Vacuum assisted stereotactic guided mammotome biopsies in the management of screen detected microcalcifications: experience of a large breast screening centre.

AIM: To evaluate the usefulness of vacuum assisted stereotactic guided mammotome biopsy in the diagnostic management of screen detected calcifications and to rationalise its use versus diagnostic excision. METHODS: The first 100 mammotome biopsies preceded by a conventional needle core biopsy (NCB) were identified from the database of Leeds/Wakefield Breast Screening Service. The histological diagnosis on NCB and mammotome were reviewed and compared with the surgical histological diagnosis if excision had been performed. RESULTS: Using mammotome, diagnoses were changed in 74 of the 100 cases. In 66 cases a definitive diagnosis (B2 or B5) was obtained. The incidence of inadequate/unsatisfactory (B1) biopsies was reduced from 36% to 9%. In 34 cases mammotome was not helpful in arriving at a definite diagnosis (B1/B3/B4). All cases diagnosed as malignant with mammotome were proven to have in situ or invasive malignancy on excision except for one case of ductal carcinoma in situ fully excised by mammotome. There was one false negative case of in-situ carcinoma with a prior benign (B2) mammotome diagnosis. Almost half the NCB uncertain (B3) cases required excision as the mammotome biopsies were also uncertain (B3). The majority were flat epithelial atypia and atypical intraductal proliferation. CONCLUSIONS: Mammotome biopsy is particularly useful for further assessment of an inadequate (B1) or suspicious (B4) NCB diagnosis. Diagnostic surgical excision remains the method of choice for managing atypical/uncertain lesions (B3).

Needle core biopsy can reliably distinguish between benign and malignant papillary lesions of the breast.

AIMS: To review 21 screen-detected papillary lesions in which the core biopsy findings suggested a papillary lesion and to correlate pathological and radiological findings in order to assess the risks of associated malignancy and the need for surgical intervention. The appropriate management of non-malignant papillary breast lesions detected on needle core biopsy (NCB) is currently uncertain. METHODS AND RESULTS: Forty-seven papillary breast lesions with a histological diagnosis of papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), multiple papillomas, 'papillomatosis' or papillary carcinoma (invasive or in situ) were identified from records at the Leeds Breast Screening and Assessment Unit. The cases were diagnosed between between May 1995 and May 2002. In 21 cases the previous NCB contained a papillary proliferation which had been categorized as either 'B2', benign, 'B3', of uncertain malignant potential, or 'B4', suspicious of malignancy. All of the 19 'B3' or 'B4' cases and one of the two 'B2' lesions had undergone open surgical biopsy. All cases with a previous 'B4' were malignant on subsequent excision. All excised cases with a previous 'B3' or 'B2' were found benign, although four of the 'B3's derived from papillomata associated with an atypical proliferation amounting to ADH. In three of these four (75%) the papillary proliferation had been associated with epithelial hyperplasia of usual type (HUT) on the core and the radiological features were of a mass lesion detected on incident round screen which had increased in size. CONCLUSION: Our results confirm the accuracy of NCB in the diagnosis of screen-detected papillary lesions of the breast. Surgical excision may not always be necessary following a 'B3' core biopsy.

Surgical excision is warranted following a core biopsy diagnosis of mucocoele-like lesion of the breast.

AIMS: Mucocoele-like lesions (MLLs) of the breast are unusual lesions in which mucin-filled ducts or cysts are accompanied by extrusion of mucin into surrounding stroma. A possible diagnosis of MLL may be suggested by the finding of mucin-filled ducts or cysts and/or stromal mucin in a core biopsy sample. Whether such findings should prompt immediate open diagnostic biopsy to exclude malignancy is currently uncertain, although this represents current practice in our institution. In this study we have reviewed 11 cases of possible MLL on core biopsy correlating both pathological and radiological findings in order to determine the risks of associated malignancy and whether excision is the most appropriate management option. METHODS AND RESULTS: Eleven cases of possible MLL presenting via the Breast Screening and Assessment Unit in Leeds since April 1999 were identified by review of pathological records. Histological slides, mammograms and ultrasound images were reviewed. Ten of the 11 had undergone open surgical biopsy for diagnosis. Three of the 10 (30%) proved to derive from malignant lesions. Two were ductal carcinoma in situ (DCIS) and one was an invasive mucinous carcinoma. All three cases had an associated atypical epithelial proliferation which, in a surgical excision, would be classified as atypical ductal hyperplasia (ADH) at least, as well as mucin in the core biopsy sample. The majority of possible MLLs presented radiologically as coarse calcification, but two of four (50%) which had a radiological mass subsequently proved malignant. Seven cases were without atypia on the core and all subsequently proved benign. Three of these, however, were associated with ADH on the excision biopsy. CONCLUSION: Surgical excision is warranted following a core biopsy suggestion of possible MLL when mucin-filled ducts or cysts and stromal mucin have been seen. The risk of malignancy is high when the core biopsy also contains an atypical epithelial proliferation (100% in our series) and also when there is an associated radiological mass lesion. In cases without atypia on the core a significant proportion of cases (43%) are associated with ADH on excision.

Can the NHS Breast Screening Programme afford not to double read screening mammograms?

AIM: Rapid expansion of the National Health Service (UK) Breast Screening Programme (NHSBSP) to routinely invite women aged 50-70 years will result in many new readers undertaking screen reading. A timely method for assessing performance and preferably one that facilitates a steep learning curve will be required. MATERIALS AND METHODS: This unit screens a population of 88000 women aged 50-64 years and double reads >90% films. A record is kept of proven screen-detected cancers not recalled for assessment by either the first or second reader but correctly recalled following third-reader arbitration. Individual readers' workload and recall rates are obtained by running an annual co-writer report. The results of this 7 year prospective audit are presented. RESULTS: In total 177167 women were screened between 1/4/95 and 31/3/02 resulting in the detection of 1072 cancers. Eighty-seven cancers (8.1%) were detected after arbitration. Individual readers recall to assessment rates and percentage of cases incorrectly returned to routine recall varied. Prompt feedback of missed/misinterpreted cases allowed both experienced and inexperienced readers to modify their recall thresholds for particular mammographic abnormalities. CONCLUSION: It is recommended this audit method is adopted by all units in the NHSBSP and that the Advisory Committee for Breast Cancer Screening review the policy of single versus double reading.

Will the spectrum of lesions prompting a "B3" breast core biopsy increase the benign biopsy rate?

AIM: To audit the benign surgical biopsies in women screened, assessed, and referred by the Leeds/Wakefield Breast Screening Unit for the year 1999-2000 with a view to determining any association with a preoperative B3 core biopsy categorisation. METHODS: The results of all preoperative diagnostic procedures in all patients who underwent surgical excision for a lesion proving benign in the year 1999-2000 were reviewed. Cases were categorised according to whether the preoperative fine needle aspirate cytology (FNAC) or core biopsy had been equivocal or of uncertain malignant potential (C3/B3), inadequate or unrepresentative (C1/B1), or benign (C2/B2). In those cases with a C3/B3 FNAC or core biopsy result, reasons for the uncertainty were determined by examination of the report and, where necessary, slides. In cases with C1/B1 or C2/B2 investigations and in those without a preoperative procedure, the reasons for surgical referral were determined from the screening records. Case records of all patients with a B3 core biopsy categorisation who subsequently proved to have malignancy were also reviewed. RESULTS: Thirty six women had benign surgical biopsies in the 1999-2000 screening year. In 13 of the 36 patients, referral for diagnostic biopsy rested on radiological and/or pathological suspicion of radial scar. The core biopsy category was B3 in all but one, which was in the B1 category. In a further 10 patients, referral was based primarily on a pathological B3 categorisation. The reasons for this were as follows: papillary lesion (two), fibroepithelial lesion (two), atypical intraductal epithelial proliferation (two), stromal mucin (two), atypical lobular hyperplasia (one), and an unusual vascular lesion (one). Two cases with a C3 on FNAC also derived from papillary lesions. In the remaining nine patients, the radiological features were sufficiently suspicious to prompt referral in the presence of either inadequate/unrepresentative (C1/B1) or benign (B2) preoperative pathological findings. Two women had no preoperative needle biopsy. CONCLUSIONS: In 22 of 36 benign biopsies, the initial core biopsy categorisation was B3. According to the current system of core biopsy categorisation, a diversity of lesions must be designated as of "uncertain malignant potential" (B3) because the technique provides insufficient tissue for full histological assessment. The use of this category may increase the number of benign biopsies if all such cases are referred for surgery. An increase in the benign biopsy rate may be averted if larger amounts of tissue can be obtained using newer vacuum assisted techniques such as the Mammotome.

Routine breast screening for women aged 65-69: results from evaluation of the demonstration sites.

Routine programme data and specially designed surveys from 3 demonstration sites were analysed to determine the implications of extending the NHS Breast Screening Programme (NHSBSP), to include routine invitations for women up to 69 years. All women aged 65-69 and registered with GPs in these areas received routine invitations for breast screening along with those aged 50-64. Overall uptake was 71% in women aged 65-69 compared with 78% in younger women, but was > or = 90% in both groups who had previously attended within 5 years. Recall rates were lower for older women, but with a higher positive predictive value for cancer. The percentages of invasive cancer in different prognostic categories were similar in the 2 age groups. Older women took no longer to screen than younger women. The costs per woman invited or per woman screened were also similar to those for women aged 50-64, whilst the cost per cancer detected was some 34% lower in older women. Breast screening is as cost effective for women aged 65-69 as for those aged 50-64, with a higher cancer detection rate balancing shorter life expectancy. The proposed extension to the national programme will have considerable workforce implications for the NHSBSP and require additional resources.

A novel approach for studying endogenous abeta processing using cultured primary neurons isolated from APP transgenic mice.

The central component of senile amyloid plaques in Alzheimer's disease (AD) is the beta-amyloid peptide (Abeta), derived from proteolytic processing of the amyloid precursor protein (APP). In this study, we developed an in vitro model to measure and identify soluble Abeta from primary cortical neurons. Neurons were isolated from mice transgenic for human APP695 containing the K670N, M671L double mutation. We characterized soluble Abeta using Western blot and ELISA assays. We found that the Abeta levels in conditioned media from these neurons were readily detectable and almost five times higher than in CSF. The majority of Abeta in the media was Abeta1-40; however, Abeta1-42 was also detectable. When the neurons were exposed to Phorbol 12-myristate 13-acetate (PMA), alpha1-antichymotrypsin, or alpha1-antitrypsin, the alterations of soluble Abeta levels were consistent with other models reported. Most importantly, the soluble Abeta in our model was remarkably stable, and aliquots were unchanged after prolonged incubations or repeated freeze/thaw cycles. The Abeta appeared to be monomeric by Western blot analysis. Soluble Abeta coimmunoprecipitated with endogenous mouse apolipoprotein E from the primary cultures. Taken together, our data demonstrated that using a Western blot assay to detect soluble Abeta from transgenic mouse overexpressing APP695 is sensitive, specific, and reliable and provides an accessible model for examining the neuronal metabolism of APP and Abeta.

Pre-operative estimation of primary breast cancer size: a comparison of clinical assessment, mammography and ultrasound.

This prospective study aimed to determine which is the most precise modality for the pre-operative measurement of primary breast cancers: clinical palpation; mammography; or ultrasound. Analysis of the difference between the measurement of the maximum tumour diameter by these three modalities and by the histological measurement was performed in 210 cases. Clinical palpation tended to overestimate tumour size and gave the largest standard deviation of the difference. Ultrasound and mammography both gave a similar standard deviation of the difference, with ultrasound tending to underestimate tumour size. For all modalities, the standard deviation and the 95% confidence intervals of the difference increased with increasing tumour size. There is little difference between the precision of ultrasound and mammography in measuring tumour size. The wide 95% confidence intervals for any method of pre-operative tumour measurement should be considered when planning patient management.

New mammographic stromal deformity: what is the significance of this finding on screening mammograms?

Current practice within the NHS Breast Screening Programme recommends surgical excision of screen detected areas of stromal deformity as differentiating carcinomas from radial scars and excluding in situ malignancy in association with radial scars is unreliable. We retrospectively reviewed all cases recalled for assessment over a 4 year period, identified to have an area of persistent stromal deformity not associated with surgical scarring and without an associated mammographic mass. Thirty women were prevalent (first) round screens--17 cases proved to be malignant and 13 benign. The latter group included three cases of atypical ductal hyperplasia. Nineteen women were incident (subsequent) round screens--all 19 cases proved to be malignant. This study supports the practice of surgically removing all areas of stromal deformity, particularly new areas of stromal deformity detected in the incident round, as in this group the likelihood of malignancy is extremely high.

Are too many breast cancers missed at assessment?

Interval breast cancers presenting between screening episodes are an inevitable occurrence but their number should to be kept to a minimum. The objectives of this study were to ascertain the proportion of interval cancers developing in women who had been recalled for assessment after their initial screen and to review the assessment process. Interval cancers presenting after false negative assessment accounted for a small proportion (6%) but some cancers may have been diagnosed earlier if image guided FNAC or core biopsy had been included in the assessment process.

Breastfeeding and the use of recreational drugs--alcohol, caffeine, nicotine and marijuana.

This paper both reviews the current literature and explores anecdotal information as reported by Nursing Mothers' Breastfeeding Counsellors relating to breastfeeding and the use of alcohol, caffeine, nicotine and marijuana. All of these drugs do enter breastmilk to some extent and can have a detrimental effect on the production, volume, composition and ejection of breastmilk, as well as a direct adverse effect on the infant. Breastfeeding mothers should be encouraged to restrict their intake of these so-called recreational drugs. It is acknowledged that this is a particularly stressful period in a mother's life and that she may need additional support and practical suggestions to limit the exposure of these drugs to the infant.

Human lung carcinomas express Fas ligand.

To reach a clinically detectable size, neoplasms must be able to suppress or evade a host immune response. Activated T cells may enter apoptosis in the presence of Fas ligand (FasL) (1), and tissue expression of FasL has been shown to contribute to immune privilege in the eye and testis (2, 3). We have demonstrated that all human lung carcinoma cell lines tested (16 of 16) express a Mr 38,000 protein consistent with FasL by immunoblotting, whereas the majority of resected tumors (23 of 28) show positive staining for FasL by immunohistochemistry. DNA sequencing of reverse transcription-PCR products from lung cancer cells and resected lung tumors confirms the presence of human FasL mRNA in these neoplastic tissues. Furthermore, lung carcinoma cells are capable of killing a Fas-sensitive human T cell line (Jurkat) in coculture experiments; this killing was inhibited by a recombinant form of the soluble portion of the Fas receptor (FasFc). FasL expression by neoplastic cells represents a potential mechanism for peripheral deletion of tumor-reactive T-cell clones.

The role of ultrasound imaging in the diagnosis of breast implant rupture: a prospective study.

Breast ultrasound to assess possible implant rupture was performed on 24 consecutive patients (43 breasts) by the same radiologist immediately before revisional breast implant surgery. Comparison of the clinical, ultrasound and operative findings showed ultrasound to be three times as sensitive as clinical judgement in predicting implant rupture. The sensitivity of ultrasound in predicting impaired implant integrity was 70% (versus 23% for clinical examination) with a specificity of 96%. The ultrasound features indicating leakage are outlined later. The positive predictive value of an abnormal scan was 90% and that of a normal scan 87%. It is concluded that breast ultrasound is a simple, quick, non-invasive method which contributes significantly to the assessment of patients with suspected breast implant rupture.

Occurrence of Shiga-like toxin-producing Escherichia coli in retail fresh seafood, beef, lamb, pork, and poultry from grocery stores in Seattle, Washington.

Fresh meat, poultry, and seafood purchased from Seattle area grocery stores were investigated for the presence of Shiga-like toxin-producing Escherichia coli by using DNA probes for Shiga-like toxin (SLT) genes I and II. Of the 294 food samples tested, 17% had colonies with sequence homology to SLT I and/or SLT II genes.

Silicone breast implant rupture: common/serious complication?

Of the potential health risks of silicone breast implants it is the concern about implant durability, life span and the possible association with connective tissue disease which has attracted most attention. A prospective study addressing these factors was therefore undertaken over an 11 month period. 51 patients presenting with significant capsular contracture, suspected prosthesis rupture or unrelieved implant-induced anxiety underwent revisional breast surgery after biochemical, haematological and immunological screening. Of these 51 patients (83 breasts), 14 (19 breasts) had ruptured implants (23% incidence). These were all smooth prostheses belonging to a cohort manufactured more than 10 years ago; their mean in situ duration being 12 years vs. 5.5 years for the intact group (p = 0.0024; Kruskal-Wallis one-way ANOVA). There were no systemic complications from implant rupture and the mean blood silicon level was normal. One patient with pre-existing pernicious anaemia had elevated autoantibodies. The mean ESR in the ruptured implant group was 6 mm/hour. It is concluded that rupture of breast implants is not as uncommon as hitherto thought and is strongly correlated with their in situ duration. In this study implant gel leakage was not associated with serious systemic effects.

Assessment of the role of ultrasound in the differentiation of radial scars and stellate carcinomas of the breast.

Radial scars are benign lesions of the breast which cannot be reliably distinguished from carcinoma by their mammographic appearances alone [1,2]. The present wisdom is that all such lesions should be biopsied [2]. We report a retrospective study carried out to assess whether there are any ultrasound imaging features that may be useful in differentiating radial scars from carcinoma and so reduce the need for excision biopsy. Over a period of 44 months between 1988 and 1992, 530 patients underwent surgery for abnormalities detected by routine mammographic screening. Of the 191 benign lesions excised, 24 were radial scars. Ultrasound images of 21 radial scars were mixed with an equal number of images of histologically proven carcinomas that had similar mammographic appearances. These images were reviewed 'blind' by a single radiologist. We were unable to find any ultrasound appearances sufficiently specific to radial scars to allow confident exclusion of malignancy. We therefore endorse the current practice of biopsying all mammographically detected stellate lesions.