Muscle-Sparing ADM-Assisted Breast Reconstruction Technique Using Complete Breast Implant Coverage: A Dual-Institute UK-Based Experience.

BACKGROUND: We report our early experience of a novel muscle-sparing breast (prepectoral) reconstruction technique using a pre-shaped Braxon® mesh (acellular dermal matrix) which completely wraps around the breast implant. METHODS: All patients who underwent prepectoral implant-based breast reconstruction between April 2014 and September 2015 were included in the analysis. The dermal matrix Braxon® used is a pre-shaped matrix which forms a complete implant mesh wrap. The new breast created is placed over the chest wall without disturbing the pectoralis musculature. RESULTS: A total of 51 (42 unilateral and 9 bilateral) muscle-sparing breast reconstructions were carried out. Complications included implant loss (n = 1; 1.7%) secondary to wound infection, seroma (n = 4; 6.7%), and superficial wound dehiscence (n = 1; 1.7%) which was re-sutured without further complication. The median follow-up period was 16.4 (range 8-25) months. CONCLUSION: The early experience appears highly satisfactory with good clinical outcome. The novel prepectoral implant-based breast reconstruction using the mesh wrap provides an effective alternative to the more traditional submuscular implant-based technique.

Evaluation of a novel breast reconstruction technique using the Braxon® acellular dermal matrix: a new muscle-sparing breast reconstruction.

BACKGROUND: Implant-based breast reconstruction is becoming increasingly popular because of the widespread adoption of acellular dermal matrix (ADM), which allows surgeons to obtain good aesthetic results with fewer operations. To develop more conservative surgical techniques, a retrospective, three-centre, proof-of-concept study was performed to study the effectiveness of a new, immediate, muscle-sparing breast reconstruction technique using the patented Braxon® ADM, which enables subcutaneous positioning of the breast implant without detaching the pectoralis major. METHODS: Ethics committee of the study coordinating centre approved medical record review on 19 women who underwent muscle-sparing breast reconstruction between November 2012 and January 2014. The first 10 implants were performed using 0.9-mm-thick porcine ADM, with preservatives. In the subsequent 15 implants, the product was changed to 0.6-mm-thick porcine dry ADM, without preservatives. RESULTS: Nineteen patients (25 implants) received six bilateral and 13 unilateral muscle-sparing breast reconstructions. For the first type of ADM used (0.9-mm-thick with preservatives), the rate of implant loss was 12% (n = 3) because of seroma (8%, n = 2) and infection (4%, n = 1). Minor complications, such as seroma (8%, n = 2), occurred when using the 0.6-mm-thick Braxon® ADM and were treated by aspiration. Symmetrical and natural breasts with good shape, ptosis and softness to the touch were obtained. None of the patients reported experiencing pain. CONCLUSIONS: The preliminary results are encouraging from aesthetic and clinical viewpoints. Further studies are planned to evaluate long-term results.

The impact of the 21-gene assay on adjuvant treatment decisions in oestrogen receptor-positive early breast cancer: a prospective study.

BACKGROUND: International guidelines, including NICE, recommend using the 21-gene Recurrence Score assay for guiding adjuvant treatment decisions in ER+, HER2-negative early breast cancer (BC). We investigated the impact of adding this assay to standard pathological tests on clinicians'/patients' treatment decisions and on patients' decisional conflict in the United Kingdom. METHODS: In this prospective multicentre study, eligibility criteria included: ER+ HER2-negative BC (N0/Nmic for patients ⩽50 years; ⩽3 positive lymph nodes for patients >50 years) and being fit for chemotherapy. Physicians'/patients' treatment choices and patients' decisional conflict were recorded pre- and post testing. RESULTS: The analysis included 137 patients. Overall, adjuvant treatment recommendations changed in 40.7% of patients, with the direction of the change consistent with the Recurrence Score results (net decrease in chemotherapy recommendation rate in low Recurrence Score patients and net increase in high Recurrence Score patients). Patients' choices were generally consistent with physicians' recommendations. Post-testing, patients' decisional conflict decreased significantly (P<0.0001). In the 67 patients meeting the NICE criteria for testing, the recommendation change rate was 49.3%. CONCLUSIONS: Recurrence Score testing significantly influenced treatment recommendations overall and in the subgroup of patients meeting the NICE criteria, suggesting that this test could substantially alter treatment patterns in the United Kingdom.

Time to be BRAVE: is educating surgeons the key to unlocking the potential of randomised clinical trials in surgery? A qualitative study.

BACKGROUND: Well-designed randomised clinical trials (RCTs) provide the best evidence to inform decision-making and should be the default option for evaluating surgical procedures. Such trials can be challenging, and surgeons' preferences may influence whether trials are initiated and successfully conducted and their results accepted. Preferences are particularly problematic when surgeons' views play a key role in procedure selection and patient eligibility. The bases of such preferences have rarely been explored. Our aim in this qualitative study was to investigate surgeons' preferences regarding the feasibility of surgical RCTs and their understanding of study design issues using breast reconstruction surgery as a case study. METHODS: Semistructured qualitative interviews were undertaken with a purposive sample of 35 professionals practicing at 15 centres across the United Kingdom. Interviews were transcribed verbatim and analysed thematically using constant comparative techniques. Sampling, data collection and analysis were conducted concurrently and iteratively until data saturation was achieved. RESULTS: Surgeons often struggle with the concept of equipoise. We found that if surgeons did not feel 'in equipoise', they did not accept randomisation as a method of treatment allocation. The underlying reasons for limited equipoise were limited appreciation of the methodological weaknesses of data derived from nonrandomised studies and little understanding of pragmatic trial design. Their belief in the value of RCTs for generating high-quality data to change or inform practice was not widely held. CONCLUSION: There is a need to help surgeons understand evidence, equipoise and bias. Current National Institute of Health Research/Medical Research Council investment into education and infrastructure for RCTs, combined with strong leadership, may begin to address these issues or more specific interventions may be required.

Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study.

The adjuvant use of aromatase inhibitors in breast cancer is associated with adverse effects on bone health. We previously reported a decline in bone mineral density (BMD) following the switch from tamoxifen to exemestane in the Intergroup Exemestane Study (IES). Here we report effects of endocrine treatment withdrawal on BMD, bone turnover markers (BTM) and fracture rates. 4,724 patients took part in IES, and 206 patients were included in a bone sub-study. BMD and BTM were assessed pre-randomization, during and after the end of treatment (EOT). To evaluate treatment withdrawal effects, 12- and 24-month post EOT BMD results are available for 122 and 126 patients, respectively. Similar patient numbers had BTM measured post EOT. Following treatment withdrawal, the differences in BMD observed between the two endocrine strategies were partially reversed. At 24 months from EOT, spine BMD increased by 1.53% (95%CI 0.63-2.43; p = 0.001) after stopping exemestane and fell by 1.93% (95%CI -2.91 to 0.95; p = 0.0002) following tamoxifen withdrawal. A similar pattern of changes was observed at the hip. At 2 years post EOT, BMD changes from baseline were similar with both treatment strategies. Corresponding inverse changes in BTM were seen, with an increase following tamoxifen withdrawal and a reduction after exemestane. A higher number of fractures occurred during exemestane treatment, but fracture rates were similar after treatment withdrawal. With the switch strategy used in IES, the on treatment adverse bone effects of exemestane are reversed. Ongoing monitoring of BMD is therefore not routinely required.

Referral patterns, cancer diagnoses, and waiting times after introduction of two week wait rule for breast cancer: prospective cohort study.

OBJECTIVE: To investigate the long term impact of the two week wait rule for breast cancer on referral patterns, cancer diagnoses, and waiting times. DESIGN: Prospective cohort study. SETTING: A specialist breast clinic in a teaching hospital in Bristol. PARTICIPANTS: All patients referred to breast clinic from primary care between 1999 and 2005. MAIN OUTCOME MEASURES: Number, route, and outcome of referrals from primary care and waiting times for urgent and routine appointments. RESULTS: The annual number of referrals increased by 9% over the seven years from 3499 in 1999 to 3821 in 2005. Routine referrals decreased by 24% (from 1748 to 1331), but two week wait referrals increased by 42% (from 1751 to 2490) during this time. The percentage of patients diagnosed with cancer in the two week wait group decreased from 12.8% (224/1751) in 1999 to 7.7% (191/2490) in 2005 (P<0.001), while the number of cancers detected in the "routine" group increased from 2.5% (43/1748) to 5.3% (70/1331) (P<0.001) over the same period. About 27% (70/261) of people with cancer are currently referred in the non-urgent group. Waiting times for routine referrals have increased with time. CONCLUSION: The two week wait rule for breast cancer is failing patients. The number of cancers detected in the two week wait population is decreasing, and an unacceptable proportion is now being referred via the routine route. If breast cancer services are to be improved, the two week wait rule should be reviewed urgently.

Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study.

BACKGROUND: Tamoxifen preserves bone in postmenopausal women, but non-steroidal aromatase inhibitors accelerate bone loss and increase fracture risk. We aimed to study the effect on bone health in a subgroup of women included in the Intergroup Exemestane Study (IES), a large randomised trial that compared the switch to the steroidal aromatase inhibitor exemestane with continuation of tamoxifen in the adjuvant treatment of postmenopausal breast cancer. METHODS: Results were analysed from 206 evaluable patients from the IES, in which postmenopausal women with histologically confirmed and completely resected unilateral breast cancer (that was oestrogen-receptor positive or of unknown status), who were disease-free after 2-3 years of treatment with tamoxifen were randomised to continue oral tamoxifen 20 mg/day or switch to oral exemestane 25 mg/day to complete a total of 5 years of adjuvant endocrine therapy. The primary endpoint was change in bone-mineral density (BMD) assessed by dual energy X-ray absorptiometry. Changes in biochemical markers of bone turnover were also analysed in this substudy, and the incidence of fractures in the entire study reported. The IES is registered on the Current Controlled Trials website . FINDINGS: Within 6 months of switching to exemestane, BMD was lowered by 0.051 g/cm(3) (2.7%; 95% CI 2.0-3.4; p<0.0001) at the lumbar spine and 0.025 g/cm(3) (1.4%; 0.8-1.9; p<0.0001) at the hip compared with baseline. BMD decreases were only 1.0% (0.4-1.7; p=0.002) and 0.8% (0.3-1.4; p=0.003) in year 2 at the lumbar spine and hip, respectively. No patient with BMD in the normal range at trial entry developed osteoporosis. Bone resorption and formation markers increased at all time points in women receiving exemestane (p<0.001). With a median follow-up in all IES participants (n=4274) of 58 months, 162 (7%) and 115 (5%) patients in the exemestane and tamoxifen groups, respectively, had fractures (odds ratio 1.45 [1.13-1.87]; p=0.003). INTERPRETATION: These results indicate that the increase in survival shown previously with the IES switch strategy is achieved at the expense of some detriment to skeletal health, so the risk-benefit ratio to women needs to be individually assessed.

The psychological effect of mastectomy with or without breast reconstruction: a prospective, multicenter study.

A multicenter, prospective study ( = 103) examined the psychological implications of women's decisions for or against breast reconstruction. Recognized measures of anxiety, depression, body image, and quality of life were completed before the operation, and 6 and 12 months later. A reduction in psychological distress over the year following the operation was evident in each surgical group (mastectomy alone or immediate or delayed reconstruction), indicating that reconstructive surgery can offer psychological benefits to some women; however, others report improved psychological functioning without this surgical procedure. In contrast to existing retrospective research, the prospective design enabled the process of adjustment during the first year after the operation to be examined. The results indicate that breast reconstruction is not a universal panacea for the emotional and psychological consequences of mastectomy. Women still reported feeling conscious of altered body image 1 year postoperatively, regardless of whether or not they had elected breast reconstruction. Health professionals should be careful of assuming that breast reconstruction necessarily confers psychological benefits compared with mastectomy alone.