Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial.

BACKGROUND: Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period. METHODS: IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer. FINDINGS: 3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105-156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0·51, 95% CI 0·39-0·66, p<0·0001). The reduction was larger in the first 5 years (35 vs 89, 0·39, 0·27-0·58, p<0·0001), but still significant after 5 years (50 vs 76 new cases, 0·64, 0·45-0·91, p=0·014), and not significantly different from the first 5 years (p=0·087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0·46, 95% CI 0·33-0·65, p<0·0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0·41, 0·22-0·79, p=0·0081), especially in participants known to be oestrogen receptor-positive (0·22, 0·78-0·65, p<0·0001). No significant difference in deaths was observed overall (69 vs 70, HR 0·96, 95% CI 0·69-1·34, p=0·82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0·72, 95% CI 0·57-0·91, p=0·0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed. INTERPRETATION: This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality. FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, Sanofi Aventis, and AstraZeneca.

Prepectoral implant-based breast reconstruction: a joint consensus guide from UK, European and USA breast and plastic reconstructive surgeons.

Advances in implantable biologic and synthetic products over the last decade have enabled surgeons to replace traditional submuscular implant-based breast reconstruction techniques with a prepectoral or muscle-sparing technique. Prepectoral breast reconstruction is becoming increasingly popular among surgeons and patients due to the preservation of normal chest wall anatomy, with the restoration of body image with minimal morbidity. In this article, we have described a guide to prepectoral or muscle-sparing breast reconstruction with a particular emphasis on patient selection, technique and postoperative outcomes. Hence, a joint consensus guide from European and USA breast and plastic reconstructive surgeons has been agreed, and a crowd-writing method has been adopted to produce this guide.

Correction to: Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome Correlations.

The article "Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome Correlations", written by Barbara Schwartzberg et al., was originally published electronically on the publisher's internet portal (currently SpringerLink) on July 9, 2018, without open access.

Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome Correlations.

BACKGROUND: An institutional review board-approved, multicenter clinical trial was designed to determine the efficacy and outcome of percutaneous laser ablation (PLA) in the treatment of invasive ductal breast carcinoma (IDC). Post-ablation magnetic resonance imaging (MRI) was compared with surgical pathology in evaluation of residual post-ablation IDC and ductal carcinoma in situ. METHODS: Patients with a single focus of IDC 20 mm or smaller by pre-ablation MRI were treated with PLA. The patients underwent a 28-day post-ablation MRI, followed by surgical resection. Cell viability criteria were applied to pre- and post-ablation pathology specimens, which evaluated hematoxylin-eosin (H&E), cytokeratin (CK) 8/18, estrogen receptor, and Ki67 staining patterns. RESULTS: In this study, 61 patients were reported as the intention-to-treat cohort for determination of PLA efficacy. Of these 61 patients, 51 (84%) had complete tumor ablation confirmed by pathology analysis. One subject's MRI imaging was not performed per protocol, which left 60 subjects evaluable for MRI pathology correlation. Five patients (8.3%) had residual IDC shown by both MRI and pathology. Post-ablation discordance was noted between MRI and pathology, with four patients (6.7%) false-positive and four patients (6.7%) false-negative. The negative predictive value (NPV) of MRI for all the patients was 92.2% (95% confidence interval [CI], 71.9-91.9%). Of the 47 patients (97.9%) with tumors 15 mm or smaller, 46 were completely ablated, with an MRI NPV of 97.7% (95% CI, 86.2-99.9%). CONCLUSIONS: Percutaneous laser ablation is a potential alternative to surgery for treatment of early-stage IDC. Strong correlations exist between post-ablation MRI and pathologic alterations in CK8/18, ER, and Ki67 staining.

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 the effectiveness of the prepectoral breast reconstruction with Braxon dermal matrix: First multicenter European report on 100 cases.

We report the outcomes of the European prospective study on prepectoral breast reconstruction using preshaped acellular dermal matrix for complete breast implant coverage. Seventy-nine patients were enrolled between April 2014 and August 2015 all over Europe using a single protocol for patient selection and surgical procedure, according to the Association of Breast Surgery and British Association of Plastic Reconstructive and Aesthetic Surgeons joint guidelines for the use of acellular dermal matrix in breast surgery. The preshaped matrix completely wraps the breast implant, which is placed above the pectoralis major, without detaching the muscle. A total of 100 prepectoral breast reconstructions with complete implant coverage were performed. This series, with mean follow-up of 17.9 months, had two cases of implant loss (2.0%) including one necrosis of the nipple and one wound breakdown (1.0% respectively). No implant rotations were observed. Good cosmetic outcomes were obtained with natural movement of the breasts and softness to the touch; none of the patients reported experiencing pain or reduction in the movements of the pectoralis major muscle postoperatively. The use of preshaped acellular dermal matrix for a complete breast implant coverage in selected patients is safe and gives satisfactory results, both from the aesthetic view point and the low postoperative complication rates. Further studies reporting long-term outcomes are planned.

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.

Exploring information provision in reconstructive breast surgery: A qualitative study.

OBJECTIVE: Women considering reconstructive breast surgery (RBS) require adequate information to make informed treatment decisions. This study explored patients' and health professionals' (HPs) perceptions of the adequacy of information provided for decision-making in RBS. METHODS: Semi-structured interviews with a purposive sample of patients who had undergone RBS and HPs providing specialist care explored participants' experiences of information provision prior to RBS. RESULTS: Professionals reported providing standardised verbal, written and photographic information about the process and outcomes of surgery. Women, by contrast, reported varying levels of information provision. Some felt fully-informed but others perceived they had received insufficient information about available treatment options or possible outcomes of surgery to make an informed decision. CONCLUSIONS: Women need adequate information to make informed decisions about RBS and current practice may not meet women's needs. Minimum agreed standards of information provision, especially about alternative types of reconstruction, are recommended to improve decision-making in RBS.

Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.

BACKGROUND: Four previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation. METHODS: In the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35-70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928. FINDINGS: Between April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16.0 years (IQR 14.1-17.6), 601 breast cancers have been reported (251 [7.0%] in 3579 patients in the tamoxifen group vs 350 [9.8%] in 3575 women in the placebo group; hazard ratio [HR] 0.71 [95% CI 0.60-0.83], p<0.0001). The risk of developing breast cancer was similar between years 0-10 (226 [6.3%] in 3575 women in the placebo group vs 163 [4.6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0.72 [95% CI 0.59-0.88], p=0.001) and after 10 years (124 [3.8%] in 3295 women vs 88 [2.6%] in 3343, respectively; HR 0.69 [0.53-0.91], p=0.009). The greatest reduction in risk was seen in invasive oestrogen receptor-positive breast cancer (HR 0.66 [95% CI 0.54-0.81], p<0.0001) and ductal carcinoma in situ (0.65 [0.43-1.00], p=0.05), but no effect was noted for invasive oestrogen receptor-negative breast cancer (HR 1.05 [95% CI 0.71-1.57], p=0.8). INTERPRETATION: These results show that tamoxifen offers a very long period of protection after treatment cessation, and thus substantially improves the benefit-to-harm ratio of the drug for breast cancer prevention. FUNDING: Cancer Research UK (UK) and the National Health and Medical Research Council (Australia).

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.

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial.

BACKGROUND: Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319. FINDINGS: 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, p<0·0001). The predicted cumulative incidence of all breast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836). INTERPRETATION: Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer. FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.

Multiple Step-section Frozen Section sentinel lymph node biopsy--a review of 717 patients.

Sentinel Lymph Node Biopsy (SLNB) is the standard of care for axillary staging in breast cancer. Multiple Step-section Frozen Section (MSFS) analysis is used in our institution for SLNB. This is performed intra-operatively by freezing sentinel lymph nodes to obtain multiple step-sections which are examined histologically for evidence of metastases. Patients whose sentinel lymph nodes contained macrometastases proceeded to an axillary node clearance during the same operation. 717 patients over a two and a half year period had MSFS analysis. With regards to macrometastases, MSFS analysis had a sensitivity of 93.8%, a specificity of 99.3%, a positive-predictive value of 97.4% and a negative-predictive value of 98.2%. MSFS analysis of sentinel lymph nodes is a safe and accurate procedure. It is a relatively cost-effective alternative to molecular technologies relying on DNA amplification and more accurate than standard frozen section or touch-prep cytology.

Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study.

BACKGROUND: Mammographic breast density is a strong risk factor for breast cancer. Tamoxifen, which reduces the risk of breast cancer in women at high risk, also reduces mammographic breast density. However, it is not known if tamoxifen-induced reductions in breast density can be used to identify women who will benefit the most from prophylactic treatment with this drug. METHODS: We conducted a nested case-control study within the first International Breast Cancer Intervention Study, a randomized prevention trial of tamoxifen vs placebo. Mammographic breast density was assessed visually and expressed as a percentage of the total breast area in 5% increments. Case subjects were 123 women diagnosed with breast cancer at or after their first follow-up mammogram, which took place 12-18 months after trial entry, and control subjects were 942 women without breast cancer. Multivariable logistic regression was used to adjust for other risk factors. All statistical tests were two-sided. RESULTS: In the tamoxifen arm, 46% of women had a 10% or greater reduction in breast density at their 12- to 18-month mammogram. Compared with all women in the placebo group, women in the tamoxifen group who experienced a 10% or greater reduction in breast density had 63% reduction in breast cancer risk (odds ratio = 0.37, 95% confidence interval = 0.20 to 0.69, P = .002), whereas those who took tamoxifen but experienced less than a 10% reduction in breast density had no risk reduction (odds ratio = 1.13, 95% confidence interval = 0.72 to 1.77, P = .60). In the placebo arm, there was no statistically significant difference in breast cancer risk between subjects who experienced less than a 10% reduction in mammographic density and subjects who experienced a greater reduction. CONCLUSION: The 12- to 18-month change in mammographic breast density is an excellent predictor of response to tamoxifen in the preventive setting.

Use of briefings and debriefings as a tool in improving team work, efficiency, and communication in the operating theatre.

INTRODUCTION: Team work, communication, and efficiency in the operating theatre are widely recognised to be suboptimal. Poor communication is the single biggest cause of medical error. The surgical operating theatre is a potentially highly stressed environment where poor communication can lead to fatal errors. The objectives of this study were to assess the effects briefings and debriefings had on theatre start time, list lengths, and the staff's impression of these meetings. MATERIALS AND METHODS: Briefings and debriefings were conducted before the start of theatre lists over a 6 month period in 2007 in a district general hospital in north Bristol, UK. Both quantitative and qualitative data were collected. Using the hospital theatre database, theatre start and finish time was found and list length calculated. A questionnaire was devised and used to assess staff attitude to the briefings and debriefings. RESULTS: Staff felt that the briefings highlighted potential problems, improved the team culture, and led to organisational change. Theatre start times tended to be earlier and lists lengths were shorter when briefings were conducted, although this only reached statistical significance on one type of list. DISCUSSION: Briefings and debriefings had a positive impact on teamwork and communication. The lists ran more efficiently and briefings did not delay the theatre start times-in fact, the lists tended to start earlier.

Assessment of cosmesis after breast reconstruction surgery: a systematic review.

BACKGROUND: Breast reconstruction (BR) is undertaken to improve cosmetic outcomes, but how this is optimally assessed is uncertain. This review summarises current methods for assessing cosmesis after reconstructive surgery and makes recommendations for future practice. METHODS: A comprehensive systematic review identified all studies with 20 or more participants that evaluated the cosmetic outcome of BR. Four evaluation criteria (reporting of study inclusion criteria, type and timing of BR and timing of assessment) were used to assess study quality. Articles reporting at least three of the four criteria were considered robust and further summarised to report methods of cosmetic assessment, assessor details and the scoring systems used. RESULTS: 122 primary papers assessed cosmesis in 11,308 women with median follow-up of 28.8 months (range 18.0-42.9 months). Cosmesis was assessed by either healthcare professionals or patients in 33 (27.1%) and 37 studies (30.3%), respectively, and by both professionals and patients in 52 (42.6%). Professional assessments included 43 (40.2%) clinical, 49 (45.8%) photographic and 13 (12.1%) geometric assessments conducted by between 1 and 26 observers. Surgeons were most frequently involved in assessments (n = 71, 67.6%), but in 38 (36.1%) papers the assessor's profession was not reported. Twenty-seven (25.7%) papers used previously published assessment scale. Patients' views were assessed in 89 studies, using questionnaires (n = 63) or interviews (n = 12); 14 (15.7%) did not report how patients' views were obtained. CONCLUSIONS: Current methods for assessing the cosmetic outcome of BR vary widely. A valid patient-centred assessment method is required to fully understand the outcomes of BR and to inform decision-making.

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.

A prospective longitudinal study of cosmetic outcome in immediate latissimus dorsi breast reconstruction and the influence of radiotherapy.

BACKGROUND: Immediate breast reconstruction may result in superior cosmetic outcomes as a result of the preservation of the skin envelope. The impact of implant use and radiotherapy (RT) on the cosmetic outcome of latissimus dorsi (LD) breast reconstruction, however, has never been prospectively evaluated with adequate long-term follow-up. METHODS: Women undergoing immediate LD breast reconstruction from January 2000 to February 2007 underwent photographic assessment and clinical evaluation for breast retraction analysis (BRA) at 3, 6 and 12 months postoperatively and on the anniversary of their surgery. The resulting photographs were subject to panel cosmetic assessment. A patient-reported cosmetic outcome questionnaire and the body image scale (BIS) were administered to each woman at a single time point to coincide with the anniversary of their surgery. Multilevel linear regression modelling was used to analyse the results. RESULTS: Seventy-three women underwent 53 implant-assisted LD breast reconstructions and 20 autologous procedures with a mean follow-up of 2.71 years. The incidence of radiotherapy in this cohort was 43%. RT over time adversely influenced overall cosmetic outcome as assessed by the panel (P = 0.0002), and BRA (P = 0.033), both of which were significantly worse in the implant-assisted group (P = 0.020). Patient reporting of overall cosmetic outcome and BIS, however, did not differ significantly between the LD groups or following RT. CONCLUSION: Radiotherapy may adversely affect the cosmetic outcome of latissimus dorsi breast reconstruction, particularly if an implant is used, but this is not universal. Patient assessment of their cosmetic outcome may, however, differ significantly from the clinician's view.