Preoperative prediction of margin requirement following a core biopsy result suggestive of a phyllodes tumour.

AIM: To determine if imaging features of lesions with a core biopsy suggestive of a phyllodes tumour can be used to identify which lesions require surgical excision with margins. MATERIALS AND METHODS: Thirty-one lesions were identified from a prospective database of ultrasound visible masses. Demographic, mammographic, and ultrasound features were assessed while blinded to surgical outcome. Features of those lesions requiring a margin and those that did not were compared. Statistical significance was established using the chi-square test and receiver operating characteristic (ROC) curves. RESULTS: Thirteen lesions (42%) required a margin and 18 lesions (58%) did not. Features found significantly more frequently in those requiring a margin were a poorly defined margin on mammography (7/9 [78%] versus 4/13 [31%]; p=0.04) and at ultrasound, an irregular margin (8/13 [62%] versus 3/18 [17%]; p=0.01), micro-lobulations (7/13 [54%] versus 3/18 [17%]; p=0.028), mixed echogenicity (9/13 [69%] versus 1/18 [6%]; p=0.0002), echogenic clefts (6/13 [46%] versus 1/18 [6%]; p=0.007), posterior enhancement (9/11 [82%] versus 6/18 [33%]; p=0.01), large size (p=0.003) and stiffness at shear-wave elastography (p=0.026). All six screen-detected lesions were benign. CONCLUSIONS: There are multiple preoperative features that can be used to guide surgical management of lesions with a preoperative core biopsy result suggestive of a phyllodes tumour.

Percutaneous sentinel node removal using a vacuum-assisted needle biopsy in women with breast cancer: a feasibility and acceptability study.

AIMS: To assess the feasibility and acceptability of large-gauge percutaneous removal of the axillary sentinel lymph node (SLN) using dual gamma probe and ultrasound guidance. MATERIALS AND METHODS: Technetium nanocolloid was administered the day before surgery. On the day of surgery, potential SLNs were identified with gamma probe and ultrasound scanning. A 7 G vacuum-assisted biopsy (VAB) device was inserted percutaneously deep to the target node and the node(s) removed. The gamma probe was used to confirm removal of radiolabelled tissue. At surgery, any residual radiolabelled or blue nodes were removed. Morbidity was assessed via (1) a pain questionnaire immediately after the percutaneous procedure, (2) relevant items from the FACT B+4 questionnaire 7-10 days after surgery, and (3) case note review 1 month after surgery. RESULTS: Twenty-two patients consented and 20 patients underwent the procedure. Radiolabelled nodal tissue was obtained in 18/20 (90%). The mean procedure time was 11 minutes. Four of 18 patients had metastatic disease identified in the VAB excision tissue with 100% sensitivity for axillary metastasis. At axillary surgery, additional intact SLN or fragments were found in 14 patients. No additional metastatic disease was found at surgery. One patient suffered a pneumothorax during instillation of local anaesthetic. The median pain score was 10/100 by visual analogue scale. Immediate post-procedure haematoma was common (14 of 20) and prolonged manual compression frequent. CONCLUSION: VAB removal of sentinel nodes using dual scanning is feasible. Although preliminary sensitivity and specificity levels are encouraging, complications may discourage widespread implementation.

Mutational mechanisms of amplifications revealed by analysis of clustered rearrangements in breast cancers.

Background: Complex clusters of rearrangements are a challenge in interpretation of cancer genomes. Some clusters of rearrangements demarcate clear amplifications of driver oncogenes but others are less well understood. A detailed analysis of rearrangements within these complex clusters could reveal new insights into selection and underlying mutational mechanisms. Patients and methods: Here, we systematically investigate rearrangements that are densely clustered in individual tumours in a cohort of 560 breast cancers. Applying an agnostic approach, we identify 21 hotspots where clustered rearrangements recur across cancers. Results: Some hotspots coincide with known oncogene loci including CCND1, ERBB2, ZNF217, chr8:ZNF703/FGFR1, IGF1R, and MYC. Others contain cancer genes not typically associated with breast cancer: MCL1, PTP4A1, and MYB. Intriguingly, we identify clustered rearrangements that physically connect distant hotspots. In particular, we observe simultaneous amplification of chr8:ZNF703/FGFR1 and chr11:CCND1 where deep analysis reveals that a chr8-chr11 translocation is likely to be an early, critical, initiating event. Conclusions: We present an overview of complex rearrangements in breast cancer, highlighting a potential new way for detecting drivers and revealing novel mechanistic insights into the formation of two common amplicons.

Identification of pathological complete response after neoadjuvant chemotherapy for breast cancer: comparison of greyscale ultrasound, shear wave elastography, and MRI.

AIM: To assess the value of post-treatment shear-wave elastography (SWE) parameters (maximum stiffness [Emax], mean stiffness [Emean], and standard deviation [SD]) compared to greyscale ultrasonography (US) and magnetic resonance imaging (MRI) in identifying pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer. MATERIALS AND METHODS: In a prospective cohort study, 80 patients receiving NACT for breast cancer underwent baseline and post-treatment US, SWE, and MRI examinations. Four SWE images in two orthogonal planes were obtained. Maximum greyscale US diameter and maximum diameter of lesion enhancement on MRI were measured. Percentage reductions between baseline and post-treatment scans were calculated for MRI and greyscale US diameter, and Emean, Emax, and SD. The percentage reduction in Emean and US diameter were also analysed as a combination. Analysis was undertaken using receiver operating characteristic (ROC) curves and the chi-squared test. RESULTS: pCR occurred in 21 of 80 (26%) women. The area under the ROC curve (AUC) for pCR of percentage reductions in Emean, Emax, SD, and greyscale US diameter were 0.89, 0.85, 0.75, and 0.86, respectively. The combination of percentage reductions in Emean and greyscale ultrasound diameter yielded an AUC of 0.92, which is similar to the AUC for MRI of 0.96 (p=0.28). CONCLUSIONS: SWE combined with greyscale US shows promise for end-of-treatment identification of response to NACT in women with breast cancer, with accuracies similar to breast MRI. This technique could be used to inform surgical decision-making after NACT.

Stiffness at shear-wave elastography and patient presentation predicts upgrade at surgery following an ultrasound-guided core biopsy diagnosis of ductal carcinoma in situ.

AIM: The aim of this study is to establish predictors of invasion in lesions yielding an ultrasound-guided biopsy diagnosis of ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: Patients subjected to ultrasound-guided core biopsy yielding DCIS were studied. At shear-wave elastography (SWE) a threshold of 50 kPa was used for mean elasticity (Emean) to dichotomise the elasticity data between invasive and non-invasive masses. Data recorded included the mammographic and ultrasound features, the referral source, and grade of DCIS in the biopsy. The chi-square test was used to detect statistical significance. RESULTS: Of 57 lesions, 24 (42%) had invasion at excision. Symptomatic patients and patients with stiff lesions were more likely to have invasion than patients presenting through screening and with soft lesions (58% [14 of 24] versus 30% [10 of 33], p=0.03) and (51% [20 of 39] versus 22% [4 of 18], p=0.04). No other factors showed a relationship with invasion. Combining the two predictors of invasion improved risk stratification with symptomatic and stiff lesions having a risk of invasion of 67% (12 of 18) and soft lesions presenting at screening having only a 17% (2 of 12) risk of invasion (p=0.02). CONCLUSION: Stiffness on SWE and the referral source of the patient are predictors of occult invasion in women with an ultrasound-guided core biopsy diagnosis of DCIS.

Viewpoint: Availability of oestrogen receptor and HER2 status for the breast multidisciplinary meeting discussion; time to get it right.

The efficacy and pivotal role of the multidisciplinary meeting (MDM) in informed decision making is well established. It aims to provide a forum in which clinical evidence combines with individual patient data to create a personalized treatment plan. It does not fulfil this role adequately when undertaken without the full results of the patient's investigations being available. Neither doctor nor patient can make an informed decision about treatment options without knowledge of the tumour receptor status. Both targeted therapies and the aim to treat a majority of patients within clinical trials must now drive MDM decision making to be based on accuracy and best available treatment choices. A fully informed decision on treatment delayed by 1-2 weeks is clearly preferable to rushed time target-driven decisions made without the patient being offered a fully informed choice as ratified by a multidisciplinary team. Whilst the early anxiety of waiting for all relevant information to be available may be stressful for patients, not being sure that they have been offered fully informed treatment choices is also stressful and could cause longer lasting anxiety both during and after treatment. MDMs need to develop (along with targeted therapies) to retain their role as a forum whereby patients receive a correct, but specifically a full diagnosis and allow a fully informed discussion of all treatment options, including pre-operative clinical trials.

Magnetic resonance imaging texture analysis classification of primary breast cancer.

OBJECTIVES: Patient-tailored treatments for breast cancer are based on histological and immunohistochemical (IHC) subtypes. Magnetic Resonance Imaging (MRI) texture analysis (TA) may be useful in non-invasive lesion subtype classification. METHODS: Women with newly diagnosed primary breast cancer underwent pre-treatment dynamic contrast-enhanced breast MRI. TA was performed using co-occurrence matrix (COM) features, by creating a model on retrospective training data, then prospectively applying to a test set. Analyses were blinded to breast pathology. Subtype classifications were performed using a cross-validated k-nearest-neighbour (k = 3) technique, with accuracy relative to pathology assessed and receiver operator curve (AUROC) calculated. Mann-Whitney U and Kruskal-Wallis tests were used to assess raw entropy feature values. RESULTS: Histological subtype classifications were similar across training (n = 148 cancers) and test sets (n = 73 lesions) using all COM features (training: 75%, AUROC = 0.816; test: 72.5%, AUROC = 0.823). Entropy features were significantly different between lobular and ductal cancers (p < 0.001; Mann-Whitney U). IHC classifications using COM features were also similar for training and test data (training: 57.2%, AUROC = 0.754; test: 57.0%, AUROC = 0.750). Hormone receptor positive and negative cancers demonstrated significantly different entropy features. Entropy features alone were unable to create a robust classification model. CONCLUSION: Textural differences on contrast-enhanced MR images may reflect underlying lesion subtypes, which merits testing against treatment response. KEY POINTS: • MR-derived entropy features, representing heterogeneity, provide important information on tissue composition. • Entropy features can differentiate between histological and immunohistochemical subtypes of breast cancer. • Differing entropy features between breast cancer subtypes implies differences in lesion heterogeneity. • Texture analysis of breast cancer potentially provides added information for decision making.

What are the characteristics of breast cancers misclassified as benign by quantitative ultrasound shear wave elastography?

OBJECTIVES: Shear wave elastography (SWE) is a promising adjunct to greyscale ultrasound in differentiating benign from malignant breast masses. The purpose of this study was to characterise breast cancers which are not stiff on quantitative SWE, to elucidate potential sources of error in clinical application of SWE to evaluation of breast masses. METHODS: Three hundred and two consecutive patients examined by SWE who underwent immediate surgery for breast cancer were included. Characteristics of 280 lesions with suspicious SWE values (mean stiffness >50 kPa) were compared with 22 lesions with benign SWE values (<50 kPa). Statistical significance of the differences was assessed using non-parametric goodness-of-fit tests. RESULTS: Pure ductal carcinoma in situ (DCIS) masses were more often soft on SWE than masses representing invasive breast cancer. Invasive cancers that were soft were more frequently: histological grade 1, tubular subtype, ≤10 mm invasive size and detected at screening mammography. No significant differences were found with respect to the presence of invasive lobular cancer, vascular invasion, hormone and HER-2 receptor status. Lymph node positivity was less common in soft cancers. CONCLUSION: Malignant breast masses classified as benign by quantitative SWE tend to have better prognostic features than those correctly classified as malignant. KEY POINTS: • Over 90 % of cancers assessable with ultrasound have a mean stiffness >50 kPa. • 'Soft' invasive cancers are frequently small (≤10 mm), low grade and screen-detected. • Pure DCIS masses are more often soft than invasive cancers (>40 %). • Large symptomatic masses are better evaluated with SWE than small clinically occult lesions. • When assessing small lesions, 'softness' should not raise the threshold for biopsy.

CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.

Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study.

BACKGROUND: Progesterone receptor (PR) expression assessment in early invasive breast cancer remains controversial. This study sought to re-evaluate PR expression as a potential therapeutic guide in early breast cancer; particularly in oestrogen receptor (ER)-positive, lymph node (LN)-negative disease. METHODS: A population cohort of 1074 patients presenting to a single Cancer Centre over 4 years (2000-2004) underwent surgery for primary invasive breast cancer with curative intent. Prospective data collection included patient demographics, pathology, ER and PR expression, HER2 status, adjuvant chemotherapy and endocrine therapy. Progesterone receptor expression was compared with (all causes) overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS). RESULTS: Overall survival was 71.0% and BCSS was 83.0% at median follow-up of 8.34 years. Absent PR expression was significantly associated with poorer prognosis for OS, BCSS and DFS (P<0.0001, log-rank), even within the ER-positive, LN-negative group (hazard ratio for BCSS 3.17, 95% CI 1.43-7.01) and was not influenced by endocrine therapy. Cox's regression analysis demonstrated that PR expression was an independent prognostic variable. CONCLUSION: Absence of PR expression is a powerful, independent prognostic variable in operable, primary breast cancer even in ER-positive, LN-negative patients receiving endocrine therapy. Absence of PR expression should be re-evaluated as a biomarker for poor prognosis in ER-positive breast cancer and such patients considered for additional systemic therapy.

HER2 testing for breast carcinoma: recommendations for rapid diagnostic pathways in clinical practice.

Human epidermal growth factor receptor 2 (HER2) testing is required for newly diagnosed breast cancer and advised for recurrent and metastatic breast cancer, to determine treatment planning using HER2-directed therapy in the neoadjuvant, adjuvant and advanced disease settings. Wide variation, nationally, in the turnaround time for HER2 testing may hinder equity of access for patients to both clinical trials and the timely implementation of HER2-directed therapy particularly in the neo-adjuvant setting. Process mapping from three recognised laboratories in the UK was applied to the logistics of HER2 testing in different geographic hub and spoke models. Consequently, recommendations for HER2 testing likely to facilitate access to clinical trials and timely patient care are presented.

Can shear-wave elastography predict response to neoadjuvant chemotherapy in women with invasive breast cancer?

BACKGROUND: Response of invasive breast cancer to neoadjuvant chemotherapy (NAC) is variable, and prediction of response is imperfect. We aimed to ascertain whether tissue stiffness in breast cancers, as assessed by shear-wave elastography (SWE) before treatment, is associated with response. METHODS: We retrospectively compared pre-treatment tumour mean tissue stiffness, with post-treatment Residual Cancer Burden (RCB) scores and its components in 40 women with breast cancer treated by NAC using Pearson's correlation coefficient (CC), a general linear model and multiple linear regression. Subgroup analysis was carried out for luminal, HER2-positive and basal immuno-histochemical subtypes. RESULTS: Statistically significant correlations were shown between stiffness and RCB scores and between stiffness and percentage tumour cellularity. The correlation between stiffness and percentage cellularity was strongest (CC 0.35 (P<0.0001) compared with CC 0.23 (P=0.004) for the RCB score). The results of a general linear model show that cellularity and RCB score maintain independent relationships with stiffness. By multiple linear regression, only cellularity maintained a significant relationship with stiffness. CONCLUSION: Pre-treatment tumour stiffness measured by SWE, has a statistically significant relationship with pathological response of invasive breast cancer to NAC.

Clinical value of internal mammary lymph node metastases found incidentally during free flap recipient vessel exposure.

INTRODUCTION: The clinical importance of internal mammary (IM) lymph node (LN) metastases in breast cancer remains unclear. The aim of this study was to determine the clinical value of opportunistic IMLN sampling at the time of free flap breast reconstruction using the IM recipient vessels and whether it affected the adjuvant treatment given. METHODS: A prospective study was conducted of IMLN exploration performed by a single surgeon as part of free flap breast reconstruction using IM recipient vessels. Patients where IMLNs were positive for metastatic disease were reviewed with the breast cancer multidisciplinary team for changes in therapy. RESULTS: 122 patients met the inclusion criteria, 111 of whom had immediate reconstructions. 63 patients had IMLNs excised, and of these 13 were positive for metastatic disease, all in immediate breast reconstructions. The adjuvant treatment given was changed in 1 patient with no axillary LN disease as a result of finding a positive IMLN. Positive IMLNs were significantly associated with larger tumours and axillary metastases, but not tumour location. All patients with positive IMLNs were alive at last follow-up with no local or distant recurrences, with mean disease-free survival of 20.5 months (5-56 months). CONCLUSION: Incidental IMLNs positive for metastatic disease were found in 13 of 122 free flap breast reconstructions and resulted in a change in adjuvant treatment in one patient. IMLNs found incidentally during recipient IM vessel exposure for free flap breast reconstruction therefore may upstage a patient's disease and influence the adjuvant treatment for their breast cancer and should therefore be submitted for pathological assessment.

Can additional histopathological examination of ultrasound-guided axillary lymph node core biopsies improve preoperative diagnosis of primary breast cancer nodal metastasis?

AIM: To assess whether an additional histopathological examination of ultrasound-guided core biopsy (USCB)/fine-needle aspiration (FNA) of abnormal axillary lymph nodes (ALN) can improve the preoperative diagnosis of axillary nodal metastasis. MATERIALS AND METHODS: Women with suspected invasive breast cancer and abnormal axillary ultrasound (AUS), but negative USCB on standard histopathological assessment were included. From the core biopsies six additional levels were sectioned for haematoxylin and eosin examination, and two levels were sectioned for immunohistochemistry with AE1/3. The presence of metastatic disease was noted. RESULTS: The USCB of 102 patients were submitted for additional histopathological examination, of whom 58 had screen-detected lesions and 44 had symptomatic lesions. Eighty underwent axillary surgery for invasive carcinoma (n = 74) or for ductal carcinoma in situ (DCIS) requiring mastectomy (n = 6). Twelve patients were found to have nodal disease with a mean of two nodes involved. The additional histopathological assessment of the nodal USCBs revealed tumour not seen at the standard examination in only three cases, which consisted of isolated tumour cells (n = 2) and micrometastasis (n = 1). All three patients underwent subsequent axillary node clearance; however, no upgrade of axillary disease was found at final histopathology. CONCLUSION: Additional histopathological examination of USCBs of radiologically abnormal ALN does not improve the preoperative diagnosis of axillary nodal metastasis in primary breast cancer and may lead to unnecessary axillary clearance.

Multiparameter DNA content analysis identifies distinct groups in primary breast cancer.

BACKGROUND: Multiparameter flow cytometry is a robust and reliable method for determining tumour DNA content applicable to formalin-fixed paraffin-embedded (FFPE) tissue. This study examined the clinical and pathological associations of DNA content in primary breast cancer using an improved multiparametric technique. METHODS: The FFPE tissue from 201 primary breast cancers was examined and the cancers categorised according to their DNA content using multiparametric flow cytometry incorporating differential labelling of stromal and tumour cell populations. Mathematical modelling software (ModFit 3.2.1) was used to calculate the DNA index (DI) and percentage S-phase fraction (SPF%) for each tumour. Independent associations with clinical and pathological parameters were sought using backward stepwise Binary Logistic Regression (BLR) and Cox's Regression (CR) analysis. RESULTS: Tumours were grouped into four categories based on the DI of the tumour cell population. Low DI tumours (DI=0.76-1.14) associated with progesterone receptor-positive status (P=0.012, BLR), intermediate DI (DI=1.18-1.79) associated with p53 mutant tumours (P=0.001, BLR), high DI (DI1.80) tumours with human epidermal growth factor receptor 2 (HER2)-positive status (P=0.004, BLR) and 'multiploid tumours' (two or more tumour DNA peaks) did not show any significant associations. Tumours with high SPF% (10%) independently associated with poor overall survival (P=0.027, CR). CONCLUSION: Multiparametric flow analysis of FFPE tissue can accurately assess tumour DNA content. Tumour sub-populations associated with biomarkers of prognosis or likely response to therapy. The alterations in DNA content present the potential for greater understanding of the mechanisms underlying clinically significant biomarker changes in primary breast cancer.

Differentiating benign from malignant solid breast masses: value of shear wave elastography according to lesion stiffness combined with greyscale ultrasound according to BI-RADS classification.

BACKGROUND: The aim of this study was to assess the performance of shear wave elastography combined with BI-RADS classification of greyscale ultrasound images for benign/malignant differentiation in a large group of patients. METHODS: One hundred and seventy-five consecutive patients with solid breast masses on routine ultrasonography undergoing percutaneous biopsy had the greyscale findings classified according to the American College of Radiology BI-RADS. The mean elasticity values from four shear wave images were obtained. RESULTS: For mean elasticity vs greyscale BI-RADS, the performance results against histology were sensitivity: 95% vs 95%, specificity: 77% vs 69%, Positive Predictive Value (PPV): 88% vs 84%, Negative Predictive Value (NPV): 90% vs 91%, and accuracy: 89% vs 86% (all P>0.05). The results for the combination (positive result from either modality counted as malignant) were sensitivity 100%, specificity 61%, PPV 82%, NPV 100%, and accuracy 86%. The combination of BI-RADS greyscale and shear wave elastography yielded superior sensitivity to BI-RADS alone (P=0.03) or shear wave alone (P=0.03). The NPV was superior in combination compared with either alone (BI-RADS P=0.01 and shear wave P=0.02). CONCLUSION: Together, BI-RADS assessment of greyscale ultrasound images and shear wave ultrasound elastography are extremely sensitive for detection of malignancy.

Sentinel node biopsy in breast cancer has a greater node positivity rate than axillary node sample: results from a retrospective analysis.

BACKGROUND: Sentinel node biopsy as a surgical method of axillary staging for early breast cancer has been widely accepted as an alternative to traditional four-node axillary node sampling, and is the recommended technique by the Association of Breast Surgery in the United Kingdom. In selected units axillary sampling has been compared with either radioisotope sentinel node or blue dye only techniques with comparable node positivity rates. There are no studies directly comparing combined method sentinel node biopsy (SNB) with conventional axillary (four) node sampling (ANS). METHODS: Data for all patients undergoing axillary staging by axillary node sample or sentinel node biopsy were collected, including those proceeding to axillary clearance as a second procedure, but excluding those undergoing axillary clearance as a first procedure. RESULTS: From January 2005 to January 2011, 641 axillary staging procedures were performed (SNB n=231 (36.0%), ANS n=410 (64.0%)). Baseline tumour characteristics were similar for the two groups except for a higher frequency of breast conservation in the SNB group (95.6 vs. 75.6%; p<0.0001). The proportion of cases with positive nodes was higher in the SNB group (20.8 vs. 14.4%; p=0.042). In patients who had presented with symptomatic disease, there was a significantly higher node positivity rate with SNB (30.9%) than with ANS (15.5%; p=0.002), despite similar baseline characteristics in both groups. CONCLUSION: Combined method sentinel node biopsy is more sensitive at detecting low volume axillary disease than traditional four-node sample.

Involved anterior margins after breast conserving surgery: is re-excision required?

BACKGROUND: Complete tumour excision in breast conserving surgery (BCS) is critical for successful outcome; involved circumferential resection margins are associated with increased disease recurrence. However, the importance of an involved anterior margin (IAM) is less clear. The purpose of this study was to review an aggressive approach to IAM and hence assess whether anterior margin re-excision (RE) yields clinical benefit. METHODS: A review of prospectively collected clinical and pathology data was performed for all patients who underwent BCS between 2006 and 2010 through a single cancer centre. An involved margin was defined as < 1 mm clearance of invasive or in-situ breast cancer. RESULTS: 1667 patients underwent BCS for invasive and/or in-situ disease, of whom 114 underwent RE. A total of 170 involved margins were identified: most commonly the anterior (52 margins) followed by the posterior (39 margins) and inferior (31 margins) margin. Patients with IAM were more likely to have grade 3 invasive disease (p = 0.0323) but less likely to have residual disease found at re-excision (2/49 vs. 32/101 margins, p = 0.0033); there were no differences when in-situ characteristics were compared. CONCLUSIONS: RE of IAM after BCS rarely yields further disease; multi-disciplinary teams should consider whether further therapy for an IAM is required on a patient by patient basis.

Axillary lymph node core biopsy for breast cancer metastases -- how many needle passes are enough?

AIM: To determine the diagnostic yield of each of three core passes when sampling abnormal lymph nodes in patients presenting with breast cancer. MATERIALS AND METHODS: All patients suspected of having breast cancer had axillary ultrasound as part of initial assessment. Radiologically abnormal nodes (cortical thickness >2.3mm or round shape) were biopsied with three passes of a 22 mm throw 14 G core biopsy needle and sent for histopathology in separate numbered pots. Data were collected prospectively, and analysis performed on the data of 55 consecutive patients who had positive nodes on at least one core biopsy needle pass. RESULTS: Of 55 patients with a positive node on core biopsy, tumour was noted in all three cores taken in 39 (70.9%). Lymph node metastasis was detected in 45 (81.8%) first core biopsies. With the first two cores taken, positive results were detected in 53 of 55 cases (96.4%). In both cases where tumour was only found on a third core biopsy pass, no lymph node tissue was present in the first two biopsy passes. CONCLUSION: Two well-directed 14 G core biopsy samples from an abnormal axillary node are adequate for diagnosis of breast cancer metastasis.

High frequency of complex TP53 mutations in CNS metastases from breast cancer.

BACKGROUND: Brain metastasis from breast cancer is usually associated with a poor prognosis and early death. Alteration of p53 may contribute to malignant progression by abrogation of apoptosis induced by oncogene activation and by acquisition of gain-of-function properties, which promote tumour aggression. Mutation in TP53 occurs at high frequency in carcinomas of the lung and gastro-intestinal tract, but is much less frequent, at 25%, in primary breast cancer. The frequency of TP53 alteration in the central nervous system (CNS) metastatic breast cancer is not known. METHODS: In all, 23 cases of histologically confirmed CNS metastatic breast cancer were identified and the coding sequence of TP53 determined. TP53 was also sequenced in two control series of primary breast carcinomas from independent clinical centres. RESULTS: We demonstrate a strikingly high frequency of TP53 mutation in the CNS metastatic lesions with an over-representation of complex mutations (non-sense/deletions/insertions). Complex mutations occur in metastatic lesions in both triple-negative breast cancer and hormone receptor/HER2-positive cases. Analysis of paired primary carcinomas and brain metastatic lesions revealed evidence for both clonal selection and generation of new mutations (missense and complex) in progression from a primary breast carcinoma to brain metastasis. CONCLUSION: Mutation in TP53 is the most common genetic alteration reported during metastasis to the brain in breast cancer.