The Evolving Role of Vacuum Assisted Biopsy of the Breast: A Progression from Fine-Needle Aspiration Biopsy.

BACKGROUND: The management of breast disease has been greatly facilitated by the technology of needle biopsy interventions, and over the past 30 years, this has evolved from the use of fine-needle aspiration biopsy (FNAB) to the current methodology of vacuum assisted biopsy (VAB). METHODS: This article provides an historical review of the application of needle interventions of the breast in the diagnosis and management of breast conditions, and discusses current indications for the use of vacuum assisted biopsies and vacuum assisted excisions. RESULTS: Whilst FNAB continues to have a limited role in breast disease diagnosis, the necessity of achieving an histological diagnosis has preferentially seen the development and wider application of automated core needle biopsies (CNB) and VAB in the assessment and management of breast lesions. The advantages of CNB and VAB include the ability to distinguish in situ and invasive disease pre-operatively, and the ability to achieve prior knowledge of immunohistochemical tumour markers particularly in the setting of neoadjuvant drug treatments. CONCLUSION: Due to its ability to obtain larger tissue samples, VAB does have diagnostic advantages over CNB and indications for the utilization of VAB are discussed. VAB additionally has an expanding role as a tool for breast lesion excision.

Columnar cell change with atypia (flat epithelial atypia) on breast core biopsy-outcomes following open excision.

Columnar cell change with atypia (CCCA) is a relatively recently recognized pathologic breast entity considered to be a risk factor for subsequent development of breast carcinoma. The aim of this study was to investigate the significance of finding CCCA on breast core biopsy, by establishing the frequency of other breast pathology on subsequently performed surgical excision specimens. All cases with CCCA as the most advanced lesion on core biopsy were reviewed. After excision, another advanced proliferative lesion was identified in 17 (33%) patients, including three patients (6%) with in situ or invasive carcinoma. An additional five patients (10%) were concurrently diagnosed with primary breast carcinoma at other sites. These findings indicate that when CCCA is found on core biopsy, open surgical biopsy of the relevant area should be performed and that workup of both breasts should be undertaken to exclude coexistent breast carcinoma at alternative sites.

High prevalence of human papillomaviruses in fresh frozen breast cancer samples.

While the etiology of breast cancer remains enigmatic, some recent reports have examined the role of human papillomavirus (HPV) in breast carcinogenesis. The purpose of this study was to determine the prevalence of HPV in breast cancer tissue using PCR analysis and sequencing. Fifty-four (54) fresh frozen breast cancers samples that were removed from a cohort of breast cancer patients were analyzed. Samples were tested for HPV using comprehensive PCR primers, and in situ hybridization was performed on paraffin embedded tissue sections. Findings were correlated with clinical and pathological characteristics. The HPV DNA prevalence in the breast cancer samples was 50% (27/54) with sequence analysis indicating all cases to be positive for HPV-18 type. While HPV patients were slightly younger, no correlation was noted for menopausal status or family history. HPV positive tumors were smaller with earlier T staging and demonstrated lesser nodal involvement compared to HPV negative cancers. In situ hybridization analyses proved negative. The high proportion of HPV positive breast cancers detected in this series using fresh frozen tissues cannot be dismissed, however the role of HPV in breast carcinogenesis remains unclear and may ultimately be ascertained by monitoring future breast cancer incidence amongst women vaccinated against high risk HPV types.

BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer.

We have recently demonstrated that BEX2 is differentially expressed in primary breast tumors and BEX2 expression is required for the Nerve Growth factor inhibition of ceramide-induced apoptosis in breast cancer. In this study we investigate the functional role of BEX2 in the survival and growth of breast cancer cells. We demonstrate that BEX2 downregulation induces mitochondrial apoptosis and sensitizes breast cancer cells to the pro-apoptotic effects of ceramide, doxorubicin and staurosporine. In addition, BEX2 overexpression protects the breast cancer cells against mitochondrial apoptosis. We show that this effect of BEX2 is mediated through the modulation of Bcl-2 protein family, which involves the positive regulation of anti-apoptotic member Bcl-2 and the negative regulation of pro-apoptotic members BAD, BAK1 and PUMA. Moreover, our data suggests that BEX2 expression is required for the normal cell cycle progression during G1 in breast cancer cells through the regulation of cyclin D1 and p21. To further support the significance of BEX2 in the pathogenesis of breast cancer we demonstrate that BEX2 overexpression is associated with a higher activation of the Bcl-2/NF-kappaB pathway in primary breast tumors. Furthermore, we show that BEX2 downregulation results in a higher expression and activity of protein phosphatase 2A. The modulation of protein phosphatase 2A, which is also known to mediate the cellular response to ceramide, provides a possible mechanism to explain the BEX2-mediated cellular effects. This study demonstrates that BEX2 has a significant role in the regulation of mitochondrial apoptosis and G1 cell cycle in breast cancer.

Structured ultrasonography workshop for breast surgeons: is it an effective training tool?

BACKGROUND: Effective training is essential to ensure satisfactory performance in surgeon-performed ultrasonography (US) and guided breast needle biopsies (USGBB). This study aimed to determine the efficacy of conducting a structured workshop in the teaching of breast US application and in guided biopsy techniques. METHODS: Consenting participants of the US for Surgeons Workshop at the General Surgeons Australia 2008 Annual Scientific Meeting were recruited. The workshop was divided into theoretical and practical components. For the theoretical component, brief pretests were administered, followed by lecture series, and then posttests. For the practical component, preinstructional USGBBs performed on breast phantoms and turkey breasts implanted with simulated lesions were assessed, followed by tutorials; it was concluded with postinstructional biopsy assessment. Points were deducted for simulated chest wall hits (complications). Previous experience and training in USBGG were recorded. Pre- and postlecture/instructional results were compared and the correlation tested using Student's t-test (p < 0.05). RESULTS: In all, 14 participants were recruited: 71% had no to moderate experience with USGBB. For the theoretical component, 33% improvement over the pretest (p < 0.001) was seen across all levels of experience. For the practical component, there was 56% improvement after instruction (p = 0.001), which was most marked in the moderate experience group (83%, p = 0.03). Two complications were recorded for the least experienced group prior to instructions, but no complications were seen following instructions. CONCLUSIONS: Structured workshops are effective for training surgeons in US application and USGBB and should be considered as part of standardized training guidelines and credentialing. Theory and practical components demonstrated similar efficacy and should be considered integral components in training programs. Formal training decreases complication rates, especially among the inexperienced.

Outcomes of multimodality breast screening for women at increased risk of familial breast cancer.

BACKGROUND: While population-based breast screening for women over the age of 50 years is a generally accepted and proven health strategy, the role of breast screening specifically among women at high risk of familial breast cancer has remained controversial. Indeed, there are very few services specifically offering a breast-screening program for women at high risk of familial breast cancer. METHODS: In 1999 a Familial Breast Cancer Screening Clinic (FBCSC) was established at the North Brisbane BreastScreen Queensland Service to provide a regular multimodality screening program utilizing clinical breast examination, breast ultrasound, and mammography for women at higher risk of hereditary breast cancer and with entry into the program commencing from the age of 30 years. RESULTS: Since its inception, a total of 2440 women have participated in the FBCSC. A total 7051 breast-screening examinations have been performed on these participants, with 53 breast cancers being diagnosed, including 8 in situ ductal carcinomas, 38 invasive ductal carcinomas, and 7 invasive lobular carcinomas. The mean size of the cancers was 16 mm (range = 1-45 mm), and of the 45 invasive cancers, 60% were less than or equal to 15 mm in size. The overall axillary node positive rate was 24.5% (13/53). The invasive cancer detection rate for first-round screening was 8.3 cancers per 1000 women screened, with 5.2 cancers per 1000 women detected on subsequent round screening. CONCLUSIONS: The results from this service demonstrate that multimodality screening for women at high risk of familial breast cancer and including women of younger age is effective and appropriate, with very acceptable cancer detection rates and pathological cancer characteristics being observed consistent with early-stage detection. The colocated siting of this service within a BreastScreen Queensland facility has proven to be efficient and cost effective.

No association between HPV positive breast cancer and expression of human papilloma viral transcripts.

Infectious agents are thought to be responsible for approximately 16% of cancers worldwide, however there are mixed reports in the literature as to the prevalence and potential pathogenicity of viruses in breast cancer. Furthermore, most studies to date have focused primarily on viral DNA rather than the expression of viral transcripts. We screened a large cohort of fresh frozen breast cancer and normal breast tissue specimens collected from patients in Australia for the presence of human papilloma virus (HPV) DNA, with an overall prevalence of HPV of 16% and 10% in malignant and non-malignant tissue respectively. Samples that were positive for HPV DNA by nested PCR were screened by RNA-sequencing for the presence of transcripts of viral origin, using three different bioinformatic pipelines. We did not find any evidence for HPV or other viral transcripts in HPV DNA positive samples. In addition, we also screened publicly available breast RNA-seq data sets for the presence of viral transcripts and did not find any evidence for the expression of viral transcripts (HPV or otherwise) in other data sets. This data suggests that transcription of viral genomes is unlikely to be a significant factor in breast cancer pathogenesis.

Hand-assisted laparoscopic adrenalectomy: an alternative minimal invasive surgical technique for the adrenal gland.

BACKGROUND: Presently the surgical approach to the adrenal gland is in a state of flux. While the traditional approach to the adrenal gland has been the open transabdominal technique, more recently laparoscopic approaches, particularly via the transabdominal route, have increasingly been utilized. However, laparoscopic intervention for the adrenal gland can be problematic in certain circumstances, particularly for large adrenal masses and in instances of adrenal malignancies. METHODS: In this report we describe the use of hand-assisted laparoscopic adrenalectomy as an alternative minimal invasive surgical approach to the adrenal gland. Hand-assisted laparoscopic adrenalectomy using the HandPort system (Smith & Nephew, Sydney, Australia) was undertaken in three patients requiring adrenalectomy for mass lesions including one patient with Conn's syndrome. RESULTS: In all three cases, surgery proceeded promptly and uneventfully. In the present paper, the details of the technique of hand-assisted adrenalectomy are described. This is the first report in the world literature of this new technique for the adrenal gland. CONCLUSIONS: Hand-assisted laparoscopic adrenalectomy is an easily performed technique, which can be completed within a short operative time span and which has the advantage of providing intraoperative tactile localization for the adrenal gland. It may be particularly applicable for large adrenal tumours, yet only involves the performance of a small abdominal incision. Postoperative recovery is comparable with that reported for the laparoscopic-only technique. Hand-assisted adrenalectomy is a new technique which has great potential and which warrants further evaluation.

Sentinel node biopsy for breast cancer: using local results for estimation of risk to the patient.

BACKGROUND: Sentinel node biopsy (SNB) is being increasingly used but its place outside randomized trials has not yet been established. METHODS: The first 114 sentinel node (SN) biopsies performed for breast cancer at the Princess Alexandra Hospital from March 1999 to June 2001 are presented. In 111 cases axillary dissection was also performed, allowing the accuracy of the technique to be assessed. A standard combination of preoperative lymphoscintigraphy, intraoperative gamma probe and injection of blue dye was used in most cases. Results are discussed in relation to the risk and potential consequences of understaging. RESULTS: Where both probe and dye were used, the SN was identified in 90% of patients. A significant number of patients were treated in two stages and the technique was no less effective in patients who had SNB performed at a second operation after the primary tumour had already been removed. The interval from radioisotope injection to operation was very wide (between 2 and 22 h) and did not affect the outcome. Nodal metastases were present in 42 patients in whom an SN was found, and in 40 of these the SN was positive, giving a false negative rate of 4.8% (2/42), with the overall percentage of patients understaged being 2%. For this particular group as a whole, the increased risk of death due to systemic therapy being withheld as a consequence of understaging (if SNB alone had been employed) is estimated at less than 1/500. The risk for individuals will vary depending on other features of the particular primary tumour. CONCLUSION: For patients who elect to have the axilla staged using SNB alone, the risk and consequences of understaging need to be discussed. These risks can be estimated by allowing for the specific surgeon's false negative rate for the technique, and considering the likelihood of nodal metastases for a given tumour. There appears to be no disadvantage with performing SNB at a second operation after the primary tumour has already been removed. Clearly, for a large number of patients, SNB alone will be safe, but ideally participation in randomized trials should continue to be encouraged.

Exploring the prevalence of ten polyomaviruses and two herpes viruses in breast cancer.

Several different viruses have been proposed to play a role in breast carcinogenesis. The aim of this study was to investigate the prevalence of a subset of viruses in breast cancer tissue. We investigated the prevalence of 12 DNA viruses: EBV and CMV from the Herpesviridae family and SV40, BKV, JCV, MCV, WUV, KIV, LPV, HPyV6, HPyV7, and TSV from the Polyomaviridae family in 54 fresh frozen breast tumour specimens. Relevant clinical data and basic lifestyle data were available for all patients. The tissue samples were DNA extracted and real-time PCR assays were used for viral detection.The highest prevalence, 10% (5/54), was found for EBV. MCV, HPyV6, and HPyV7 were detected in single patient samples (2% each), while WUV, KIV, JCV, BKV, LPV, SV40, TSV and CMV were not detected in the 54 breast cancer specimens analysed here. Further investigations are needed to elucidate the potential role of viruses, and particularly EBV, in breast carcinogenesis.

The role of ultrasound in the management of breast disease.

Surgeon-performed ultrasound has also been increasingly utilised by breast surgeons in particular, who find ultrasound an invaluable tool in the office to assist in the management of breast patients, and also in the operating room where it can be used to directly guide excision of impalpable breast lesions without the use of hookwires2,3. In the future, the role of ultrasound will continue to grow, particularly with the advent of 3-D ultrasound, and in the evolving area of breast lesion ablation techniques using modalities such as radiofrequency ablation or laser therapy. Ultrasound is a very important tool in the assessment and management of breast disease and it has dramatically changed the way breast cancer patients are managed.