Lester Barr

Randomised controlled trial of effects of early discharge after surgery for breast cancer

Abstract Objective : To determine the effect of early discharge from hospital after surgery for breast cancer on physical and psychological illness. Design : Randomised controlled trial comparing discharge two days after surgery (before removal of drain) with standard management (discharge after removal of drain). Setting : Regional breast unit. Subjects : 100 women with early breast cancer undergoing mastectomy and axillary node clearance (20) or breast conservation surgery (80). Main outcome measures : Physical illness (infection, seroma formation, shoulder movement) and psychological illness (checklist of concerns, Rotterdam symptom questionnaire, hospital anxiety and depression scale) preoperatively and at one month and three months postoperatively. Results : Women discharged early had greater shoulder movement (odds ratio 0.28 (95% confidence interval 0.08 to 0.95); P=0.042) and less wound pain (odds ratio 0.28 (0.10 to 0.79); P=0.016) three months after surgery compared with women given standard management. One month after surgery scores were significantly lower on the Rotterdam symptom questionnaire in patients who were discharged early (ratio of geometric mean scores 0.73 (0.55 to 0.98); P=0.035), but rates of psychological illness generally did not differ between groups. Conclusions : Increased rates of physical or psychological illness did not result from early discharge after surgery for breast cancer. This policy can be recommended for patients with support at home.

Extent of excision margin width required in breast conserving surgery for ductal carcinoma in situ

Breast conserving surgery (BCS) is common practice for unifocal ductal carcinoma in situ (DCIS) less than 4 cm in size, but the extent of tumor free margin width around DCIS necessary to minimize recurrence is unclear.

Late Toxicity Is Not Increased in BRCA1/BRCA2 Mutation Carriers Undergoing Breast Radiotherapy in the United Kingdom

Purpose: To undertake the first substantial clinical study of breast radiotherapy toxicity in BRCA1 and BRCA2 mutation carriers in the United Kingdom. Experimental Design: Acute and late radiation effects were evaluated in a retrospective study of 55 BRCA1 and BRCA2 mutation carriers treated with radiotherapy for breast cancer at four centers between 1983 and 2002. Individual matching with controls who had sporadic breast cancer was undertaken for age at diagnosis, time since completion of radiation, and treatment variables. Detailed assessments were undertaken by one examiner. Median follow-up was 6.75 years for carriers and 7.75 years for controls. Rates of late events (rib fractures, lung fibrosis, necrosis of soft tissue/bone, and pericarditis) as well as LENT-SOMA scores and clinical photography scores of breast size, shape, and skin telangiectasia were the primary end points. Results: No increase in clinically significant late toxicity was seen in the mutation carriers. Conclusions: These data add substantial weight to the evidence that the outcomes in the treated breast from radiotherapy in women with BRCA1 or BRCA2 mutations are comparable with those in women with sporadic breast cancer.

Cyclooxygenase-2 inhibition does not improve the reduction in ductal carcinoma in situ proliferation with aromatase inhibitor therapy: Results of the ERISAC randomized placebo-controlled trial

Purpose: Tamoxifen reduces risk of recurrence after breast conservation surgery for ductal carcinoma in situ (DCIS), but no data exists on the effectiveness of aromatase inhibitors for DCIS. Cyclooxygenase-2 (COX-2) is overexpressed in DCIS, representing another potential therapeutic target. The aim of the study was to determine the effect of aromatase and/or COX-2 inhibition on epithelial proliferation and apoptosis in a presurgical study of estrogen receptor (ER)–positive DCIS. Methods: Postmenopausal women with ER-positive DCIS diagnosed by core biopsy were randomized to a 2 × 2 design of either 14 days of exemestane or placebo and celecoxib, or placebo immediately before surgery. Paired baseline and end point biopsies were analyzed for proliferation (Ki67), apoptosis, human epidermal growth factor receptor 2 (HER2), COX-2, and progesterone receptor (PR) expression by immunohistochemistry. The primary end point was a decrease in Ki67 between diagnosis and surgical excision. Results: Ninety women were randomized: all were ER positive, 49 (54%) had grade III tumors, and 29 (32%) were HER2 positive (3+). Exemestane reduced proliferation compared with placebo with a median reduction of 9% (95% confidence interval, 6-14; P < 0.001). Progesterone receptor was reduced by exemestane (mean decrease, 19%; 95% confidence interval, 9-28; P = 0.011). The effect of exemestane on proliferation was seen regardless of grade, HER2, or PR expression. Celecoxib had no effect on proliferation or apoptosis alone, or in combination with exemestane. Conclusions: Exemestane reduces proliferation in ER-positive DCIS. Aromatase inhibition is a potential alternative to tamoxifen in patients who have undergone breast conservation for ER-positive DCIS. Clin Cancer Res; 16(5); 1605–12

Cost minimisation analysis of using acellular dermal matrix (Strattice™) for breast reconstruction compared with standard techniques.

BACKGROUND We performed a cost analysis (using UK 2011/12 NHS tariffs as a proxy for cost) comparing immediate breast reconstruction using the new one-stage technique of acellular dermal matrix (Strattice™) with implant versus the standard alternative techniques of tissue expander (TE)/implant as a two-stage procedure and latissimus dorsi (LD) flap reconstruction. METHODS Clinical report data were collected for operative time, length of stay, outpatient procedures, and number of elective and emergency admissions in our first consecutive 24 patients undergoing one-stage Strattice reconstruction. Total cost to the NHS based on tariff, assuming top-up payments to cover Strattice acquisition costs, was assessed and compared to the two historical control groups matched on key variables. RESULTS Eleven patients having unilateral Strattice reconstruction were compared to 10 having TE/implant reconstruction and 10 having LD flap and implant reconstruction. Thirteen patients having bilateral Strattice reconstruction were compared to 12 having bilateral TE/implant reconstruction. Total costs were: unilateral Strattice, £3685; unilateral TE, £4985; unilateral LD and implant, £6321; bilateral TE, £5478; and bilateral Strattice, £6771. CONCLUSIONS The cost analysis shows a financial advantage of using acellular dermal matrix (Strattice) in unilateral breast reconstruction versus alternative procedures. The reimbursement system in England (Payment by Results) is based on disease-related groups similar to that of many countries across Europe and tariffs are based on reported hospital costs, making this analysis of relevance in other countries.

Acute chemotherapy-related toxicity is not increased in BRCA1 and BRCA2 mutation carriers treated for breast cancer in the United Kingdom

Purpose: To evaluate acute toxicity induced by chemotherapy for breast cancer in a retrospective study of 62 BRCA1/2 mutation carriers matched 1:1 with women who had treatment for sporadic disease in the United Kingdom between 1983 and 2003. Experimental Design: All participants were interviewed by one of two researchers using standardized questionnaires, and their medical records were reviewed by one research nurse. The two main regimens received were cyclophosphamide, methotrexate, and fluorouracil and fluorouracil, epirubicin, and cyclophosphamide. The proportion of cases and controls receiving anthracycline-based treatment was equivalent, but fewer BRCA1 cases received this treatment than did BRCA2 mutation carriers. Toxicity was documented using the Eastern Cooperative Oncology Group Common Toxicity Criteria for hematologic, infective, and gastrointestinal toxicities. No increase in toxicity was seen in BRCA1/2 mutation carriers. Results: The only significant difference was that neutropenia was less evident in BRCA2 mutation carriers than in either BRCA1 mutation carriers or controls. As a result, there was no requirement for dose reduction among BRCA2 mutation carriers, in contrast to 10 of 39 BRCA1 carriers and 16 of 62 controls (P = 0.02). Conclusions: This result has implications for therapy and indicates that women with mutations in BRCA1 and BRCA2 may be given the same doses of chemotherapy as noncarriers.

Using the Internet for information about breast cancer: a questionnaire-based study.

OBJECTIVES To identify the proportion of breast cancer patients that used the Internet for breast cancer information; to classify patterns of use based on patient demographics; and to evaluate whether using the Internet for this purpose was beneficial or problematic. Also to recognize whether a specific demographic group was more likely to experience problems when using the Internet for breast cancer information. METHODS A 10-item questionnaire was given to patients who attended the breast unit at the University Hospital of South Manchester between May and June 2011 following breast cancer treatment within the last 5 years. RESULTS 200 questionnaires were completed. 50.5% of patients had used the Internet for breast cancer information, with younger (p<0.001) patients with a higher household income (p<0.001) being most likely to do so. The majority (73%) found it beneficial; however 31% had experienced problems. Ethnicity affected the likelihood of experiencing problems with white patients encountering fewer problems (25%) than non-white patients (64%) (p=0.008). CONCLUSION A significant proportion of breast cancer patients will encounter difficulties when using the Internet for breast cancer information, particularly those from ethnic minorities. PRACTICE IMPLICATIONS Health professionals need to include a discussion about Internet use in consultations with breast cancer patients.

The Manchester guidelines for contralateral risk-reducing mastectomy.

BackgroundRates of contralateral risk-reducing mastectomy (CRRM) are rising, despite a decreasing global incidence of contralateral breast cancer. Reasons for requesting this procedure are complex, and we have previously shown a variable practice amongst breast and plastic surgeons in England. We propose a protocol, based on a published systematic review, a national UK survey and the Manchester experience of CRRM.MethodsWe reviewed the literature for risk factors for contralateral breast cancer and have devised a 5-step process that includes history taking, calculating contralateral breast cancer risk, cooling off period/counselling, multi-disciplinary assessment and consent. Members of the multi-disciplinary team included the breast surgeon, plastic surgeon and geneticist, who formulated guidelines.ResultsA simple formula to calculate the life-time risk of contralateral breast cancer has been devised. This allows stratification of breast cancer patients into different risk-groups: low, above average, moderate and high risk. Recommendations vary according to different risk groups.ConclusionThese guidelines are a useful tool for clinicians counselling women requesting CRRM. Risk assessment is mandatory in this group of patients, and our formula allows evidence-based recommendations to be made.

Bioprosthetics: changing the landscape for breast reconstruction?

Approximately 20% of the 17 000 women undergoing mastectomy annually in the UK proceed with immediate breast reconstruction. The commonest type of reconstruction is the two stage Tissue Expander/Implant based operation (37%) followed by use of pedicled myocutaneous flaps either autologous (27%) or with implant (22%). Difficulties with implant based reconstructions such as capsular contraction or malposition are well documented. Pedicled myocutaneous flaps are popular and versatile techniques for breast reconstruction but patients can suffer functional deficits and donor site morbidity. These issues have promoted the development and use of bioprosthetics, namely acellular dermal matrices (ADM), in breast reconstruction. Originally derived from human cadevaric dermis these biological allografts were used for reconstruction following extensive burns, soft tissue defects and large ventral hernias. Their use in breast reconstruction cases has been rising in the USA and more recently in Europe. To render ADMs suitable for human use cells within the donor skin containing or presenting major histocompatibility complex antigens (keratinocytes, Langerhans’ cells and melanocytes within the epidermis, dendritic cells and endothelial cells of the dermis) have to be removed whilst leaving behind the dermal matrix components such as collagen fibres, elastin and proteoglycans. Once implanted, histological studies of human ADMs show that within seven days of being placed in vivo there is active host myofibroblast and endothelial cell infiltration into the graft dermal matrix with development of large numbers of microvessels. The complexity of supply of human cadaveric skin, limitations due to size and consistency of harvested tissue and the risk of disease transmission has led to the development of ADM derived from porcine skin such as Permacol (Covidien, Boulder, CO) and Strattice (LifeCell), the latter having a licence for use in the UK. Collagen fibre arrangement and dermal structure are similar in human and porcine dermis though in the latter the collagen fibres are more densely packed and contain less elastin which may contribute to reduced fibroblast infiltration seen in vivo when compared to human derivedADM.Humans have a cellular and humoral immune response to the immunogenic epitope galactosea-1,3-galactose contained within porcine dermis. Removal

Attitudes to contralateral risk reducing mastectomy among breast and plastic surgeons in England

INTRODUCTION Rates of contralateral risk reducing mastectomy (CRRM) are rising despite a paucity of data to support this practice. Surgeons work as part of the multidisciplinary team (MDT). They may counsel women on these requests without the benefit of established guidelines or agreed protocol. This study assessed the practices and perceptions of breast and plastic surgeons in England on CRRM. METHODS A postal questionnaire was sent to 455 breast and 364 plastic surgeons practising in England. Basic demographics, trends in CRRM, risk assessment, role of the MDT and knowledge base were assessed. RESULTS The response rate among breast surgeons was 48.3% (220/455) and 12.6% (46/364) among plastic surgeons. Nearly half (44%) of the respondents felt there had been an increase in rates of CRRM over the last three years. Seventy-one per cent of those surveyed performed 1-5 CRRMs annually while sixteen per cent did not perform this procedure at all. A third (32%) of respondents correctly quoted their patients an annual risk of 0.5-0.7%. Funding was refused in 4% of cases and 43% of the surgeons felt that in the future they would have to apply to relevant clinical commissioning groups. Over half (58%) of all respondents reported that decisions for CRRM are always discussed in the MDT meeting but 6% stated that these cases are never discussed by the MDT. BRCA mutation was perceived as the main risk factor for contralateral breast cancer by 81% of respondents. Surgeons felt that women requested CRRM mainly to alleviate anxiety. The next most common reasons were carriage of BRCA mutation and a desire to have reconstructions match. CONCLUSIONS A wide variation of surgical practices and perceptions exist in assessing women for CRRM. Guidelines to standardise practices are required.