C.R. Wilson

Attitudes and training of research fellows in surgery: national questionnaire survey

Traditionally, clinical research fellowships are occupied by junior trainees and are used as a stepping stone not only to an academic career but more commonly to the higher specialist training scheme. In the United Kingdom, clinical academic medicine is having difficulties in recruitment, especially to senior posts, and in academic surgery several professorial chairs remain vacant because of a shortage of suitable candidates.1 Analysis of research papers presented at surgical meetings over the past 20 years has shown a considerable reduction in the number of randomised clinical trials and a corresponding increase in the number of basic scientific projects.2 Surgical research has recently been criticised for its poor quality and lack of evidence based “patient oriented research that matters.”3 Training in research methods is important for surgeons conducting research, and a previous survey showed that this view is shared by consultant …

The need for DXA assessment of breast cancer patients following 5 years tamoxifen prior to starting an aromatase inhibitor.

Abstract #6141 Introduction: Aromatase inhibitors are increasingly being used in the adjuvant treatment of post-menopausal women with breast cancer. They are more effective than tamoxifen in terms of disease free survival and have a different side effect profile, all causing loss of bone mineral density. They can be introduced at different points in the adjuvant pathway. It has been postulated that if given in the extended setting, letrozole after 5 yrs tamoxifen, bone health may be less important. Tamoxifen is reported to increase bone mineral density so should make subsequent bone mineral density reduction with letrozole less significant. The aim of this study was to determine whether DXA scanning should be undertaken in women following 5 yrs of tamoxifen prior to starting letrozole.
 Method: 166 women who had completed 5 years of tamoxifen underwent DXA with assessment of vertebral morphometry and risk factors associated with osteoporosis and fracture rate.
 Results: Mean age was 63yrs (standard deviation [S.D] 10yrs); 154 women were post menopausal being at least 2 years after their last menstrual period; 12 women were unable to recall when they menopaused. Mean t-score and S.D was calculated at each site; spine -1.26(1.3); femoral neck -1.16(1.1) and total hip -0.91(1.1). Results were categorised by lowest t-score.
 Conclusion: We have demonstrated that of 166 women following completion of 5 yrs tamoxifen 26.5% have osteoporosis and 35.5% osteopenia. 28% required treatment with bisphosphonates. It cannot be assumed that Tamoxifen will cause a sufficient increase in BMD to render DXA scanning unnecessary. All patients should have DXA scanning following completion of 5 yrs tamoxifen prior to commencing letrozole. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6141.

P3-07-30: Applying the Findings of the Z11 Trial to a UK Practice.

Introduction: The finding of a positive sentinel node is currently managed by further Level III axillary lymph node clearance (ALNC). The rationale behind this approach is that of local disease control, but there is little evidence that axillary lymph node clearance results in a reduction in axillary recurrence or in mortality. ALNC is however associated with increased morbidity (lymphoedema, nerve damage, reduced shoulder function) and significantly prolongs hospital stay. The Z11 trial suggests that ALNC following positive sentinel node biopsy does not result in lower axillary recurrence rates compared to the group in whom clearance was not undertaken and has obvious implications for evidence-based practice. The Z11 trial has strict inclusion criteria (T1/T2 tumour, breast conservation surgery) with all patients receiving adjuvant whole breast radiotherapy and systemic chemotherapy or endocrine therapy. For patients who do not meet the patient population of Z11, such as women undergoing mastectomy, the Sloane-Kettering predictive normogram provides an estimate of risk for residual axillary disease after positive sentinel node biopsy and the estimate of this risk may inform the clinical decision to clear the axilla based on individual cancer characteristics. Methods: Our population comprises both symptomatic and screening patients, with an axillary positivity rate of approximately a third. This study was undertaken to assess the impact that Z11 would have on our practice. Our prospectively maintained records were searched for ALNC patients treated between 2003 and 2011. We assessed the number of node-positive patients conforming to Z11 criteria and the number who demonstrated residual axillary positivity at clearance after a positive sentinel node. The axillary recurrence rate for this group after ALNC was recorded. We calculated the number of clearances that could have been avoided, and extrapolated the reduction in morbidity in lymphodema and nerve damage using the audited incidence of these complications in our institution. We calculated the financial cost saving in terms of theatre usage and hospital stay. In addition, we assessed whether the Memorial Sloane Kettering predictive normogram is useful in the prediction of residual axillary disease for the group of patients excluded from the Z11 cohort. Results: 1601 patients underwent axillary staging. 65% of our patients with node-positive disease were identified pre-operatively with ultrasound and biopsy and proceeded directly to ALNC. Our overall axillary recurrence rate was low ( Discussion: Using these criteria nearly 25% of axillary clearances in our population of breast cancer patients could be avoided with obvious cost savings both in terms of morbidity and finance, considerations that are important in planning our service for the future. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-30.

A Multi-Center Study To Determine the Optimum Duration of Neoadjuvant Letrozole on Tumour Regression To Permit Breast Conserving Surgery – An Interim Analysis.

Background: Neoadjuvant letrozole is an attractive alternative to chemotherapy for post menopausal women with large, ER positive breast cancer, who are destined for mastectomy but would prefer breast conservation. Prospective studies have not investigated treatment duration beyond 6 months and retrospective studies suggest useful responses can occur after this period.Materials and Methods: This trial is a prospective, UK centrally quality assured, multi-centre, longitudinal study to assess the optimal duration of neoadjuvant letrozole treatment to allow breast conserving surgery for a period of up to12 months. Post menopausal women with large (≥T2), ER and/or PgR positive primary tumours, not considered eligible for breast conservation, were commenced on neoadjuvant letrozole and response was assessed every 2 months with clinical and ultrasound examination until sufficient shrinkage for breast conservation, progression or 12 months had been reached. Ultrasound and Mammography were undertaken at baseline and end-point. We present the initial analysis for time to response and breast conservation.Results: By January 2009, 103 women were available for analysis. 23 (22.3%) had undergone a mastectomy, 60 (58.3%) had achieved breast conservation and 20 (19.4%) remained under evaluation within the trial. The mean age of the group was 74.1 years (52-92). 25 (24.3%) had invasive lobular cancer and 13 (12.6%) had grade 3 tumours. 22 (21.4%) were node positive.Figure 1. Kaplan-Meier plot for time (days) to response sufficient for breast conservation.25% had breast conservation by 5.8 months, 50% by 8.2 months and 75% by 12 months. Median time to breast conservation was 8.2 months (95% CI 6.4-9.3)Figure 2. Median change in tumour volume from baselineAfter an initial rapid response in the first 4 months, the rate of response was slower and constant for a further 6 months. Tumour volume reduction to permit breast conservation varied between 65 and 80% .Discussion: This interim analysis indicates that the conventional treatment period of 4 to 6 months of neoadjuvant letrozole should be revised. For most women longer duration will increase the likelihood of achieving sufficient volume reduction to allow breast conserving surgery. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1082.

The effect of quantitative oestrogen receptor expression on recurrence in postmenopausal women with early stage breast cancer.

Abstract #1131 Introduction: Approximately 15% of postmenopausal women treated with adjuvant tamoxifen will experience disease recurrence within 5 years. This may reflect resistance of the primary tumour to tamoxifen. We aim to determine if quantitative oestrogen receptor (ER) expression has an effect on the incidence and type of recurrence in this patient group.
 Methods: All postmenopausal women diagnosed with early stage breast cancer between 1995 and 2001 in 3 hospitals were included. All ER immunohistochemistry was performed on one site by a single pathologist. A percentage of ER expression was assigned to each tumour. Patients were grouped into high ER (≥70% expression) and low ER ( Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1131.

Abstract P2-13-14: Does therapeutic mammoplasty reduce mastectomy rates?

Introduction: Therapeutic mammoplasty (TM) is increasing in popularity as a method for enhancing breast conserving surgery. Studies have shown it’s oncologically safe, whilst improving cosmetic outcome1,2,3. Therapeutic mammoplasty has been gaining popularity in West of Scotland over the past five years. Initially it was thought this may reduce requirement for mastectomy and immediate reconstruction. We have recorded type of surgery patients would have required had they not been suitable for TM, looking at changing demographic of surgical workload. Methods: Prospective data collected about patients undergoing TM in West of Scotland since 2011 in Victoria Infirmary, Western Infirmary and in NHS Lanarkshire. We reviewed clinical indications for TM, surgical alternative, Body Mass Index (BMI) and smoker status. Results: Seventy-nine patients were identified. In 67 cases, alternative surgical option of mastectomy or standard conservation was recorded. Mean BMI was 29. 41% of patients had contralateral surgery for symmetry at the same time. In 28 cases (35%) TM avoided need for mastectomy. In 39 cases (49%) it was felt that cosmetic result would be improved by TM compared with standard conservation. During the study period, rates of mastectomy with immediate reconstruction as a proportion of total number of treated cancers have remained similar. Conclusions: Whilst introduction of therapeutic mammoplasty in our region has improved options offered to patients and likely cosmetic outcomes, it has not had a major impact in reducing mastectomy rates or demand for immediate reconstruction. It has probably increased surgical workload of plastic surgeons as these cases are often performed as joint procedures. References: 1. Iwuchukwu OC, Harvey JR, Dordea M, Critchley AC, Drew PJ. The role of oncoplastic therapeutic mammoplasty in breast cancer surgery – A review. Surgical Oncology. 2012;21:133-141 2. McCulley SJ, Macmillan RD. Planning and use of therapeutic mammoplasty – Nottingham approach. British Journal of Plastic Surgery. 2005;58:889-901 3. Clough K, Lewis J, Couturand B, Fitoussi A, Nos C, Falcou M. Oncoplastic techniques allow extensive resections for breast-conserving therapy of breast carcinomas. Annals of Surgery. 2003;237(1):26-34. Citation Format: Jennifer Pollard, Pang Wong, James Mansell, Juliette Murray, Alison Lannigan, Julie Doughty, Laszlo Romics, Sheila Stallard, Christopher Wilson. Does therapeutic mammoplasty reduce mastectomy rates? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-14.

0188 Distant recurrence and subsequent mortality in breast cancer patients treated at 5 UK centres

F. Zagouri1, A. Bamias2, P. Papakostas3, A. Karadimou1, E. Bournakis1, M. Dimopoulos1, G. Fountzilas4, C.A. Papadimitriou5. 1Department of Clinical Therapeutics, 21Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, 3Department of Medical Oncology, Hippocrateio Hospital, Athens, 4Department of Medical Oncology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Thessaloniki, 5Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Athens, Greece

The Influence of Mode of Presentation on the Pattern of Recurrence in Early Breast Cancer (EBC).

IntroductionAn early peak in recurrence exists in women with EBC. This may be explained underlying tumour biology or a reaction to surgery. Screen detection has been shown to have a prognostic effect independent of disease stage suggesting a connection with underlying tumour biology. We aim to determine if the pattern of recurrence differs between modes of presentation.MethodsData from 3 centres in Glasgow of consecutive women aged between 50-65yrs with early stage breast cancer (EBC) diagnosed between 1995 and 2001 were examined. Recurrence was defined as invasive disease at any site. Patients were grouped by mode of presentation into screen detection and symptomatic. Kaplan Meier and time dependent Cox analysis were performed.Results1534 women were included with a median follow up of 5.5yrs. Mode of presentation was screening in 1007 (65.6%) women. At 2.5yrs cumulative recurrence was 2.5% (95% CI 1.5-3.5) in the screen detected group and 9.7% (7.2-12.2) in the symptomatic group. At five years the corresponding rates were 7.8% (6.0-9.6) vs. 19.1% (15.6-22.6). Time dependent multivariate analysis showed that the difference in the risk of recurrence between the modes of presentation was significantly different within 2.5yrs from diagnosis compared with later than 2.5yrs (p = 0.019). The hazard ratio for recurrence within 2.5 yrs was 0.59 (95% CI 0.34-1.00, p=0.05) and after 2.5yrs was 1.23 (0.84-1.80, p =0.285).ConclusionsThese results suggest that women with screen detected cancers have a better prognosis initially following diagnosis independent of disease stage. However this additional benefit isn9t maintained with longer follow up. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3056.

Does the Additional Prognostic Benefit of Screen Detection in Early Breast Cancer Apply to All Patients

Introduction Screen detection may confer prognostic benefit independent of disease stage in EBC leading to suggestions that mode of presentation should be considered when deciding adjuvant therapy. We aim to determine if this additional prognostic benefit is seen in all patients. Methods Data from 3 centres in Glasgow of consecutive women aged between 50-65yrs with EBC diagnosed between 1995 and 2001 were examined. Patients were grouped by mode of presentation into screen detection and symptomatic. Breast cancer specific survival was the endpoint. Multivariate analysis including interaction between mode of presentation and pathology was performed with further subgroup analysis if the interaction was significant. Results 1534 women were included with a median follow up of 5.5yrs. Mode of presentation was screening in 1007 (65.6%) women. After adjustment for pathology screen detection had no significant survival benefit: HR 0.73 (0.50-1.08, p = 0.116). Mode of presentation had an independently significant interaction with both nodal status and ER status (p = 0.003 and p = 0.01 respectively). Further analysis demonstrated that screening was an independent predictor of survival in the 1-3 node positive group (HR 0.33 (0.15-0.73), p = 0.006); the ER positive group (HR 0.53 (0.31-0.89), p = 0.017) and in the moderate NPI group only (HR 0.54 (0.31-0.94), p = 0.030). Conclusions These results provide evidence of a significant interaction between mode of presentation and pathology. Further research is needed before incorporating mode of presentation into decisions regarding adjuvant therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4007.

Socio-economic deprivation independently predicts early recurrence in estrogen receptor positive breast cancer.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #6081 Introduction: Socio-economic deprivation is associated with reduced survival in breast cancer, but little is known about how it affects the pattern of disease recurrence. We investigated the relationships between deprivation, other risk factors and recurrence in post-menopausal women with operable ER+ breast cancer. Methods: Patients who underwent potentially curative surgery for ER+ breast cancer between 1995 and 2005 at four UK centres were studied. Those patients whose area of residence was ranked in the highest quintile group according to the appropriate national Index of Multiple Deprivation were classed as deprived. The cumulative risk of recurrence was calculated using the Kaplan-Meier method, and hazard ratios were calculated using conventional and time-dependent Cox regression analysis stratified by centre. Results: 4110 patients were available for analysis, of whom 821 (20.0%) were classed as deprived. The median age at diagnosis was 62 years in both deprived and non-deprived groups. Tumour size and grade did not vary with deprivation status, but nodal involvement (38.0% vs 34.3%, p=0.05, Fishers exact test) and lymphovascular invasion (28.1% vs 23.6%, p=0.01) were more prevalent in deprived patients. The latter were also more likely to undergo mastectomy (53.3% vs 47.2%, p=0.002) and less likely to receive adjuvant radiotherapy (50.4% vs 58.5%, P<0.001) or chemotherapy (19.1% vs 22.8%, p=0.03). Median follow up was 5 years from diagnosis. Raw cumulative recurrence at 2.5 years was 8.4% (95% confidence interval 6.4-10.4) in deprived and 6.1% (5.3-6.9) in non-deprived patients. At 5 years the corresponding rates were 15.8% (13.1-18.5) and 13.3% (11.9-14.7). Only distant recurrence contributed to this difference, the local and contralateral recurrence rates being almost identical in deprived and non-deprived groups. Time-dependent Cox regression analysis showed that deprivation was a significantly stronger predictor of recurrence within 2.5 years of diagnosis than at later intervals, with or without adjustment for other prognostic variables (p<0.05). For recurrence within 2.5 years, the unadjusted hazard ratio for deprivation was 1.64 (95% CI 1.22-2.22, p=0.001). After adjustment for age, mode of presentation, pathological variables and treatment, the hazard ratio was 1.51 (1.07-2.14, p=0.02). Conclusions: Post-menopausal women with ER+ breast cancer who are resident in areas of high deprivation are at increased risk of early recurrence, independently of known differences in tumour pathology and treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6081.