Survivin expression in in situ and invasive breast cancer relates to COX-2 expression and DCIS recurrence

In lung cancer cyclooxygenase-2 (COX-2) expression has been reported to stabilise survivin, an inhibitor of apoptosis (IAP) which prevents cell death by blocking activated caspases. COX-2 expression limits the ubiquitination of survivin, protecting it from degradation. To determine if COX-2 expression in breast cancer showed an association with survivin expression, we assessed the levels of each protein in ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC); relating expression patterns to recurrence of DCIS after surgery. Patterns of COX-2 and survivin expression were determined by intensity-graded immunohistochemistry of the primary tumours. Patients with DCIS (n=161) which had either recurred (n=47) or shown no evidence of recurrence (n=114) 5 years following primary surgery were studied. These were compared to 58 cases of IBC. Survivin was expressed in the cytoplasm of 59% of DCIS and 17% of IBC. High levels of both cytoplasmic survivin and COX-2 expression significantly correlated to DCIS recurrence. COX-2 expression was present in 72% of DCIS, and levels of expression positively correlated with cytoplasmic survivin expression in DCIS and invasive disease. The majority of DCIS that recurred expressed both proteins (69%) vs 39% nonrecurrent. Recurrence was not seen in DCIS lacking both proteins at 5 years (P=0.001). Expression of the IAP survivin is increased in DCIS and correlates closely with COX-2 expression. Increased expression of IAP, (leading to reduced apoptosis) may explain the effect of COX-2 in increasing recurrence of DCIS after surgical treatment

Short-term safety outcomes of mastectomy and immediate implant-based breast reconstruction with and without mesh (iBRA): a multicentre, prospective cohort study

Background Use of biological or synthetic mesh might improve outcomes of immediate implant-based breast reconstruction—breast reconstruction with implants or expanders at the time of mastectomy—but there is a lack of high-quality evidence to support the safety or effectiveness of the technique. We aimed to establish the short-term safety of immediate implant-based breast reconstruction performed with and without mesh, to inform the feasibility of undertaking a future randomised clinical trial comparing different breast reconstruction techniques. Methods In this prospective, multicentre cohort study, we consecutively recruited women aged 16 years or older who had any type of immediate implant-based breast reconstruction for malignancy or risk reduction, with any technique, at 81 participating breast and plastic surgical units in the UK. Data about patient demographics and operative, oncological, and complication details were collected before and after surgery. Outcomes of interest were implant loss (defined as unplanned removal of the expander or implant), infection requiring treatment with antibiotics or surgery, unplanned return to theatre, and unplanned re-admission to hospital for complications of reconstructive surgery, up to 3 months after reconstruction and assessed by clinical review or patient self-report. Follow-up is complete. The study is registered with the ISRCTN Registry, number ISRCTN37664281. Findings Between Feb 1, 2014, and June 30, 2016, 2108 patients had 2655 mastectomies with immediate implant-based breast reconstruction at 81 units across the UK. 1650 (78%) patients had planned single-stage reconstructions (including 12 patients who had a different technique per breast). 1376 (65%) patients had reconstruction with biological (1133 [54%]) or synthetic (243 [12%]) mesh, 181 (9%) had non-mesh submuscular or subfascial implants, 440 (21%) had dermal sling implants, 42 (2%) had pre-pectoral implants, and 79 (4%) had other or a combination of implants. 3-month outcome data were available for 2081 (99%) patients. Of these patients, 182 (9%, 95% CI 8–10) experienced implant loss, 372 (18%, 16–20) required re-admission to hospital, and 370 (18%, 16–20) required return to theatre for complications within 3 months of their initial surgery. 522 (25%, 95% CI 23–27) patients required treatment for an infection. The rates of all of these complications are higher than those in the National Quality Standards (<5% for re-operation, re-admission, and implant loss, and <10% for infection). Interpretation Complications after immediate implant-based breast reconstruction are higher than recommended by national standards. A randomised clinical trial is needed to establish the optimal approach to immediate implant-based breast reconstruction

Overdiagnosis and overtreatment of breast cancer: Progression of ductal carcinoma in situ: the pathological perspective

Ductal carcinoma in situ (DCIS) is encountered much more frequently in the screening population compared to the symptomatic setting. The behaviour of DCIS is highly variable and this presents difficulties in choosing appropriate treatment strategies for individual cases. This review discusses the current data on the frequency and rate of progression of DCIS, the value and limitations of clinicopathological and biological variables in predicting disease behaviour and suggests strategies to develop more robust means of predicting progression of DCIS

Abstract PD04-06: Molecular Phenotypes of DCIS predict Invasive and DCIS recurrence

Abstract Introduction: Molecular phenotypes of invasive breast cancer predict early recurrence and survival. DCIS exhibits similar phenotypes but their frequency and clinical significance remain uncertain. To determine whether molecular phenotypes of DCIS predict recurrence, 273 women (median age 57 years) with primary DCIS who were screened for or entered DCIS trials (Iressa/Lapatinib/ERISAC) in one unit from 1990–2010 were studied. Methods: HER2, oestrogen receptor (ER) and progesterone receptor (PR) expression within primary DCIS were established using immunohistochemistry within the trial protocols. HER2 was scored 0 (absent) to 3 (maximum). Scores ≥2 were taken as positive if amplified on FISH testing. ER and PR scored positive if ≥5% of cells stained. 64.2% patients were ER positive, 43.3% were HER2 positive and 31.8% were high-grade lesions. 94 underwent mastectomy whilst 185 had BCS. Results: There was an overall recurrence rate of 20.14% after a median follow-up period of 74 months (range 12–240). Of these recurrences, 36.4% were invasive. Conservation surgery (BCS) was used in 185 women who suffered 47 recurrences. Molecular phenotype predicted local recurrence by Log Rank analysis (P &amp;lt; 0.01) and invasive recurrences (P &amp;lt; 0.016) overall and in the BCS group remained predictive of invasive recurrence (p &amp;lt;0.005) and overall recurrence (p &amp;lt; 0.001). ER negative DCIS had higher invasive recurrence (p &amp;lt; 0.01: Chi-squared). Grade 3 was a weak predictor of overall (p &amp;lt; 0.02) but not invasive recurrence. HER2 positive DCIS had poorer cumulative 5-year disease-free survival than HER2 negative cases (p = &amp;lt;0.001, Kaplan-Meier), irrespective of ER status. On multivariate COX regression analysis, HER2 positivity was an independent predictor of increased recurrence risk (p = 0.01) H.R. 7.39, 95% CI 1.61–33.8) Discussion: Determination of molecular phenotypes of DCIS aids identification of women at high-risk of recurrence. ER-HER2+ patients need maximal adjuvant treatment to avoid invasive recurrence whereas lower-risk ER+HER2− patients might avoid adjuvant radiotherapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD04-06.</jats:p

Variation in the provision and practice of implant-based breast reconstruction in the UK: Results from the iBRA national practice questionnaire

Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50e80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0e3.0) and 2.0 plastic surgeons (IQR:1.0e3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n ¼ 62) and synthetic (n ¼ 25) meshes and in patient selection for these procedures.</p