Rerouting of lymph around the axilla or through new pathways in the axilla may protect women from breast cancer-related lymphedema. The aim of the study was to compare intradermal with subcutaneous injection of technetium-99m ((99m)Tc)-labeled human polyclonal IgG (HIG) with respect to lymphatic vessel imaging. MATERIALS AND METHODS: Six women with breast cancer-related lymphedema underwent unilateral upper limb lymphoscintigraphy, using a web space injection of (99m)Tc-labeled HIG, after intradermal and subcutaneous injections on separate occasions. Multiple sequential images were obtained of the affected upper limb and torso over 3 hr on each occasion. Accumulation of activity in blood was quantified from venous blood samples taken from the opposite arm. RESULTS: Imaging after intradermal injection clearly showed discrete lymphatic vessels in five of six patients, in contrast to imaging after subcutaneous injection, which did not show any discrete vessels in any patient. Intradermal injection resulted in more rapid visualization of cutaneous lymph rerouting than subcutaneous injection in six of six patients. Recovery of injected (99m)Tc-labeled HIG in venous blood was greater after intradermal injection in six of six patients. CONCLUSION: In patients with breast cancer-related lymphedema, lymphatic vessels are more clearly depicted after intradermal than subcutaneous injection as a result of direct access of radiotracer to dermal lymphatics. This finding has implications for imaging lymphatic vessel regeneration and lymph rerouting.

Constitutively Enhanced Lymphatic Pumping in the Upper Limbs of Women Who Later Develop Breast Cancer-Related Lymphedema.

BACKGROUND: It has previously been shown that the lymph drainage rate in both upper limbs is greater in women destined to develop breast cancer-related lymphedema (BCRL) than in those who do not develop BCRL, indicating a constitutive predisposition. We explored constitutive differences further by measuring the maximum lymphatic pump pressure (Ppump) and the rate of (99m)Tc-Nanocoll transport generated by the contractile upper limb lymphatics before and after breast cancer surgery in a group of women who were followed for 2 years to determine their eventual BCRL or non-BCRL status. METHODS AND RESULTS: Ppump and tracer transport rate were measured by lymphatic congestion lymphoscintigraphy in the ipsilateral upper limb in 26 women pre- and post-breast cancer surgery. BCRL occurred in 10/26 (38.5%) cases. Ppump in the women who later developed BCRL (40.0 ± 8.2 mmHg) was 1.7-fold higher than in those who did not develop BCRL (23.1 ± 10.8 mmHg, p = 0.001). Moreover, the rate of lymph tracer transport into the forearm was 2.2-fold greater in the women who later developed BCRL (p = 0.052). Surgery did not significantly reduce Ppump measured 21 weeks postsurgery, but impaired forearm tracer transport in pre-BCRL women by 58% (p = 0.047), although not in those who did not develop BCRL. CONCLUSIONS: Women destined to develop BCRL have higher pumping pressures and lymph transport, indicating harder-working lymphatics before cancer treatment. Axillary lymphatic damage from surgery appears to compromise lymph drainage in those women constitutively predisposed to higher lymphatic pressures and lymph transport.

Family history of breast cancer and its association with disease severity and mortality.

A family history (FH) of breast cancer (BC) is known to increase an individual's risk of disease onset. However, its role in disease severity and mortality is less clear. We aimed to ascertain associations between FH of BC, severity and BC-specific mortality in a hospital-based cohort of 5354 women with prospective information on FH. We included women diagnosed at Guy's and St Thomas' NHS Foundation Trust between 1975 and 2012 (n = 5354). BC severity was defined and categorized as good, moderate, and poor prognosis. Data on BC-specific mortality was obtained from the National Cancer Registry and medical records. Associations between FH and disease severity or BC-specific mortality were evaluated using proportional odds models and Cox proportional hazard regression models, respectively. Available data allowed adjustment for potential confounders (e.g., treatment, socioeconomic status, and ethnicity). FH of any degree was not associated with disease severity at time of diagnosis (adjusted proportional OR: 1.00 [95% CI: 0.85 to 1.17]), which remained true also after stratification by period of diagnosis. FH of BC was not associated with BC-mortality HR: 0.99 (95% CI: 0.93 to 1.05). We did not find evidence to support an association between FH of BC and severity and BC-specific mortality. Our results indicate that clinical management should not differ between women with and without FH, when the underlying mutation is unknown.

Local vascular access of radioprotein injected subcutaneously in healthy subjects and patients with breast cancer-related lymphedema.

UNLABELLED: The aim of the study was to use dual-isotope lymphoscintigraphy in healthy volunteers and women with breast cancer-related lymphedema (BCRL) to detect and quantify transport of radiolabeled protein from a subcutaneous injection depot to local blood vessels as a potential mechanism of protection against edema resulting from treatment to the axilla. METHODS: A total of 29 subjects and 18 women with a history of BCRL received bilateral subcutaneous injections of human IgG (HIgG) in the second dorsal web space of each hand, (99m)Tc-HIgG on one side and (111)In-HIgG on the other. In 8 further healthy subjects, epinephrine was administered with the labeled HIgG. Radioactivity at each depot was measured at regular intervals for a total of 3 h using a collimated sodium iodide scintillation detector, and radioactivity in venous blood sampled from both arms was measured using an automatic sample counter. Ipsilateral blood time-concentration curves were corrected for recirculating activity by subtraction of the simultaneous contralateral concentration, to define the component of ipsilateral blood resulting from local vascular access of radioprotein. Accumulation of activity in blood was expressed in relation to injected activity and activity that had left the depot and was calculated as a function of time-in systemic blood, by multiplying contralateral concentrations by an estimate of the subject's blood volume, and in ipsilateral blood, by using indicator dilution theory and an assumed forearm blood flow of 20 mL/min. RESULTS: (99m)Tc-HIgG and (111)In-HIgG behave almost identically with respect to depot clearance and accumulation in contralateral venous blood, with or without epinephrine, which reduced both depot clearance and blood accumulation rate. Moreover, a side-to-side correlation with respect to contralateral accumulation was present in healthy subjects, was not abolished by epinephrine, and was maintained in the face of asymmetric accumulation in BCRL. Contralateral accumulation of radioprotein was reduced in BCRL after injection into the affected side only when the hand was involved. In contrast to contralateral sampling, ipsilateral time-concentration and accumulation profiles were consistent with instability of (111)In-HIgG and rapid local vascular access of small amounts of protein-free (111)In. Experiments based on precipitation of protein with trichloroacetic acid confirmed relatively high levels of unbound ipsilateral (111)In, especially in samples obtained early after injection. Substantial accumulation of protein-bound (99m)Tc was observed in ipsilateral blood, with a time course similar to that of contralateral accumulation. Positive correlation between ipsilateral and contralateral blood (99m)Tc activity was observed at all time points, often significantly, in contrast to (111)In, for which it was negative at all time points. Ipsilateral accumulation of (99m)Tc adjusted for activity that had left the depot was unchanged with respect to the affected arm in BCRL patients. CONCLUSION: Whereas (111)In-HIgG and (99m)Tc-HigG are interchangeable for measurement of depot clearance and contralateral venous accumulation rates, ipsilateral sampling is much more sensitive to protein-free radionuclide and detects significant differences resulting from some instability of (111)In-HIgG. On the basis of (99m)Tc data, there appears to be substantial local vascular access of radioprotein within the arm, both in healthy subjects and in patients with BCRL, through either lymphaticovenous communications or direct transendothelial transport.

Quantification of lymphatic function for investigation of lymphedema: depot clearance and rate of appearance of soluble macromolecules in blood.

UNLABELLED: The object of this study was to develop a new technique for the quantitative measurement of lymphatic function. The rate of clearance of radiolabeled protein from a subcutaneous depot is supplemented by measurement of the appearance of the protein in venous blood. This initial study was performed on normal arms, with a view to subsequent clinical application such as in the investigation of women with breast cancer--related lymphedema (BCRL). METHODS: Fourteen healthy volunteers (12 women, 2 men) and 8 women awaiting surgery for breast cancer were recruited for the study. Each received subcutaneous depot injection of protein solution in the second dorsal web space of each hand, labeled with (111)In on one side and with (99m)Tc on the other side. Human serum albumin (HSA) was the protein used in the first 8 subjects and human polyclonal immunoglobulin G (HIgG) was used thereafter. The activity at each depot was measured at regular intervals using a collimated sodium iodide scintillation detector, and the activity in venous blood sampled from both arms was measured in an automatic sample counter. RESULTS: (99m)Tc-HSA cleared from the depot consistently faster than (111)In-HSA (P = 0.001). The proportions of radionuclide remaining bound to protein in venous blood were higher for (99m)Tc than for (111)In. HIgG displayed improved labeling stability for both nuclides, reflected in equal rates of clearance. Blood activity rose steadily after an early latent phase and for HIgG correlated strongly with the rate of clearance from the depot (P < 0.001). Marked variation between individuals was observed. CONCLUSION: A dual-isotope technique relies on identical behavior of the 2 radiopharmaceuticals used. This study shows that this is the case with respect to HIgG but not HSA. (99m)Tc-HSA cleared faster than (111)In-HSA and yet displayed better in vivo labeling stability. We conclude that (111)In dissociates from HSA in the depot but then becomes locally bound. Using HIgG, a close correlation was observed between the rates of clearance from the depot and the appearance in venous blood. This finding suggests that HIgG would be a suitable marker for subsequent dual-isotope studies on women with BCRL.

Measurement of the extraction fractions of nanocolloid and polyclonal immunoglobulin by axillary lymph nodes in patients with breast cancer.

BACKGROUND: 99mTc nanocolloid (99mTc-NC) is the most widely used tracer for lymphoscintigraphy, although others have been proposed, including radiolabelled proteins such as human serum albumin and polyclonal human immunoglobulin G (HIG). The extraction fraction of such tracers by individual nodes is clearly important but has not previously been measured in humans. METHODS: Patients scheduled for axillary clearance surgery (three groups) received dual-labelled radiotracers 2-4 h before surgery: group 1 (3 patients) received 99mTc-NC (10 MBq) and 111In-HIG (2 MBq) as a mixture (0.2 ml) into the breast parenchyma above the primary tumour; group 2 (3 patients) received 99mTc-HIG (10 MBq) and 111In-HIG (2 MBq) as a mixture (0.2 ml) into the breast parenchyma above the primary tumour; and group 3 (4 patients) received 99mTc-HIG (10 MBq) and 111In-HIG (2 MBq) separately (both 0.2 ml) into the breast parenchyma above the tumour and the intradermal plane at the areola. All resected nodes were counted for Tc and In in a well-type scintillation counter. In group 1, nodes were ranked according to their Tc uptake. In groups 2 and 3, nodes were ranked separately according to their respective Tc and In uptakes. If nodes are arranged in linear order and each node extracts a constant fraction of incoming tracer, then the activity in the nodes would decrease exponentially with an individual nodal extraction fraction, E, equal to 1-e(-k), where k is the rate constant of decrease. RESULTS: In the first group, 99mTc-NC and 111In-HIG identified the same sentinel and second echelon nodes. The observed decrease in nodal activity was exponential in all groups, at least for the first five nodes. Average values for E, based on the first five nodes were 0.69 (range 0.57-0.89; n=3) for 99mTc-NC and 0.45 (0.15-0.70; n=17) for HIG (irrespective of label) (Wilcoxon rank sum, P=0.02). With respect to HIG, there was no significant difference in E between 99mTc and 111In or between deep and superficial injections in group 3. CONCLUSION: Although HIG has an extraction fraction less than 99mTc-NC, the value of E is still high enough to make HIG a useful tracer for lymphoscintigraphy, especially for identifying second echelon nodes in addition to sentinel nodes and for imaging lymphatic vessels as well as lymph nodes.

Challenges in the management of pleomorphic lobular carcinoma in situ of the breast.

BACKGROUND: Pleomorphic Lobular Carcinoma in Situ (PLCIS) is a pathological variant of Lobular Carcinoma in Situ (LCIS) with distinct features. Since first described over a decade ago there are only few papers published about this condition. METHODS: Medline and Pubmed based literature overview was done with the aim of describing the different histopathological, radiological and clinical features of this pathological entity to highlight the different clinicopathological presentations and modalities of treatment described. RESULTS: PLCIS has different biological features when compared to LCIS. It is more likely to be associated with invasive disease and the immuno-histochemical profile shows it is less likely to be ER and PR positive with higher positivity of HER2, Ki-67and p53. It has been suggested that PLCIS should be treated more aggressively than LCIS and surgically excised in similar fashion to DCIS. CONCLUSION: PLCIS is a more aggressive variant of LCIS that needs to be managed differently. Surgical excision with clear margins is advised. Further adjuvant treatments have been described in the literature with little evidence to support their use.

Delivery of radiolabelled blood cells to lymphatic vessels by intradermal injection: a means of investigating lymphovenous communications in the upper limb.

OBJECTIVE: To identify peripheral lymphovenous communications (LVCs) using labelled erythrocytes and intradermal injection. Intradermal injection delivers macromolecules to loco-regional lymph nodes faster than subcutaneous injection, suggesting easier lymphatic vessel access. METHODS: Autologous erythrocytes labelled with 111In and 99mTc were injected into opposite hands. In four normal volunteers, the differentially labelled cells were given by intradermal injection on one side and subcutaneous injection on the other while in four breast cancer patients they were given by intradermal injection bilaterally 3 months after axillary lymph node clearance surgery. The axillae were imaged and blood samples obtained bilaterally at approximately 15, 30, 60, 120 and 180 min post-injection. Plasma activity was subtracted from whole blood activity to obtain erythrocyte-bound activity and contralateral concentrations were subtracted from ipsilateral concentrations to correct for ipsilateral recirculation. From estimated blood volume, erythrocyte and plasma activities contralateral to the injected side were calculated as percentage administered activity. Tracer concentrations in ipsilateral samples (%/l) were integrated to give total percentage administered activity, assuming a forearm blood flow of 20 ml/min. RESULTS: Kinetics of plasma activity were consistent with small diffusible 99mTc complexes and protein-bound 111In. With both radionuclides, axillary nodes were visualized after intradermal but not subcutaneous injection, suggesting that nodal activity arises from erythrocytes. In one patient, 99mTc and 111In labelled erythrocytes accumulated in similar amounts ipsilaterally and contralaterally, suggesting bilateral LVCs distal to the ipsilateral sampling point. There was no evidence of LVCs in the other seven volunteers. CONCLUSION: Intradermally injected erythrocytes are able to detect and potentially quantify peripheral LVCs.

Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group.

The use of breast magnetic resonance imaging (MRI) is rapidly increasing. EUSOMA organised a workshop in Milan on 20-21st October 2008 to evaluate the evidence currently available on clinical value and indications for breast MRI. Twenty-three experts from the disciplines involved in breast disease management - including epidemiologists, geneticists, oncologists, radiologists, radiation oncologists, and surgeons - discussed the evidence for the use of this technology in plenary and focused sessions. This paper presents the consensus reached by this working group. General recommendations, technical requirements, methodology, and interpretation were firstly considered. For the following ten indications, an overview of the evidence, a list of recommendations, and a number of research issues were defined: staging before treatment planning; screening of high-risk women; evaluation of response to neoadjuvant chemotherapy; patients with breast augmentation or reconstruction; occult primary breast cancer; breast cancer recurrence; nipple discharge; characterisation of equivocal findings at conventional imaging; inflammatory breast cancer; and male breast. The working group strongly suggests that all breast cancer specialists cooperate for an optimal clinical use of this emerging technology and for future research, focusing on patient outcome as primary end-point.

Functional variation in lymph node arrangements within the axilla.

The aim of the project was to identify how lymphatic pathways are functionally arranged within the axilla (i.e., single linear chains, branching chains, and networks). We used ex vivo dual isotope radioassay of individual nodes resected at axillary lymphatic clearance surgery in breast cancer patients given simultaneous intradermal breast and intradermal hand injections (n = 15) or simultaneous intradermal breast and parenchymal breast injections (n = 15) of differentially labelled human immunoglobulin (Tc-99m-HIG and In-111-HIG). Nodes were ranked according to isotope content and activity-rank profiles constructed for each of the two injection sites. The majority of profiles following intradermal breast injection (17/30) were mono-exponential, consistent with a simple linear chain of nodes, with each node extracting a constant fraction of incoming HIG. In 15/17 of these, the accompanying profile from the alternative injection site was also mono-exponential and, in 11/15, essentially parallel. The profile appeared biphasic in 12/30 intradermal breast injections and of these 9/12 were accompanied by a biphasic profile (7/9 parallel) from the alternative injection site. In one patient, both profiles were polyphasic and parallel. Considering the respective shapes of paired profiles and whether the two injection sites shared the same first echelon nodes, functional lymph node arrangements are proposed. The commonest is a single linear chain, then a chain branching into two linear chains, and, least common, a network.