Multifocal and multicentric breast cancer, is it time to think again?

Multifocal multicentric breast cancer has traditionally been considered a contraindication to breast conserving surgery because of concerns regarding locoregional control and risk of disease recurrence. However, the evidence supporting this practice is limited. Increasingly, many breast surgeons are advocating breast conservation in selected cases. This short narrative review summarises current evidence on the role of surgery in multifocal multicentric breast cancer and shows that when technically feasible the option of breast conservation is oncologically safe.

A self-help diet and physical activity intervention with dietetic support for weight management in men treated for prostate cancer: pilot study of the Prostate Cancer Weight Management (PRO-MAN) randomised controlled trial.

Overweight and obesity may increase risk of disease progression in men with prostate cancer, but there have been few studies of weight loss interventions in this patient group. In this study overweight or obese men treated for prostate cancer were randomised to a self-help diet and activity intervention with telephone-based dietitian support or a wait-list mini-intervention group. The intervention group had an initial group meeting, a supporting letter from their urological consultant, three telephone dietitian consultations at 4-week intervals, a pedometer and access to web-based diet and physical activity resources. At 12 weeks, men in both groups were given digital scales for providing follow-up weight measurements, and the wait-list group received a mini-intervention of the supporting letter, a pedometer and access to the web-based resources. Sixty-two men were randomised; fifty-four completed baseline and 12-week measurements, and fifty-one and twenty-seven provided measurements at 6 and 12 months, respectively. In a repeated-measures model, mean difference in weight change between groups (wait-list mini-intervention minus intervention) at 12 weeks was -2·13 (95 % CI -3·44, -0·82) kg (P = 0·002). At 12 months the corresponding value was -2·43 (95 % CI -4·50, -0·37) kg (P = 0·022). Mean difference in global quality of life score change between groups at 12 weeks was 12·3 (95 % CI 4·93, 19·7) (P = 0·002); at 12 months there were no significant differences between groups. Results suggest the potential of self-help diet and physical activity intervention with trained support for modest but sustained weight loss in this patient group.

Regulation of fatty acid synthase (FAS) and apoptosis in estrogen-receptor positive and negative breast cancer cells by conjugated linoleic acids.

BACKGROUND: Conjugated linoleic acids (CLAs) are natural dairy food components that exhibit a unique body of potential health benefits in animals and man, including anti-cardiovascular disease and anti-cancer effects. Several studies have demonstrated that fatty acid synthase (FAS) levels (protein and mRNA) are over expressed in many carcinomas. Sterol regulatory element binding proteins (SREBPs) are transcription factors that regulate genes involved in lipid metabolism, including FAS. METHODS: Breast cancer cell lines, MCF-7 and MDA-MB-231 were treated with CLAs to investigate the regulation of SREBP-1c and FAS expression. RESULTS: In MDA-MB-231 cells, SREBP-1c and FAS were co-ordinately decreased by treatment with 25 µM CLA 9-11 and 10-12. In MCF-7 cells, the decrease in SREBP-1c and FAS expression was dependant on the concentration of CLA used. CONCLUSIONS: The data suggest a differential effect of CLAs on SREBP-1c and FAS in estrogen receptor-positive (MCF-7) compared to estrogen receptor-negative (MDA-MB-231) breast cancer cells.

Chronic preoperative pain and psychological robustness predict acute postoperative pain outcomes after surgery for breast cancer.

BACKGROUND: Few epidemiological studies have prospectively investigated preoperative and surgical risk factors for acute postoperative pain after surgery for breast cancer. We investigated demographic, psychological, pain-related and surgical risk factors in women undergoing resectional surgery for breast cancer. METHODS: Primary outcomes were pain severity, at rest (PAR) and movement-evoked pain (MEP), in the first postoperative week. RESULTS: In 338 women undergoing surgery, those with chronic preoperative pain were three times more likely to report moderate to severe MEP after breast cancer surgery (OR 3.18, 95% CI 1.45-6.99). Increased psychological 'robustness', a composite variable representing positive affect and dispositional optimism, was associated with lower intensity acute postoperative PAR (OR 0.63, 95% CI 0.48-0.82) and MEP (OR 0.71, 95% CI 0.54-0.93). Sentinel lymph node biopsy (SLNB) and intraoperative nerve division were associated with reduced postoperative pain. No relationship was found between preoperative neuropathic pain and acute pain outcomes; altered sensations and numbness postoperatively were more common after axillary sample or clearance compared with SLNB. CONCLUSION: Chronic preoperative pain, axillary surgery and psychological robustness significantly predicted acute pain outcomes after surgery for breast cancer. Preoperative identification and targeted intervention of subgroups at risk could enhance the recovery trajectory in cancer survivors.

The biological correlates of macroscopic breast tumour structure measured using fractal analysis in patients undergoing neoadjuvant chemotherapy.

Breast cancers are evolving, multi-scale systems that are characterized by varied complex spatial structures. In this study, we measured the structural characteristics of 33 breast tumours in patients who were to receive neoadjuvant chemotherapy using dynamic contrast enhanced MRI and fractal geometry. The results showed a significant association between fractal measurements and tumour characteristics. The fractal dimension was associated with receptor status (ER and PR) and the fractal fit was associated with response to chemotherapy, measured using a validated pathological response scale, tumour grade and size. This study describes structure measures that may be a consequence of known prognostic factors during the initial and/or maturation phase of tumour growth. These results suggest that measuring tumour structure in this way can predict an individual's response to neoadjuvant therapy and may identify those who will benefit least from neoadjuvant chemotherapy, allowing alternative treatment options to be selected in those patients.

Complementary and alternative medicines use by Scottish women with breast cancer. What, why and the potential for drug interactions?

BACKGROUND: Despite the increased use of complementary and alternative medicine (CAM) by breast cancer patients, there is little published information regarding CAM use in the Scottish breast cancer population. METHODS: A questionnaire comprising five sections--demographics; perceived health status, prescribed medicines; use, indications, satisfaction and expenditure on CAMs; attitudes towards and factors associated with CAM use; and attitudinal statements--was issued to patients attending the Aberdeen Breast Clinic. RESULTS: A total of 453 questionnaires were distributed and 360 (79.5%) returned. Respondents were prescribed a mean of 3.2 medicines (95% CI 2.83-3.47). With regard to CAM use, 33.1% of respondents reported current use, 36.4% prior use, and 30.6% reported never having used CAMs. The key indications for use were general well being, boosting immune system and cancer prophylaxis, with high levels of satisfaction reported. The strongest association for CAM use was use by friends and family and higher educational attainment (p < 0.001). Supplements with estrogenic activity, such as soya or red clover, were taken by 29% of respondents. Herbs (echinacea, pomegranate, peppermint, chamomile, grapefruit, garlic, ginseng) that have the potential to interact with adjuvant endocrine therapies (tamoxifen, anastrazole, letrozole, exemestane) were being taken by 38% of treated patients. CONCLUSION: The level of CAM use by Scottish breast cancer patients is similar to that reported from other countries, although there are marked differences in the type, nature and frequency of specific CAM therapies. Higher patient education level and use by family and friends were significantly associated with CAM use. The high level of use of potentially disease modifying or interacting herb supplements may be of concern.

Omega-3 N-acylethanolamines are endogenously synthesised from omega-3 fatty acids in different human prostate and breast cancer cell lines.

Omega-3 (n-3) fatty acids inhibit breast and prostate cancer cell growth. We previously showed that N-acylethanolamine derivatives of n-3 (n-3-NAE) are endocannabinoids, which regulate cancer cell proliferation. These n-3-NAE are synthesised in certain cells/tissues, after supplementing with fatty acids, however, no one has assessed whether and to what extent this occurs in cancer cells. We determined levels of endogenous n-3-NAEs in hormone sensitive and insensitive prostate and breast cancer cells and subsequent effects on other endocannabinoids (anandamide and 2-arachidonoylglycerol), before and after supplementing with DHA and EPA fatty acids, using HPLC tandem mass spectrometry. This is the first study reporting that n-3-NAEs are synthesised from their parent n-3 fatty acids in cancer cells, regardless of tumour type, hormone status or the presence of fatty acid amide hydrolase. This could have important implications for the use of n-3 fatty acids as therapeutic agents in breast and prostate cancers expressing cannabinoid receptors.

Moving inwards, moving outwards, moving upwards: the role of spirituality during the early stages of breast cancer.

The paper reflects on a study which explored the role of spirituality in the lives of women during the first year after being diagnosed with breast cancer. The study utilised a qualitative method (hermeneutic phenomenology) designed to provide rich and thick understanding of women's experiences of breast cancer and to explore possible ways in which spirituality may, or may not, be beneficial in enabling coping and enhancing quality of life. The paper draws on the thinking of David Hay and Viktor Frankl to develop a model of spirituality that includes, but is not defined by, religion and that has the possibility to facilitate effective empirical enquiry. It outlines a threefold movement - inwards, outwards and upwards - that emerged from in-depth interviews with women who have breast cancer. This framework captures something of the spiritual movement that women went through on their cancer journeys and offers some pointers and possibilities for better and more person-centred caring approaches that include recognition of the spiritual dimension of women's experiences for the management of those with breast cancer.

Impaired expression of glutathione peroxidase-4 gene in peripheral blood mononuclear cells: a biomarker of increased breast cancer risk.

Breast cancer aetiology is unclear despite comprising approximately 28% of female cancers. Several risk factors are known. Not all women exhibiting established risk factors will develop breast cancer but many without recognised risk factors will, indicating involvement of unknown risk factors. Impaired basal or oxidation-stimulated gene expression of redox enzymes, particularly Glutathione Peroxidase 1 and 4 (GPX1 and 4), resulting in increased oxidative stress, could be an "unknown" risk factor in breast cancer. We determined whether basal expression of GPX1 and 4, two major redox enzymes, in Peripheral Blood Mononuclear Cells (PBMNC) and/or their stimulated expression (oxidative stress) was impaired in women with breast cancer who have no known markers of risk compared with control women without breast cancer. A significant 30% impairment (p< 0.01) in basal PBMNC GPX4, but not GPX1, gene expression was observed in cancer patients. Oxidative stress stimulation in vitro did not increase GPX4 expression significantly in cancer patients or control women whereas GPX1 expression was significantly increased (30%, p<0.05) only in the cancer group. Attenuation of GPX4 mRNA expression in PBMNC suggests this could be a simple,early biomarker for future breast cancer risk in the high proportion of women without known risk factors who eventually contract the disease.

The use of FDG-PET in assessing axillary lymph node status in breast cancer: a systematic review and meta-analysis of the literature.

Axillary lymph node status is the most powerful prognostic indicator in patients with breast cancer. FDG-PET has been suggested as a non-invasive method of staging the axilla. The aim of this study was to review and aggregate all studies that measured the performance of FDG-PET in patients with breast cancer, using surgically obtained axillary histology as a reference, in a meta-analysis. A systematic review of the literature was performed and data extracted from all eligible studies. These were then analysed using meta-analysis software and summary receiver operating characteristic (SROC) curves were plotted for the aggregate data. The data was then tested to determine which parameters impacted on the sensitivity and specificity of the studies. Sensitivities ranging from 20 to 100% and specificities ranging from 65 to 100% have been reported. An aggregated ROC analysis found an area under the curve of 0.95 (95% CI 0.91-0.97) and a Q* value of 0.89 (95% CI 0.85-0.92) in a total of 25 studies involving 2,460 patients. The AUC and Q* values indicated little difference between the compared study characteristics. The performance of the technique currently remains below, which is required to replace assessment of axillary node status by surgical biopsy and histological assessment. However, sensitivity and specificity are high and FDG-PET may have a role to play under particular circumstances. Moreover, the additional benefit of an assessment of distal metastatic spread provided by FDG-PET requires further investigation.

Student views on the introduction of anatomy teaching packages into clinical attachments.

Following the implementation of the GMC document Tomorrow's Doctors in 1993 the amount of time dedicated to anatomy in undergraduate curricula has been reduced. This has resulted in considerable disquiet among physicians and surgeons with regard to the anatomical knowledge of newly qualified doctors, and also amongst students. This study aimed to assess the perceived student need for anatomical teaching packages to support clinical attachments in the later years of the undergraduate medical curriculum. The views of two groups of students were obtained: Group A were at the beginning of their clinical attachments, whereas Group B had completed all clinical attachments and had sat the final examination. The majority of students indicated that there was a need for the development of a teaching package for anatomy (and other basic sciences) in the later stages of the undergraduate medical curriculum. A high proportion stated that the completion of these packages should be in a self-directed manner with a staff member available. There was a difference between both groups in response to the best time to offer the packages, and in the clinical areas which might be prioritized in such a development. We conclude that the vertical integration of anatomy--perhaps through clinically focused teaching packages--would be welcomed by students as part of their clinical attachments.

Baseline MRI delivery characteristics predict change in invasive ductal breast carcinoma PET metabolism as a result of primary chemotherapy administration.

BACKGROUND: The aim of the study was to investigate whether pre-therapy vascular delivery assessment [using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)] can predict reduction in breast cancer metabolism [detected using 2-[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography ((18)F(-)FDG-PET)] after a single cycle of chemotherapy. Reduction in (18)F-FDG PET metabolism has previously been shown to correlate with histological response to primary chemotherapy. PATIENTS AND METHODS: Seventeen patients with large or locally advanced invasive ductal carcinomas of the breast were imaged using DCE-MRI and (18)F-FDG-PET prior to therapy and 20 days after the first cycle of chemotherapy. MRI data were analysed using a multi-compartment model. PET data were analysed using standardised uptake value (SUV) analysis. RESULTS: A significant association (P <0.05) was observed between pre-therapy DCE-MRI vascular parameters and the reduction in PET metabolism resulting from administration of one cycle of chemotherapy. CONCLUSIONS: A relationship was demonstrated between pre-therapy DCE-MRI vascular parameters and the reduction in PET metabolism after a single cycle of chemotherapy. This suggests that reduction in PET metabolism as a result of chemotherapy may be dependent, at least in part, on pre-therapy vascular delivery. These pre-therapy vascular characteristics may be suitable for use as a surrogate measure for initial chemotherapy delivery, a key factor in chemotherapeutic efficacy.

A pilot study with long term follow up of hyperbaric oxygen pretreatment in patients with locally advanced breast cancer undergoing neo-adjuvant chemotherapy.

Work in an animal cancer model suggests that pretreatment with hyperbaric oxygen can improve tumor vascularity rendering chemotherapy more effective. Accordingly 32 subjects with locally advanced breast carcinoma (>5cm diameter) entered into a randomized clinical trial where a course was administered of six intravenous pulses of cyclophosphamide 1000mg/m2 i.v., doxorubicin 50mg/m2 i.v. and vincristine 1.5mg/m2 i.v. In the case group this was preceded by ten, once daily, sessions of hyperbaric oxygen therapy (HBO2) administered either at 2.4 or 2.0 atmospheres absolute. Eleven out of 15 subjects tolerated a full course of HBO2 and chemotherapy. All 17 control subjects tolerated a full course of chemotherapy. Tumor extravascular extracellular or edema fluid was reduced after HBO2 but there was no reduction in tumor cell volume and no indication of increased vascularity on MRI. Clinical and pathological responses to chemotherapy were the same in both groups and there was no evidence of neovascularisation. Five year survival in those who tolerated the trial regime was 73% and did not differ between the groups. This mortality was cancer related.

Nutrition and the surgical patient: triumphs and challenges.

The understanding of the role of nutrition in the surgical patient has lead to major developments in the nutritional support of patients undergoing surgery. Reductions in morbidity by ensuring that patients receive optimal nutritional support can be achieved. Furthermore, the use of nutrients to modify immune, inflammatory and metabolic processes also offers new possibilities for reducing morbidity following major surgery. However, we are only at an embryonic stage in our understanding of how nutrients and nutrition affect the genome and this knowledge offers exciting possibilities in the future for modulating many key intracellular processes, particularly in the patient with cancer.

Effect of CLA supplementation on immune function in young healthy volunteers.

OBJECTIVES: This study investigated the effect of dietary CLA supplementation (3g/day; 50:50 mix of the two major isomers) on the immune system and plasma lipids and glucose of healthy human (male and female) volunteers. DESIGN: Double-blind, randomized, reference-controlled study. SUBJECT AND INTERVENTION: A total of 28 healthy male and female participants aged 25-50 y received either high oleic sunflower oil (reference) or 50% CLA 9-11 and 50% CLA 10-12 CLA isomers (50:50 CLA-triglyceride form). The treatments were given as supplements in soft-gel capsules providing a total 3 g (6 x 500 mg capsules) per day in treatment groups for 12 weeks. A 12-week washout period followed the intervention period. RESULTS: Levels of plasma IgA and IgM were increased (P < 0.05 and 0.01 respectively), while plasma IgE levels were decreased (P < 0.05). CLA supplementation also decreased the levels of the proinflammatory cytokines, TNF-alpha and IL-1beta (P < 0.05), but increased the levels of the anti-inflammatory cytokine, IL-10 (P < 0.05). Another aspect of immune function, delayed type hypersensitivity (DTH) response, was decreased during and after CLA supplementation (P < 0.05). However, plasma glucose, lipids, lymphocyte phenotypic results were not affected significantly by CLA. CONCLUSION: This is the first study to show that CLA, a fatty acid naturally found in dairy and meat products, can beneficially affect immune function in healthy human volunteers. SPONSORSHIP: This study was supported by Loders-Croklaan, The Netherlands and SEERAD (Scottish Executive Environmental Rural and Agriculture Department).

Immunonutrition in clinical practice: what is the current evidence?

The clinical trials of immunonutrition that we have undertaken have often been small, single centre studies. They have often been of limited statistical power and have often included patients with a variety of underlying disease states and at different points in the disease process. Three meta-analysis and a consensus statement in conjunction with a systematic review, have been performed in an attempt to overcome many of these limitations and understand further the clinical place for immunonutrition. However, there are still many questions regarding the place of immunonutrition in clinical practice that we still do not understand or have definitive answers to. For example, do we really know what is the optimal combination of nutrients and in what quantities they should be provided? Do we understand any potential interactions that might occur between these nutrients? What is the effect of the patients nutritional state? When and for how long should immunonutrition provided? What is the impact of the patients' underlying disease process and how does this interact with the provision of immunonutrition? At the present time whilst there is some indication and evidence as to which patients might benefit most, and as to those who may not benefit or even suffer detrimental effects from immunonutrition, we still can not answer these questions with any definitive authority. It is essential now that we undertake large well designed, well controlled multicentre studies with adequate statistical power to answer these questions. The indications are that immunonutrition has the potential to help patients but its place must be more clearly defined before its widespread acceptance into clinical practice is based on sound scientific evidence.

Immune suppression and isolated severe head injury: a significant clinical problem.

In the developed world, trauma is the principal cause of death under the age of 40 and is the third largest overall killer. In the UK, approximately 25,000 people die each year as a result of major injury, 25% as a result of head injuries alone. Despite improved diagnosis and management, infection remains the commonest complication in those patients surviving the initial injury. Some 5% are reported to die as a result of septic complications. Prolonged periods of intensive care and respiratory support predispose to infective respiratory complications. These patients in the absence of significant systemic injury and, as a result of severe head injury, are unable to mount an effective immune response. This literature review examines the changes that have been reported to occur in the immune system following isolated severe head injury and explores the relationship these changes may have to the increased development of infective complications.

Breast cancer in women aged 35 and under: prognosis and survival.

BACKGROUND: Breast cancer comprises 22% of all cancers occurring in females but only 2% of cases occur in women aged 35 years and less. The presentation, behaviour and prognosis of breast cancer in such women, when compared with older women, are unclear and conflicting results have been reported. This study has audited clinical and pathological features in patients aged 35 years and under with breast cancer. METHODS: One hundred and thirteen patients were identified. The details of clinical staging, local and distant disease recurrence and overall survival were obtained for all patients. Histological sections of tumours were examined for type, grade, size, presence of surrounding intraductal carcinoma, presence of vascular space invasion, lymph node involvement and oestrogen receptor (ER) status. RESULTS: Histological examination of the tumours revealed that 94% were invasive ductal carcinoma. In 73% of the cases the tumours were grade 3, 49% of patients who underwent axillary surgery had lymph node involvement and 20% of tumours expressed ERs. The overall 5-year survival was 64%. Predictors of a poorer survival (univariate analysis) were: increasing tumour size, absence of ERs, presence of lymphovascular space invasion, axillary lymph node involvement and detectable metastases at the initial presentation. Multivariate analysis revealed that only lymphovascular space invasion was an independent predictor of a poor survival. CONCLUSION: Breast cancer in young (< or = 35 years) women is biologically aggressive, compared with older women. Factors predicting survival and overall survival rates, however, were comparable with those previously reported for older women with breast cancer.