Identification of factors that influence the decision to take chemoprevention in patients with a significant family history of breast cancer: results from a patient questionnaire survey.

PURPOSE: Chemoprevention reduces the risk of developing breast cancer in women with increased family history (FH) risk of breast cancer. However, chemoprevention uptake remains low and the reasons for this remain unclear. METHODS: Patients with moderate- or high-risk FH of breast cancer were counselled about chemoprevention (n = 1620; September 2015 to July 2018) in breast clinics. A postal questionnaire survey was subsequently sent to these patients in order to explore the potential factors influencing their decision on chemoprevention uptake. RESULTS: 518 patients (32%) completed the questionnaire survey; 75% were pre-menopausal and the majority had moderate as opposed to high-risk FH (87.5% vs. 12.5%). Breast cancer chemoprevention uptake rate was 10.8% (56/518). The identified incentives were more commonly stated for patients who took chemoprevention when compared to those who refused chemoprevention. The commonest incentives were breast cancer prevention (89.3% vs. 61.7%; p = 0.001), belief in the effectiveness of chemoprevention (76.8% vs. 63.4%; p = 0.048), and personal perception of breast cancer risk (67.9% vs. 45.5%; p = 0.002). Similarly, the identified barriers were more commonly stated for patients who refused chemoprevention when compared to those who took chemoprevention. The commonest barriers were side effects (79.4% vs. 55.4%; p = 0.001) and lack of information (53% vs. 28.6%; p = 0.001). CONCLUSION: Despite its proven efficacy, chemoprevention uptake in patients with a significant FH of breast cancer remains low. We have identified important factors which influence the patient's decision making. Future clinic consultations should focus on exploring these factors to aid patient decision making.

An observational study on the expression levels of MDM2 and MDMX proteins, and associated effects on P53 in a series of human liposarcomas.

BACKGROUND: Inactivation of wild type P53 by its main cellular inhibitors (MDM2 and MDMX) is a well recognised feature of tumour formation in liposarcomas. MDM2 over-expression has been detected in approximately 80% of liposarcomas but only limited information is available about MDMX over-expression. To date, we are not aware of any study that has described the patterns of MDM2 and MDMX co-expression in liposarcomas. Such information has become more pertinent as various novel MDM2 and/or MDMX single and dual affinity antagonist compounds are emerging as an alternative approach for potential targeted therapeutic strategies. METHODS: We analysed a case series of 61 fully characterized liposarcomas of various sub-types by immunohistochemistry, to assess the expression levels of P53, MDM2 and MDMX, simultaneously. P53 sequencing was performed in all cases that expressed P53 protein in 10% or more of cells to rule out mutation-related over-expression. RESULTS: 50 cases over-expressed MDM2 and 42 of these co-expressed MDMX at varying relative levels. The relative expression levels of the two proteins with respect to each other were subtype-dependent. This apparently affected the detected levels of P53 directly in two distinct patterns. Diminished levels of P53 were observed when MDM2 was significantly higher in relation to MDMX, suggesting a dominant role for MDM2 in the degradation of P53. Higher levels of P53 were noted with increasing MDMX levels suggesting an interaction between MDM2 and MDMX that resulted in a reduced efficiency of MDM2 in degrading P53. Of the 26 cases of liposarcoma with elevated P53 expression, 5 were found to have a somatic mutation in the P53 gene. CONCLUSIONS: The results suggest that complex dynamic interactions between MDM2 and MDMX proteins may directly affect the cellular levels of P53. This therefore suggests that careful characterization of both these markers will be necessary in tumours when considering in vivo evaluation of novel blocker compounds for MDM proteins, as a therapeutic strategy to restore wild type P53 function.

Lumbar herniation following extended autologous latissimus dorsi breast reconstruction.

BACKGROUND: Reconstructive breast surgery is now recognized to be an important part of the treatment for breast cancer. Surgical reconstruction options consist of implants, autologous tissue transfer or a combination of the two. The latissimus dorsi flap is a pedicled musculocutaneous flap and is an established method of autologous breast reconstruction.Lumbar hernias are an unusual type of hernia, the majority occurring after surgery or trauma in this area. The reported incidence of a lumbar hernia subsequent to a latissimus dorsi reconstruction is very low. CASE PRESENTATION: We present the unusual case of lumbar herniation after an extended autologous latissimus dorsi flap for breast reconstruction following a mastectomy. The lumbar hernia was confirmed on CT scanning and the patient underwent an open mesh repair of the hernia through the previous latissimus dorsi scar. CONCLUSION: Lumbar hernias are a rare complication that can occur following latissimus dorsi breast reconstruction. It should be considered in all patients presenting with persistent pain or swelling in the lumbar region.

Perioperative reductions in circulating lymphocyte levels predict wound complications after excisional breast cancer surgery.

OBJECTIVE: Postoperative wound complications after excisional surgery for primary breast cancer can result in patients requiring additional treatments and delay adjuvant therapy and are associated with worse prognoses.We investigated factors that might predispose patients to wound complications. BACKGROUND: A number of patient characteristics have been associated with wound complications, but there is currently no quantitative measure of the risk of their occurrence. Our hypothesis was that wound complications are related, in part, to the immune status of patients. METHODS: We recruited patients undergoing surgery for primary breast cancer and determined their circulating levels of various immune cells shortly before and after surgery as a measure of immune status. RESULTS: One hundred seventeen patients were recruited; 16 (13.7%) developed wound complications. The following patient and tumor characteristics were associated with higher wound complication rates: diabetes (P = 0.02); larger tumors (T2/3 vs T1; P = 0.02); metastatic axillary nodes (P = 0.006). With respect to immune status, no significant differences in preoperative levels of circulating immune cells were detected between patients who developed wound complications and those who did not. However, patients who developed complications showed greater reductions in lymphocyte levels 4 hours postoperatively than those who did not (P <0.001). Multivariate analyses demonstrated that falls in lymphocyte levels of greater than 20% or 50% 4 hours postoperatively acted as a significant and independent predictor of wound complications (P < 0.005 and P < 0.0001,respectively). CONCLUSIONS: Perioperative changes in lymphocyte levels could provide a practical predictive marker for wound complications on which selective antibiotic prophylaxis could be based.

Audit of routine preoperative blood test requests for patients undergoing elective breast surgery: Less is more.

In 2016, the National Institute for Health and Care Excellence updated guidelines on preoperative blood tests for elective surgery; with failure of adherence having implications for both patients and healthcare providers. A local audit was performed on 919 patients undergoing elective breast surgery that determined compliance and the financial implications of performing inappropriate preoperative blood tests against the National Institute for Health and Care Excellence guideline. Initial findings of an unacceptable quantity of inappropriate blood tests led to the education of the pre-assessment clinic staff regarding the guidelines along with the development of a poster to guide the ordering of appropriate tests. A re-audit of 451 patients assessed impact of interventions which resulted in a significant reduction in the number of blood tests requested with a 71% reduction in financial expenditure. The blood tests considered inappropriate in both the initial and re-audit did not add any relevant clinical information and abnormal results did not alter the clinical course of the patient.

Analysis of Secondary Surgeries after Immediate Breast Reconstruction for Cancer Compared with Risk Reduction.

This study sets out to compare reconstructive practice between patients undergoing immediate breast reconstruction (IBR) for cancer and those who opted for risk reduction (RR), with an emphasis on examining patterns of secondary surgery. METHODS: Data collection was performed for patients undergoing mastectomy and IBR at a teaching hospital breast unit (2013-2016). RESULTS: In total, 299 patients underwent IBR (76% cancer versus 24% RR). Implant-based IBR rate was similar in both groups (58% cancer versus 63% RR). Reconstruction loss (5.3% cancer versus 4.2% RR) and complication (16% cancer versus 12.9% RR) rates were similar. Cancer patients were more likely to undergo secondary surgery (68.4% versus 56.3%; P = 0.025), including contralateral symmetrization (22.8% versus 0%) and conversion to autologous reconstruction (5.7% versus 1.4%). Secondary surgeries were mostly planned for cancer patients (72% planned versus 28% unplanned), with rates unaffected by adjuvant therapies. This distribution was different in RR patients (51.3% planned versus 48.7% unplanned). The commonest secondary procedure was lipomodeling (19.7% cancer versus 23.9% RR). For cancer patients, complications resulted in a significantly higher unplanned secondary surgery rate (82.5% versus 38.8%; P = 0.001) than patients without complications. This was not evident in the RR patients, where complications did not lead to a significantly higher unplanned surgery rate (58.9% versus 35.2%; P = 0.086). CONCLUSIONS: Most of the secondary surgeries were planned for cancer patients. However, complications led to a significantly higher rate of unplanned secondary surgery. Approximately 1 in 4 RR patients received unplanned secondary surgery, which may be driven by the desire to achieve an optimal aesthetic outcome.

Management of breast cancer in an Asian man with post-traumatic stress disorder: a case report.

BACKGROUND: Migration to the UK has increased considerably, which is reflected in the diverse multicultural population which includes asylum seekers and economic migrants. Differences in ethnic and cultural values between the host and newcomer populations could impact on effective health care provision, especially in gender-biased conditions such as breast cancer. Breast cancer is rare in men and the diagnosis is often met with disbelief. This case report describes an unusual case of breast cancer in an Afghan man who is an asylum seeker of Asian ethnic origin. CASE PRESENTATION: A focused ethnographic case study and in-depth interview was used to gain qualitative data and insight into the personal experiences of a male Afghan asylum seeker, age unknown (estimated to be in his 30s), with post-traumatic stress disorder who was electively admitted into hospital for the investigation of a suspicious lump in his left breast, which was subsequently found to be breast cancer. He was extremely reluctant to accept a breast cancer diagnosis and initially would not consent to any treatment, preferring to seek further opinion. During consultation with various members of the breast team he continually declined to accept the diagnosis and felt there was an error in the investigative protocol. Through the involvement of a Muslim nurse, fluent in Urdu and knowledgeable of the Afghan culture and religious background, we learned about his experiences and feelings; he opened up to her about his experiences in Afghanistan, detailing his experiences of trauma as a result of war, and disclosing that he had been diagnosed as having post-traumatic stress disorder by his physician. He saw breast cancer as a "woman's disease" which deeply affected his feelings of masculinity and left him feeling vulnerable. CONCLUSIONS: While sensitivity is undoubtedly required when diagnosing gender-biased conditions such as breast cancer in men, our experience showed this is exacerbated in ethnic minority groups where language barriers often exist and awareness of cultural differences is required. Awareness of the possibility of post-traumatic stress disorder in migrant populations from conflict-torn areas is also recommended during consultation.

The TeaM (Therapeutic Mammaplasty) study: Protocol for a prospective multi-centre cohort study to evaluate the practice and outcomes of therapeutic mammaplasty.

INTRODUCTION: Wide local excision and adjuvant radiotherapy is the standard of care for early breast cancer. For large tumours, however, mastectomy is frequently recommended as conventional breast-conserving techniques often result in poor cosmetic outcomes. Therapeutic mammaplasty (TM) may extend the boundaries of breast-conserving surgery by combining breast reduction and mastopexy techniques with tumour excision, preserving a natural breast shape and avoiding the need for mastectomy. The prevalence of this operative option among surgeons in the UK and its success rate are unknown. The TeaM study is a multicentre prospective study that aims to investigate the practice and outcomes of TM. METHODS AND ANALYSIS: Breast centres performing TM will be invited to participate through the research collaborative network and the professional associations. All patients undergoing TM between September 2016 and March 2017 will be included. Demographic, operative, oncological and complication data within 30-days of surgery will be collected. The primary outcome will be unplanned re-operation for complications. Secondary outcomes will include unplanned readmission, re-excision rates and time to adjuvant therapy. Prospective data on 500 patients from 50 centres are anticipated. Exploratory analyses will identify predictors for complications and inform the design of a definitive study. ETHICS AND DISSEMINATION: Research ethics approval is not required for this study. This has been confirmed by the on-line Health Research Authority decision tool. This study will provide novel information regarding the practice and outcomes of TM in the UK. This will inform decision-making for patients and surgeons and inform future research. Dissemination of the study protocol will be via the Mammary Fold Academic and Research Collaborative, the Reconstructive Surgery Trials Network and the professional associations, the Association of Breast Surgery and British Association of Plastic, Reconstructive and Aesthetic Surgeons. Results will be presented at relevant surgical conferences and published in peer-reviewed journals.

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders.

BACKGROUND: Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. METHODS: Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). RESULTS: A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. CONCLUSIONS: This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts.

Solitary subcutaneous metastatic deposit from hepatocellular carcinoma.

Hepatocellular carcinoma is the most common primary tumour of the liver. Metastasis is frequent in these aggressive tumours and is commonly to the lungs, regional lymph nodes, or bone. Metastasis as a discrete subcutaneous nodule has not been described before. We report a case of hepatocellular carcinoma with a solitary subcutaneous metastatic deposit identified 18 months after the initial hepatic surgery.