Complete excision with narrow margins provides equivalent local control to wider excision in breast conservation for invasive cancer.

Background: Society of Surgical Oncology and American Society for Radiation Oncology guidelines define clear margins in breast-conserving therapy (BCT) as 'no ink on tumour', in contrast to the attainment of margins of at least 1 mm widely practised in the UK. The primary aim of this study was to explore clinical, surgical and tumour-related factors associated with local recurrence after BCT, with a secondary aim of assessing the impact of margin re-excision on the risk of local recurrence. Methods: Patient demographics, surgical details, tumour characteristics and local recurrence were recorded for consecutive women with BCT undergoing surgery between January 1997 and January 2007. Margins were defined as clear (greater than 1 mm), close (less than 1 mm but no ink on tumour), reaches (ink on tumour) and clear after re-excision. Results: A total of 1045 women of median age 54 (range 18-86) years were studied. Median follow-up was 89 (range 4-196) months. Local recurrence occurred in 52 patients (5·0 per cent). Ink on tumour was associated with local recurrence (hazard ratio (HR) 4·86, 95 per cent c.i. 1·49 to 15·79; P = 0·009). Risk of local recurrence was the same for close and clear margins (HR 1·03, 0·40 to 2·62; P = 0·954). In women with involved margins, re-excision was still associated with an increased local recurrence risk (HR 2·50, 1·32 to 4·72; P = 0·005). Oestrogen receptor negativity increased risk (HR 2·28, 1·28 to 4·06; P = 0·005). Conclusion: Adequately excised margins, even when under 1 mm, provide equivalent outcomes to wider margins in BCT. Achieving complete excision at primary surgery achieves the lowest rates of local recurrence.

Aesthetic and oncologic outcomes after one-stage immediate breast reconstruction using a permanent biodimensional expandable implant.

INTRODUCTION: Immediate breast reconstruction (IBR) with implants is the commonest method of reconstructive surgery after mastectomy. With careful patient selection, a stable implant pocket can be created at the primary operation to decrease the likelihood of further surgery to adjust the reconstructed side. One-stage IBR is cost effective but failed procedures requiring early revision may be costly as permanent expanders are expensive. METHODS: Data were prospectively collected on all women undergoing a planned one-stage immediate breast reconstruction between 1997 and 2010. All patients had a Style 150 implant (Allergan, Marlow, UK). Descriptive statistics, Kaplan-Meier plots and, where applicable, Cox Proportional Hazards Regression was used to compare outcomes between groups. RESULTS: 249 planned one-stage IBRs were performed in 193 women, median age 45 years (range 20-77) with median follow-up of 101 months (range 27-159 months). 18/193 (9%) patients required implant exchange at 12 months and 66% of patients maintained their original implants at the time of census. Implant assisted latissimus appears to be robust even when radiotherapy was delivered. Disease free survival and breast cancer mortality were as expected for the breast cancer stage treated. CONCLUSION: With careful patient selection, one-stage implant IBR using a definitive anatomical expandable implant provides good long term reconstruction and safe oncologic outcome. Direct to implant decision algorithms may be influenced by future developments in acellular dermal matrix technology, but the ability to create a single-stage stable implant pocket with good surgical technique should not be forgotten.

In vivo study of the surgical anatomy of the axilla.

BACKGROUND: Classical anatomical descriptions fail to describe variants often observed in the axilla as they are based on studies that looked at individual structures in isolation or textbooks of cadaveric dissections. The presence of variant anatomy heightens the risk of iatrogenic injury. The aim of this study was to document the nature and frequency of these anatomical variations based on in vivo peroperative surgical observations. METHODS: Detailed anatomical relationships were documented prospectively during consecutive axillary dissections. Relationships between the thoracodorsal pedicle, course of the lateral thoracic vein, presence of latissimus dorsi muscle slips, variations in axillary and angular vein anatomy, and origins and branching of the intercostobrachial nerve were recorded. RESULTS: Among a total of 73 axillary dissections, 43 (59 per cent) revealed at least one anatomical variant. Most notable variants included aberrant courses of the thoracodorsal nerve in ten patients (14 per cent)--three variants; lateral thoracic vein in 12 patients (16 per cent)--four variants; bifid axillary veins in ten patients (14 per cent); latissimus dorsi muscle slips in four patients (5 per cent); and variants in intercostobrachial nerve origins and branching in 26 patients (36 per cent). The angular vein, a subscapular vein tributary, was found to be a constant axillary structure. CONCLUSION: Variations in axillary anatomical structures are common. Poor understanding of these variants can affect the adequacy of oncological clearance, lead to vascular injury, compromise planned microvascular procedures and result in chronic pain or numbness from nerve injury. Surgeons should be aware of the common anatomical variants to facilitate efficient and safe axillary surgery.

Nipple-sparing mastectomy.

BACKGROUND: Although effective local control is the primary goal of surgery for breast cancer, the long-term aesthetic outcome is also important. Nipple-sparing mastectomy aims to address this, but there is no consensus on its clinical application. Evidence relating to oncological safety, surgical technique and early data on aesthetic outcome was reviewed. METHODS: The review was based on a PubMed search using the terms 'nipple-sparing' or 'subcutaneous mastectomy' and 'breast cancer'. RESULTS: Large pathological studies report occult nipple involvement with cancer in 5.6-31 per cent, reflecting variation in inclusion criteria. Recent clinical series with careful patient selection report local recurrence in less than 5 per cent of patients. The incidence of cancer in the retained nipple after risk-reducing mastectomy is less than 1 per cent. Nipple necrosis rates range up to 8 and 16 per cent for total and partial necrosis respectively. Variations in outcome result from differences in extent of resection, placement of incisions and type of breast reconstruction. CONCLUSION: Nipple-sparing mastectomy is an acceptable technique for women undergoing risk-reducing mastectomy. In the therapeutic setting, it may be offered to patients with smaller tumours far from the nipple and favourable pathological features. Women should be counselled about nipple necrosis and the potential for local recurrence.

A comparative proteinomic analysis of nipple aspiration fluid from healthy women and women with breast cancer.

This pilot study examines the feasibility of nipple aspiration to distinguish women with breast cancer from healthy women using surface-enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF/MS). Nipple aspiration fluid (NAF) was collected from each breast in 21 women newly diagnosed with unilateral breast cancer and 44 healthy women. No differences were found when proteomic profiles of NAF from the cancer-bearing breast and the contralateral non-cancerous breast were compared. In contrast, 9 protein peaks were significantly different between the cancer-bearing breast compared with healthy women and 10 peaks were significantly different between the contralateral healthy breast and healthy women (P<0.05). These data suggest that invasive breast cancer may result in a field change across both breasts and that proteomic profiling of NAF may have more value in breast cancer risk assessment than as a diagnostic or screening tool.

The influence of radiotherapy on capsule formation and aesthetic outcome after immediate breast reconstruction using biodimensional anatomical expander implants.

BACKGROUND: Capsular contracture occurs more frequently when immediate breast reconstruction (IBR) is associated with radiotherapy (RT) in a post-mastectomy field. The aim of this study was to investigate the impact of RT on surgical outcome after IBR using a single implant type. METHODS: One hundred and thirty-six breast reconstructions were studied in 114 patients: 62 reconstructions were performed using submuscular implants alone and 74 had an implant-assisted latissimus dorsi myocutaneous flap using a McGhan 150 biodimensional permanent expander implant. Data were prospectively collected on capsule contracture, geometric measurements, photographic assessments and pain scores. The median follow-up was 4 (range, 2-5) years. RESULTS: The mean age of the 114 patients studied was 45 (range, 20-77) years. Forty-four reconstructed breasts received RT. Capsule formation was detected in 13/92 (14.1%) reconstructed breasts with no RT and in 17/44 (38.6%) reconstructed breasts with RT. On univariate analysis, RT was the only variable related to capsule formation (p<0.001). Significant differences in geometric measurements of symmetry were identified in patients with capsules compared with those without capsules. Photographic assessments were worse in the capsule group: mean photo score 8 (95% CI 8, 8.5) compared with the no capsule group 6.5 (95% CI 5, 7.5), p<0.001. Persistent pain two years or more after surgery was present in 8/30 patients with capsules and 1/106 with no capsule group, p<0.01. Capsule formation is three times more likely to occur after IBR in association with an RT field. However, as more than 60% of patients do not get capsules despite RT at four years, implant-assisted tissue expansion techniques using a biodimensional device is a viable breast reconstructive option in selected cases.

Clinical outcome and service implications of screening women at increased breast cancer risk from a family history.

INTRODUCTION: The value of special screening for women at moderate breast cancer risk with a family history of breast cancer remains controversial. Little is known about recall rates, false negative outcomes and the impact on clinical service. Despite this, surveillance programmes within breast units have been established in the United Kingdom. PATIENTS AND METHODS: In our institution, screening of women at moderate (lifetime risk, 17-30%) and high risk (>30%) consisted of annual clinical examination and mammography from the age of 35 years. The active study period ran for four months and each patient was followed through a further screening cycle (whole study period), providing information on interval cancers and detection at the subsequent screen. RESULTS: One thousand one hundred and thirty-two women attended for their incident screen: 137 at high risk, 803 at moderate risk and 192 at standard risk. The median age at cancer diagnosis in the moderate risk group was 54 (range, 45-68) years and the high-risk group 51 (46-52) years, compared to 63 (45-69) years in the standard risk group. Seven cancers were diagnosed during the four-month active study period. Two patients were diagnosed with interval cancers and eight at the next screen, giving a cancer incidence in the whole study period of 17/1132 (1.5%). Thirteen patients had invasive cancer and four had ductal carcinoma in situ (DCIS) The median invasive tumour size was 15 had (range, 7-28)mm and the median DCIS size was 4 (2-30)mm. 10/13 (76.9%) invasive cancers were < or =20mm and 2/13 patients (15.4%) with invasive cancer were lymph node positive. The sensitivity and specificity of mammography were 85.7% and 98.8%, respectively. The mammogram recall rate was 27.6 per 1000. The benign to malignant surgery ratio was 8:17. CONCLUSION: Screening women at increased breast cancer risk is effective. Early detection and recall rates are comparable to that of older women attending the British National Breast Screening Programme.

Wire localisation biopsy of non-palpable breast lesions: reasons for unsuccessful excision.

Surgical excision following needle-wire localization of nonpalpable, mammographically detected breast lesions is a very valuable diagnostic and therapeutic procedure. No further treatment is usually required after establishing an accurate histological benign diagnosis of indeterminate lesions on preoperative assessment. On the other hand, ductal carcinoma in-situ (DCIS) and early invasive cancer, properly excised, may sometimes require further management depending on specific histologic findings. An uncommon problem of this procedure is the failure to identify, localize or excise the breast lesion. In this review article, factors that contribute to the failed needle localization procedure are presented.

Endothelial adhesion molecules in breast cancer invasion into the vascular and lymphatic systems.

AIMS: It is well recognised that intravasation of tumour cells into the vasculature and/or lymphatics is a key stage in the metastatic process. It is also clear that very little is known about the mechanisms underlying this event. In this review, we will focus on cell surface molecules that may be instrumental in mediating the attachment of tumour cells, and in particular breast carcinoma cells, to the lymphatic and microvascular endothelia and discuss the therapeutic and prognostic value in targeting these receptors in metastatic disease. METHODS: A literature search was carried out from PubMed for indexed articles and reviews. Websites containing information on gene expression profiles were located using standard web browser search functions. For articles containing gene expression data, relevant information was frequently located in supplementary tables or in associated websites. FINDINGS: The search yielded a very large number of indexed published articles and websites. Important major reports and studies were reviewed, screened and tracked for other relevant publications. The most important articles were analysed and discussed. CONCLUSIONS: The lack of knowledge as to the mechanism by which tumour cells intra-vasate into the vasculature and/or lymphatics is perhaps not surprising given the lack of suitable models with which to investigate tumour cell intravasation. However, recent advances in the identification of molecular markers of angiogenic and lymphangiogenic endothelium, the development of techniques to image tumour cells in vivo and a better understanding of the architecture of these vessels is beginning to offer hope that this least well understood event in the metastatic process is becoming more amenable to study.

Continued axillary sampling is unnecessary and provides no further information to sentinel node biopsy in staging breast cancer.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) has become increasingly accepted as a diagnostic method to stage the axilla in breast cancer, selecting women with a positive sentinel node for completion axillary clearance. As SLNB became established, many surgeons supplemented SLNB to sample a minimum of four lymph nodes, on the assumption that the four-node technique is supported by randomised trial data. We hypothesised that the practice of undirected sampling to supplement SLNB adds little information to the status of the residual axilla. METHODS: One hundred and sixty-five patients with early breast cancer were studied. Following successful identification of the sentinel node, 84 women had completion axillary dissection and 81 women had an axillary sample with at least four nodes available for pathological assessment. RESULTS: Following successful identification of the sentinel node in 165 patients, the false negative rate (FNR) was 2/44=4.5% (95% CI 0.6-15.5), sensitivity 42/44=95.5% (84.5-99.4) and negative predictive value (NPV) 121/123=98.4% (94.2-99.8). In the axillary dissection cohort, the FNR was 2/26=7.7% (0.9-25.1), sensitivity 24/26=92.3% (74.9-99.1) and NPV 58/60=96.7% (88.5-100). In the axillary sample group, the FNR was 0/18=0% (0-18.5), sensitivity 18/18=100% (81.5-100) and NPV 63/63=100% (94.3-100). The SLNB was the only positive node in 12/26 (46.2%) in the axillary dissection group and 10/18 (55.6%) in the axillary sampling group. There was no patient in the axillary sampling group where the sample node was positive and the sentinel node negative. CONCLUSION: Once SLNB is validated within the multidisciplinary unit, undirected sampling of the axilla following identification of the sentinel node(s) is unnecessary. The additional sampling of non-sentinel nodes has no role to play either in the assessment of a potential false negative SLNB nor as predictive information on the status of the residual axillary nodes.

Factors predisposing to cavity margin positivity following conservation surgery for breast cancer.

AIMS: Incomplete excision leads to local recurrence following breast conservation therapy (BCT). The aim of this study was to examine factors associated with cavity margin (CM) positivity and return to theatre rates. METHODS: Breast conservation surgery with entire CM excision was the initial procedure in 301 patients with 303 breast cancers. Of these, 258 patients were treated successfully with breast conservation surgery and 43 patients subsequently required a mastectomy for persistent involved margins. The mean and median follow-up was 38 and 42 (range 6-78) months, respectively. RESULTS: Positive CMs were found in 73 out of 303 tumours. Large tumour size (p<0.001) and tumour type (invasive lobular cancer and ductal carcinoma in-situ) (p=0.043) were significant predictors of CM positivity both by univariate and multivariate analysis. As a result of CM status in relation to initial margin (IM) status, 60 cancers treated that were IM positive but CM negative avoided return for further excision at a second operative procedure. CONCLUSION: Complete CM excision should avoid the need for further re-excision surgery in most patients where initial specimen margin was positive.

Integrin expression and survival in human breast cancer.

BACKGROUND: Integrin cell adhesion molecules are fundamental to numerous cellular functions including anchorage, differentiation and proliferation. Reduced expression of certain alpha and beta integrin subunits in primary breast cancer cells has been correlated with increased invasion and metastasis. Conversely, over-expression of the alpha6 subunit has been linked to poorer survival. The objective of this study was to measure the survival of a cohort with breast carcinoma in relation to integrin expression and to evaluate their potential as prognostic indicators. METHOD: Integrin expression on samples from 99 consecutive patients with breast cancer was assayed using monoclonal antibodies to the subunits alpha(1,2,3,6,V) and beta(1,3,4,5). This cohort has now been followed prospectively for almost five years allowing for early assessment of survival in relation to integrin expression. RESULTS: Whilst analysis of the data confirmed the relation of survival to proven predictors of tumour grade, tumour size and vascular invasion, statistical significance was not demonstrated with regard to both lymph node status and all integrin subunits studied. CONCLUSION: Previous research correlating certain integrin subunits with survival has not been confirmed in this study. Despite proven molecular importance in tumour cell adhesion, invasion and metastasis, integrin expression would appear not to translate clinically as independent indicators of prognosis, at least in the short-term.

Clinical presentation and long-term outcome of pure myoepithelial carcinoma of the breast.

INTRODUCTION: Pure myoepithelial carcinoma of the breast is a rare tumour of controversial histogenesis. Little is known about its natural history and long-term outcome following treatment. METHODS: All patients with pure myoepithelial carcinoma treated at our institution between 1970 and 2001 were studied with respect to pathological features, outcome and prognosis. RESULTS: Six patients were identified. The median age was 60 (40-66) years and median follow-up was 34.5 months (range 14-76) months. Four tumours were T1 and one was T2 (one tumour size unknown). There were two moderately differentiated and three well-differentiated tumours (grade could not be assessed in one patient). Oestrogen and progesterone receptor could be assessed in five patients and all were negative. Primary treatment was wide local excision with clear radial margins. Lymph node assessment was negative in all patients. One patient received adjuvant radiotherapy. Three patients developed local recurrence at 15, 38 and 50 months and two patients developed distant metastasis at 30 and 79 months. The local recurrences were treated by further excision but two patients developed distant metastasis at intervals of 15 and 26 months, respectively. Two patients have died of the disease and four remain well. The 2-year and 5-year survival was 88% (SE, 6) and 55% (SE, 16), respectively. Large tumour size is a prognostic indicator of poor outcome. CONCLUSION: Pure myoepithelial carcinoma of the breast adopts an aggressive clinical course with an outcome comparable to poorly differentiated adenocarcinoma of the breast.

The inframammary fold: contents, clinical significance and implications for immediate breast reconstruction.

The amount of breast tissue within the inframammary fold (IMF) is controversial. Preservation of the IMF during mastectomy facilitates breast reconstruction and led some surgeons to practice conservation of the IMF, contrary to traditional descriptions of total mastectomy. The aim of this study was to analyse the clinical significance of IMF tissue content. A total of 50 IMF specimens were studied from 42 patients who underwent mastectomy between January 2001 and December 2002. The amount of breast tissue within each IMF was evaluated. The median patient age was 46 (range 33-86) years. The median body mass index was 23.4 (18.1-38.3)kg/m(2). The median IMF volume resected was 2 (0.2-9.7)cm(3) which was 0.6 (0.1-2.0)% of the breast volume. Ten specimens (20%) contained breast tissue and one (2%) contained breast tissue and an inframammary lymph node. Three specimens (6%) containing fibrofatty tissue without breast parenchyma had intramammary lymph nodes within the IMF. One patient (2%) who had a mastectomy for invasive ductal carcinoma had IMF tissue containing a lymph node within the IMF with breast cancer metastasis. The presence of breast tissue or lymph nodes within the IMF was unrelated to patient age, body mass index, the amount of IMF tissue in relation to breast volume and absolute breast size. Our finding that breast tissue and intramammary lymph nodes are present in 28% of IMF specimens requires re-consideration of the safety of preserving the IMF at mastectomy. If IMF tissue is resected and the immediate breast reconstruction is performed, the superficial fascial system should be reconstructed after excision of the IMF tissue in order to recreate the inframammary crease.

Measurement of tumour size in case selection for breast cancer therapy by clinical assessment and ultrasound.

AIMS: Clinical assessment of tumour size is often used to choose between mastectomy and primary medical therapy. Clinical and imaging modalities may have varying levels of accuracy across the range of tumour sizes. The aim of this study was to compare the accuracy of clinical measurement and ultrasound in discriminating palpable tumours up to 3 cm vs those greater than 3 cm. METHODS: A prospective analysis of 111 consecutive patients with palpable breast cancer was performed. All women had clinical measurement by caliper and ultrasound assessment prior to any needle biopsy. Clinical measurement and ultrasound assessment of size were compared to pathological tumour size of the surgical specimen. RESULTS: Both clinical and ultrasound measurement underestimate the size of larger tumours. The overall accuracy of clinical assessment and ultrasound examination in correctly identifying a 30 mm cut off was 70.3 and 77.5%, respectively. Ultrasound was significantly more accurate at determining the size of tumours <30 mm (p=0.007) but there was no significant difference between both modalities in assessing tumours greater than 30 mm. CONCLUSIONS: Ultrasound assessment of breast cancer size is more accurate than clinical assessment for tumours less than 30 mm. As clinical examination is as accurate on ultrasound for tumours greater than 30 mm, clinical assessment of tumour size alone is adequate to select patients for primary medical therapy or mastectomy.

Squamous cell carcinoma of the breast: clinico-pathologic implications and outcome.

AIMS: Pure squamous cell carcinoma (SCC) of the breast is a rare tumour and little is known about long-term outcome. We report our experience of a consecutive series of patients. METHODS: All patients with SCC treated at our institution between 1970 and 2001 were included. The pathological features, outcome and prognosis were studied. RESULTS: Eleven patients were identified. The median age was 55 (38-90) years and median follow-up was 62 (3-332) months. Four tumours were T1, three were T2 and three were T3 (one tumour size was unknown). There were seven poorly differentiated and three moderately differentiated SCC. Tumour grade could not be assessed in one patient. Primary treatment was mastectomy in six patients, wide local excision in four patients and radiotherapy in one patient. There was lymph node (LN) involvement in two patients. Oestrogen receptor status was assessed in seven patients and only one tumour was positive. Adjuvant chemotherapy was given to three patients and five patients received adjuvant radiotherapy. Two patients developed local recurrence at 5 and 12 months and three patients developed distant metastasis at 2, 36 and 306 months. Three patients were treated with chemotherapy at recurrence. Three patients have died of the disease, two are alive with disease and six remain well. The 2- and 5-year overall survival was 80% (SE=13%) and 67% (SE=16%) respectively. Large tumour size and positive LN status were prognostic indicators of poor outcome. CONCLUSION: SCC of the breast adopts an aggressive course with outcome comparable to poorly differentiated breast adenocarcinoma.

A retrospective study comparing the individual modalities of triple assessment in the pre-operative diagnosis of invasive lobular breast carcinoma.

AIMS: Early invasive lobular breast carcinoma (ILC) is associated with few symptoms and signs. The individual sensitivity of clinical examination, mammography, ultrasonography, cytology and core biopsy have each been reported to be of limited value. The aim of this study was to evaluate the accuracy of triple assessment in the pre-operative detection of patients identified to have ILC from their surgical pathology. METHODS: Pure ILC was defined as tumours containing at least 90% lobular features. The triple assessment of 273 patients diagnosed primarily at our institution were reviewed. RESULTS: 87.5% of women were symptomatic and 12.5% were screen detected. The mean patient age was 59 (range 30-81) years and the median tumour size was 26 (range 5-110) mm. The main mammographic abnormalities were a spiculated lesion (33.3%), an ill-defined mass (33.3%) or architectural distortion (23.5%). The sensitivities for detecting ILC of each modality were: clinical examination (76.6%), mammography (79.8%), ultrasound examination (93.9%), fine-needle aspiration cytology (FNAC) (60.5%) and core biopsy (90.8%). Combining the three modalities of clinical examination, imaging and cyto/pathology increased the pre-operative detection rate of ILC. CONCLUSION: Triple assessment is useful in the diagnosis of ILC. As the features of ILC may be subtle, a high index of suspicion is required to facilitate early diagnosis.

Breast cancer in the inframammary fold: is preserving the inframammary fold during mastectomy justified?

INTRODUCTION: Preservation of the inframammary fold (IMF) during mastectomy facilitates breast reconstruction. The true incidence of breast cancer in the IMF is not well known. We report our experience of this condition. METHODS: The site and clinical features of initial presentation and recurrence of breast cancer within the breast in a consecutive series of 580 patients between 1997 and 2000 was studied. RESULTS: Primary breast tumours were detected within the IMF in four patients (0.7%). Only two tumours presenting within the IMF were visible on mammography. During the follow-up period, there were five patients with local recurrences involving either breast or skin flaps, but no breast cancer recurrence was observed in the IMF. CONCLUSION: Tumours within the IMF are rare but its occasional occurrence requires reconsideration of the safety of preserving the IMF at mastectomy.