Oncoplastic breast conservation surgery is oncologically safe when compared to wide local excision and mastectomy.

BACKGROUND: Support for the oncological safety of oncoplastic breast conservation surgery (OBCS) is mostly based on evidence comparing recurrence rates after OBCS to wide local excision (WLE). However, OBCS is often indicated for larger cancers and oncological results should also be compared to patients treated with mastectomy. In this study we compared recurrence and survival following OBCS, mastectomy and WLE. METHODS: Patients treated with OBCS between 2009 and 2012 were identified from a prospectively maintained database. For comparison, consecutive patients treated with WLE or mastectomy with or without immediate reconstruction (Ms ± IR) over the same time period were identified. Histological variables of patients were compared using Fisher Exact or Chi squared tests, and recurrence and survival were compared using Kaplan-Meier and Cox regression survival analysis. RESULTS: 980 patients' data were analysed (OBCS: n = 104; WLE: n = 558; Ms ± IR: n = 318). Tumour size, grade, nodal status, ER, and PR expression of patients treated with OBCS were all significantly more adverse compared with patients treated with WLE (p < 0.001). These histological variables were similar in patients treated with Ms ± IR and OBCS. 5-year local recurrence rates were similar in all three groups (WLE: 3.4 per cent, OBCS: 2 per cent, Ms ± IR: 2.6 per cent; log rank = 0.973), while distant recurrence rates were higher after Ms ± IR and OBCS (Ms ± IR:13.1 per cent, OBCS:7.5 per cent, WLE:3.3 per cent; log rank: p < 0.001). CONCLUSION: OBCS is oncologically safe in patients even when histological results are similar to patients treated with Ms ± IR.

How to compare the oncological safety of oncoplastic breast conservation surgery - To wide local excision or mastectomy?

BACKGROUND: Comparative studies suggest that patients treated with oncoplastic breast conservation surgery (OBCS) have similar pathology to patients treated with wide local excision (WLE). However, patients treated with OBCS have never been compared to patients treated with mastectomy. The aim of this study was to identify which control group was comparable to patients undergoing OBCS. METHODS: Commonly reported histopathological variables of patients treated with OBCS, WLE or mastectomy ± immediate reconstruction (Ms ± IR) were compared using Fisher Exact or Chi squared tests. RESULTS: 1000 patients' data were analysed (OBCS: n = 119; WLE: n = 600; Ms ± IR: n = 281). Tumour size was significantly bigger after OBCS than WLE (p < 0.001), but similar to Ms ± IR (p = 0.138). Tumour grade was higher after OBCS than WLE (p < 0.001), but similar to Ms ± IR (p = 0.497). More axillary nodes were involved in patients with OBCS than WLE (p < 0.001), but comparable to Ms ± IR (p = 0.175). ER and PR expressions were lower after OBCS compared to WLE (p = 0.007, p = 0.009), but identical to Ms ± IR (p = 1, p = 0.904 respectively). Differences in application of systemic (neo)adjuvant therapy followed the above trend. CONCLUSION: Striking similarities found between OBCS and mastectomy patients' histopathological results are in sharp contrast with previously published data. This study suggests that oncological outcomes following OBCS should be compared to mastectomy besides WLE.

Quality of information reporting in studies of standard and oncoplastic breast-conserving surgery.

The aim of this systematic review was to establish the completeness of reporting of key patient, tumour, treatment, and outcomes information in the randomized-controlled trials (RCTs) of standard breast-conserving surgery (sBCS) considered to be the 'gold-standard', and to compare this with the reporting of the same key criteria for all published studies of oncoplastic breast-conserving surgery (oBCS). Pubmed (1966 to 1st April 2013), Ovid MEDLINE (1966 to 1st April 2013), EMBASE (1980 to 1st April 2013), and the Cochrane Database of Systematic Reviews (Issue 4, 2013) were searched separately for the following terms: (i) 'oncoplastic AND breast AND surgery'; and (ii) 'therapeutic AND mammaplasty'. Only English language and full text articles were reviewed. Following a pilot evaluation of all studies, key reporting criteria were identified. 16 RCTs of sBCS (n = 11,767 patients) were included, and 53 studies met the inclusion criteria for oncoplastic BCS (n = 3236 patients), none of which were RCTs. No study reported all of the criteria identified, with a mean of 64% of key criteria (range, 55-75%) reported in studies of sBCS, and 54% of criteria (range, 10-85%) reported in studies of oBCS. It is therefore evident that there is much room for improvement in the quality of reporting is BCS studies. Standards are proposed to give future studies of BCS a framework for reporting key information and outcomes.

Use of boost radiotherapy in oncoplastic breast-conserving surgery - a systematic review.

BACKGROUND: The use of local boost radiotherapy to the tumour bed has been demonstrated in randomised-controlled trials to reduce local recurrence rates following breast-conserving surgery (BCS) and is the standard of care. Oncoplastic BCS techniques with parenchymal rearrangement present new challenges to the localisation of the tumour bed and therefore delivery of local boost radiotherapy. The aim of this review was to evaluate the reporting of boost radiotherapy in the oncoplastic BCS literature. METHODS: Pubmed, Ovid MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched for studies reporting oncoplastic BCS using volume displacement techniques. RESULTS: 24 studies met the inclusion criteria (n = 1933 patients). Use of boost radiotherapy was reported in 11 studies, in 2 of which it was for the treatment of incomplete or close margins, and marking of the tumour bed was only reported in 8 studies. None of the studies reported the number of patients where the tumour bed could not be localised. CONCLUSIONS: The use of local boost radiotherapy and tumour bed marking was not reported in the majority of studies of oncoplastic BCS. Future studies need to provide detailed information regarding the use of boost radiotherapy and difficulties determining the target volume so that current radiotherapy approaches can be reviewed and improved for these advanced techniques.

Oncoplastic breast conservation does not lead to a delay in the commencement of adjuvant chemotherapy in breast cancer patients.

INTRODUCTION: There is hardly any evidence that oncoplastic breast conservation surgery (OBCS) does not lead to a delay in the commencement of adjuvant chemotherapy. Although this is an integral part of overall oncological safety, no controlled studies have been published so far. Therefore, our aim was to determine whether OBCS led to a delay when compared to simple wide local excision (WLE), mastectomy (Ms) or mastectomy with immediate reconstruction (MsIR). METHODS: Breast cancer patients who required adjuvant chemotherapy after OBCS, WLE, Ms and MsIR were identified from prospectively maintained institutional databases. Time between multidisciplinary team decision to offer chemotherapy and delivery of first cycle of chemotherapy was measured and compared among the four groups of patients. RESULTS: time to chemotherapy of breast cancer patients (n = 169) treated with OBCS (n = 31) were 29 [16-58] days, while it was 29.5 [15-105] days after WLE (n = 66), 29 [15-57] days after Ms (n = 56) and 31 [15-58] days after MsIR (n = 16). A combined analysis involving all four groups demonstrated no statistically significant difference (p = 0.524). Similarly, inter-group analysis revealed no significant differences in between patients treated with OBCS compared to any of the three control groups (OBCS to WLE: p = 0.433; OBCS to Ms: p = 0.800; OBCS to MsIR: p = 0.405). CONCLUSION: OBCS seems as safe as WLE, Ms or MsIR in terms of delivery of adjuvant chemotherapy, and, therefore, should not adversely affect breast cancer outcome in this respect.

Male mastectomy: an oncoplastic solution to improve aesthetic appearance.

Mastectomy for breast cancer in men typically results in an unsatisfactory aesthetic appearance due to loss of the normal male chest contour. In this article we present two case studies and a new oncoplastic surgical technique that has given excellent aesthetic results for this challenging problem.

The relationship between components of tumour inflammatory cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer.

BACKGROUND: The importance of the components of host local inflammatory response in determining outcome in primary operable ductal invasive breast cancer is not clear. The aim of this study was to examine the relationship between components of the tumour inflammatory cell infiltrate and standard clinicopathological factors including hormone status (oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)-2), Ki-67 and survival in patients with primary operable invasive ductal breast cancer. METHODS: Tumour inflammatory cell infiltrate, hormone status (ER, PR and HER-2), Ki-67 and standard clinicopathological factors were determined using routine pathological and immuno-histochemical techniques in 468 patients. RESULTS: The large majority (94%) of ductal tumours had evidence of inflammatory cell infiltrate. The general inflammatory cell infiltrate was positively associated with high grade (P<0.001), the absence of ER (P<0.001), the absence of PR (P<0.01), the presence of vascular invasion (P<0.05) and high lymphocytic infiltrate, plasma cell infiltrate, other inflammatory cell infiltrate and macrophage infiltrate (all P<0.001). The median follow-up of the survivors was 165 months. During this period, 93 patients died of their cancer. On univariate analysis, stratified for ER status, tumour size (P<0.01), lymph node involvement (P<0.001), tumour plasma cell infiltrate (P<0.001), other inflammatory cell infiltrate (P<0.05) and treatment (P<0.05) were associated with poorer cancer-specific survival whereas lymphocyte infiltrate (P<0.001) was associated with improved cancer-specific survival. On multivariate analysis, stratified for ER status, lymph node involvement (P<0.05) was independently associated with poorer cancer-specific survival whereas increased tumour lymphocyte infiltrate (P<0.001) was independently associated with improved cancer-specific survival. CONCLUSION: The results of this study show that, using routine histology, the general inflammatory cell infiltrate was a common feature and was positively associated with high grade, the absence of ER, the absence of PR, the presence of vascular invasion and high-grade infiltration of lymphocytes, plasma cells, other inflammatory cells and macrophages. Also, that within a mature cohort of patients, a high lymphocytic infiltrate was associated with improved survival, independent of clinicopathological characteristics including ER status, in primary operable ductal invasive breast cancer. These results rationalise previous work and provide a sound basis for future studies in this important area of breast cancer research.

Ten-year follow-up of skin-sparing mastectomy followed by immediate breast reconstruction.

BACKGROUND: The oncological safety of skin-sparing mastectomy (SSM) followed by immediate breast reconstruction (IBR) is debated owing to a presumed compromise in the completeness of mastectomy. Current evidence is poor as it is based mostly on short-term follow-up data from highly selected patients. METHODS: A prospectively maintained institutional database was searched to identify patients who underwent SSM and IBR between 1995 and 2000. A retrospective review of medical records was carried out, including only patients with ductal carcinoma in situ and invasive breast cancer. During this time all patients treated with mastectomy were offered IBR regardless of tumour stage. RESULTS: Follow-up data from 253 consecutive patients with IBR were reviewed. Patients with incomplete follow-up data and those undergoing SSM for recurrent disease following previous lumpectomy were disregarded, leaving 207 for analysis. Offering IBR to all women requiring mastectomy resulted in a large proportion of patients with advanced disease. During a median follow-up of 119 months, 17 (8·2 per cent) locoregional, six (2·9 per cent) local and 22 (10·6 per cent) distant recurrences were detected; the overall recurrence rate was 39 (18·8 per cent). Overall recurrence rate was associated with axillary lymph node metastasis (P = 0·009), higher stage (P < 0·001) and higher tumour grade (P = 0·031). The breast cancer-specific survival rate was 90·8 per cent (19 of 207 women died from recurrence). CONCLUSION: Based on these long-term follow-up data, SSM combined with IBR is an oncologically safe treatment option regardless of tumour stage.

Comparison of visual and automated assessment of Ki-67 proliferative activity and their impact on outcome in primary operable invasive ductal breast cancer.

BACKGROUND: Immunohistochemistry of Ki-67 protein is widely used to assess tumour proliferation, and is an established prognostic factor in breast cancer. There is interest in automating the assessment of Ki-67 labelling index (LI) with possible benefits in handling increased workload, with improved accuracy and precision. PATIENTS AND METHODS: Visual and automated assessment of Ki-67 LI and survival were examined in patients with primary operable invasive ductal breast cancer. Tissue microarrays (n=379 patients) immunostained for Ki-67 were scored visually and automatically with the Slidepath Tissue IA system. RESULTS: Visual and automated Ki-67 LI were in excellent agreement (ICCC=0.96, P<0.001). On univariate analysis, visual (P<0.001) and automated Ki67 LI (P<0.05) were associated with cancer-specific survival in patients with invasive ductal breast cancer overall and in patients who received endocrine therapy (Tamoxifen) (P<0.01 for visual and P<0.05 for automated scoring). CONCLUSION: Automated assessment of Ki-67 LI would appear to be comparable to visual Ki-67 LI. However, automated Ki-67 LI assessment was inferior in predicting cancer survival in patients with breast cancer, including patients who received Tamoxifen.

Impact of national guidelines on family history breast cancer surveillance.

The breast cancer risk of women already under family history surveillance was accurately assessed according to national guidelines in an attempt to rationalize the service. Women attending two breast units in Glasgow between November 2003 and February 2005 were included. One thousand and five women under annual surveillance were assessed and had their relatives diagnoses verified. Four hundred and ninety-seven women were at significantly increased risk and eligible for follow-up. Five hundred and eight (50%) women attending were not eligible for family history surveillance, and 498 (98%) of these women accepted discharge. In conclusion, national guidelines have helped to more clearly define women who should undergo surveillance. This avoids unnecessary and potentially harmful routine investigations, and the service has been improved.

Poor survival outcomes in HER2-positive breast cancer patients with low-grade, node-negative tumours.

We present a retrospective analysis on a cohort of low-grade, node-negative patients showing that human epidermal growth factor receptor 2 (HER2) status significantly affects the survival in this otherwise very good prognostic group. Our results provide support for the use of adjuvant trastuzumab in patients who are typically classified as having very good prognosis, not routinely offered standard chemotherapy, and who as such do not fit current UK prescribing guidelines for trastuzumab.

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer.

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (P

A review of the BIG results: the Breast International Group 1-98 trial analyses.

Patients treated surgically for early breast cancer show a peak recurrence 2 years following surgery. Distant metastases are the most common recurrence event and are associated with an increased risk of dying from breast cancer within 5 years. Consequently, reducing the risk of distant metastases is an important therapeutic goal. The use of an aromatase inhibitor (AI) as initial adjuvant therapy has been shown to reduce the risk of early recurrence. The Breast International Group 1-98 primary core analysis demonstrated that letrozole is the only AI in the initial adjuvant setting to demonstrate a significant 27% reduction in early distant metastases at 25.8 months in hormone receptor-positive patients. Once patients are diagnosed with distant metastases, they have incurable disease. Developing endocrine therapies to reduce the risk of distant metastases is, therefore, critically important therapeutic goal.

Evaluation of the relationship between the systemic inflammatory response and cancer-specific survival in patients with primary operable breast cancer.

The relationship between the systemic inflammatory response (as evidenced by elevated C-reactive protein and lowered albumin concentrations), clinico-pathologic status and relapse-free, cancer-specific and overall survival was examined in patients with invasive primary operable breast cancer (n=300). The median follow-up of the survivors was 46 months. During this period, 37 patients relapsed and 25 died of their cancer. On multivariate analysis, only tumour size (P<0.05), albumin (P<0.01) and systemic treatment (P<0.0001) were significant independent predictors of relapse-free, cancer-specific and overall survival. Lower serum albumin concentrations (

Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer.

Prediction of outcome in patients with metastatic breast cancer remains problematical. The present study evaluated the value of an inflammation-based score (Glasgow Prognostic Score, GPS) in patients with metastatic breast cancer. The GPS was constructed as follows: patients with both an elevated C-reactive protein (>10 mg l(-1)) and hypoalbuminaemia (<35 g l(-1)) were allocated a score of 2. Patients in whom only one or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. In total, 96 patients were studied. During follow-up 51 patients died of their cancer. On multivariate analysis of the GPS and treatment received, only the GPS (HR 2.26, 95% CI 1.45-3.52, P<0.001) remained significantly associated with cancer-specific survival. The presence of a systemic inflammatory response (the GPS) appears to be a useful indicator of poor outcome independent of treatment in patients with metastatic breast cancer.

The relationship between deprivation, tumour stage and the systemic inflammatory response in patients with primary operable breast cancer.

The extent of deprivation (Carstairs deprivation index) was directly associated with the magnitude of the systemic inflammatory response (reduced albumin and elevated C-reactive protein, P<0.01) in patients with primary operable breast cancer (n=314). Deprivation was not associated with age, tumour size, tumour type, grade, and the proportion of patients with involved lymph nodes and oestrogen receptor status.

Immediate breast reconstruction does not lead to a delay in the delivery of adjuvant chemotherapy.

Immediate breast reconstruction (IBR) has been considered by some to lead to a delay in the delivery of adjuvant chemotherapy. Our aim was to determine whether IBR led to a delay when compared to conservation surgery and non-reconstructive mastectomy. Ninety-five cases of IBR receiving chemotherapy were reviewed. These were compared to 95 consecutively treated patients undergoing conservation surgery and 95 undergoing non-reconstructive mastectomy. Our data shows that IBR does not lead to a delay in the delivery of adjuvant chemotherapy when compared to standard non-reconstructive surgery and should not adversely affect breast cancer outcome.