The impact of vacuum-assisted excision in the management of indeterminate B3 lesions in the NHS Breast Screening Programme in England.

AIM: To assess the impact of vacuum-assisted excision (VAE) on the management of B3 lesions in the England NHS Breast Screening Programme following an update of national guidance. A secondary aim was to investigate the histological features of malignancies resulting from upgrade of B3 lesions by either VAE or surgery. MATERIALS AND METHODS: The study population was all women recalled for assessment after breast screening who had a wide-bore needle biopsy with a B3 result over the period 01/04/2018 to 31/03/2019. Data were extracted from the National Breast Screening Service (NBSS) computer system at unit level. Women with a B3 result were split into those with and without atypia. The upgrade rates and histological features of malignancies in the different groups were analysed. RESULTS: In total, 2,234,514 women attended for screening between 1/4/218 and 31/3/2019, 84,559 women were referred to assessment, and of those 40,037 women had a core biopsy resulting in 3,355 were B3 lesions (8.38%). Within these, 556 cancers were diagnosed, giving an upgrade rate of 16.57% (556/3,355). The upgrade for B3 lesions with atypia was significantly higher than for B3 lesions without atypia (29.1% versus 13.3%, p<0.001). CONCLUSION: The introduction of the new B3 guidelines has resulted in 73.8% of B3 lesions with atypia and 65.1% of B3 lesions with no atypia having VAE rather than surgery. The data highlights the importance of managing these indeterminate lesions appropriately with an overall upgrade rate of 16.57%.

Contrast-enhanced spectral mammography improves diagnostic accuracy in the symptomatic setting.

AIM: To assess the diagnostic accuracy of contrast-enhanced spectral mammography (CESM), and gauge its "added value" in the symptomatic setting. MATERIALS AND METHODS: A retrospective multi-reader review of 100 consecutive CESM examinations was performed. Anonymised low-energy (LE) images were reviewed and given a score for malignancy. At least 3 weeks later, the entire examination (LE and recombined images) was reviewed. Histopathology data were obtained for all cases. Differences in performance were assessed using receiver operator characteristic (ROC) analysis. Sensitivity, specificity, and lesion size (versus MRI or histopathology) differences were calculated. RESULTS: Seventy-three percent of cases were malignant at final histology, 27% were benign following standard triple assessment. ROC analysis showed improved overall performance of CESM over LE alone, with area under the curve of 0.93 versus 0.83 (p<0.025). CESM showed increased sensitivity (95% versus 84%, p<0.025) and specificity (81% versus 63%, p<0.025) compared to LE alone, with all five readers showing improved accuracy. Tumour size estimation at CESM was significantly more accurate than LE alone, the latter tending to undersize lesions. In 75% of cases, CESM was deemed a useful or significant aid to diagnosis. CONCLUSION: CESM provides immediately available, clinically useful information in the symptomatic clinic in patients with suspicious palpable abnormalities. Radiologist sensitivity, specificity, and size accuracy for breast cancer detection and staging are all improved using CESM as the primary mammographic investigation.

Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response.

BACKGROUND: Checkpoint kinase1 (CHK1), which is a key component of DNA-damage-activated checkpoint signalling response, may have a role in breast cancer (BC) pathogenesis and influence response to chemotherapy. This study investigated the clinicopathological significance of phosphorylated CHK1 (pCHK1) protein in BC. METHOD: pCHK1 protein expression was assessed using immunohistochemistry in a large, well-characterized annotated series of early-stage primary operable invasive BC prepared as tissue microarray (n=1200). RESULT: pCHK1 showed nuclear and/or cytoplasmic expression. Tumours with nuclear expression showed positive associations with favourable prognostic features such as lower grade, lower mitotic activity, expression of hormone receptor and lack of expression of KI67 and PI3K (P<0.001). On the other hand, cytoplasmic expression was associated with features of poor prognosis such as higher grade, triple-negative phenotype and expression of KI67, p53, AKT and PI3K. pCHK1 expression showed an association with DNA damage response (ATM, RAD51, BRCA1, KU70/KU80, DNA-PKCα and BARD1) and sumoylation (UBC9 and PIASγ) biomarkers. Subcellular localisation of pCHK1 was associated with the expression of the nuclear transport protein KPNA2. Positive nuclear expression predicted better survival outcome in patients who did not receive chemotherapy in the whole series and in ER-positive tumours. In ER-negative and triple-negative subgroups, nuclear pCHK1 predicted shorter survival in patients who received cyclophosphamide, methotrexate and 5-florouracil chemotherapy. CONCLUSIONS: Our data suggest that pCHK1 may have prognostic and predictive significance in BC. Subcellular localisation of pCHK1 protein is related to its function.

Qualitative mammographic findings and outcomes of surveillance mammography after partial breast reconstruction with an autologous flap.

BACKGROUND: This study describes the qualitative mammographic features after partial breast reconstruction with an autologous flap, and evaluates the diagnostic accuracy and recall rates of surveillance mammography after volume replacement in breast conserving surgery. METHODS: Patients who had autologous partial breast reconstruction (N = 102) after breast-conserving surgery using either the myocutaneous latissimus dorsi mini-flap (N = 39) or fasciocutaneous chest wall perforator flap (N = 63) were reviewed. Mammograms done at one-year post surgery were analysed for characteristic qualitative features. All surveillance mammograms, diagnostic imaging and medical records were retrospectively reviewed. RESULTS: Mammograms of partially reconstructed breasts had distinctive features that correlated well with the surgical procedures. Median follow-up was 3 years, range 0-11 years. Of 295 surveillance mammograms, six (2%) resulted in a recall for further imaging and 3 (1%) proceeded to needle biopsy. Diagnostic imaging was performed for 13 (13/102, 12.7%) patients with symptoms, and only one (1/102, 1%) required a diagnostic biopsy. CONCLUSIONS: A conserved breast with an autologous flap within has characteristic mammographic features that differ from those after standard breast conserving surgery. Surveillance mammography after partial breast reconstruction is accurate, and recall/biopsy rates are low. Diagnostic breast ultrasound examination is effective evaluation for the symptomatic patient.

CT staging for breast cancer patients with poor prognostic tumours.

The aim of this study was to assess the value of computed tomography (CT) staging of the chest, abdomen and pelvis in patients with poor prognostic tumours and no symptoms of metastatic disease in those who have undergone primary surgical management for the treatment of breast cancer. Patients who had primary operable invasive breast cancer treated by surgery over a 2-year period were retrospectively identified. Pathological data from the surgical resection were used to calculate the Nottingham Prognostic Index. Patients with no symptoms of distant metastases who underwent CT staging of the chest, abdomen and pelvis as a result of being placed in the poor prognostic group were identified. The presence and sites of metastatic disease or any indeterminate finding were documented. Additional investigations generated as a result of the staging CT and the outcome were also recorded. Sixty-seven patients (80%) in the poor prognostic group underwent a staging CT. Forty-seven patients (70%) had no signs of metastatic disease on the staging CT. Two patients (3%) were diagnosed with metastatic disease, on the basis of the initial CT scan. Eighteen patients (27%) had an indeterminate finding requiring further investigation, generating 21 additional imaging tests - following this only one additional patient was diagnosed with metastatic disease. Seventeen patients with an initially indeterminate finding did not have metastatic disease, giving a false-positive rate of 25%. In total, three patients (4%) had a final diagnosis of metastatic disease. The routine use of CT staging in patients with no symptoms of distant metastases with primary operable breast cancer even when in a poor prognostic group is of limited value, with a low pick-up rate of metastatic disease and considerable risk of false-positive findings.

Does the insertion of a gel-based marker at stereotactic breast biopsy allow subsequent wire localizations to be carried out under ultrasound guidance?

AIM: To investigate whether the insertion of a gel-based marker at the time of stereotactic breast biopsy allows subsequent preoperative localization to be performed under ultrasound guidance. MATERIALS AND METHODS: One hundred consecutive women who underwent either a 10 G stereotactic vacuum-assisted breast biopsy or 14 G stereotactic core biopsy with marker placement, followed by wire localization and surgical excision were identified. All had mammographic abnormalities not initially visible with ultrasound. The method of preoperative localization was recorded and its success judged with reference to the wire position on the post-procedure films relative to the mammographic abnormality and the marker. Histopathology data were reviewed to ensure the lesion had been adequately excised. RESULTS: Eighty-three women (83%) had a successful ultrasound-guided wire localization. Successful ultrasound-guided localization was more likely after stereotactic vacuum biopsy (86%) compared to stereotactic core biopsy (68%), although this did not quite reach statistical significance (p=0.06). CONCLUSION: The routine placement of a gel-based marker after stereotactic breast biopsy facilitates preoperative ultrasound-guided localization.

The prognostic significance of computerised tomography findings in women with liver metastases from breast cancer.

AIMS: While computerised tomography (CT) is used for diagnosis and assessing response to treatment little work has been performed on the prognostic significance of the CT findings in women with liver metastases. The aim of this study was to assess if the CT findings in women diagnosed with liver metastases at the time of first presentation with metastatic breast cancer have any prognostic significance. MATERIALS AND METHODS: The staging CT scans of 78 consecutive women diagnosed with liver metastases at the time of first presentation of metastatic breast cancer were reviewed independently by two radiologists who were blinded to survival and the histological features of the tumour. The number and enhancement characteristics of liver metastases, whether metastases were solitary, multiple or diffuse, the diameter of the largest and the sum of the diameter of the five largest lesions, an estimate of % involvement (<10%, 10-50%, >50%), and the presence of metastases at other sites were assessed. HER-2 and ER status and histological grade of the patient's primary breast cancer were also recorded. Survival was ascertained from hospital records. The prognostic significance of these factors was assessed in a univariate and multivariate fashion. RESULTS: At univariate analysis, number of liver metastases, sum of the diameter of the five largest lesions, percentage estimated involvement, presence of ascites, chest metastases and HER-2 status were significantly associated with reduced survival. Liver metastasis pattern (i.e. whether discrete or multiple), enhancement characteristics, ER status and histological grade were not associated with a significant outcome. At multivariate analysis estimated percentage liver involvement and the presence of chest metastases retained prognostic significance. Estimated percentage involvement was reproducible with 90% concordance between the two observers. CONCLUSIONS: The CT appearances of patients with liver metastases at first presentation with metastatic breast cancer provide prognostic information which may be clinically useful.

Frequency and patterns of metastatic disease in locally advanced inflammatory and non-inflammatory breast cancer.

AIMS: To determine the frequency and pattern of metastatic disease as detected by staging computed tomography in patients presenting with locally advanced primary breast cancer, comparing non-inflammatory and inflammatory subtypes. MATERIALS AND METHODS: Patients who underwent staging computed tomography for locally advanced breast cancer were identified from the hospital's computerised radiology system. The computed tomography scans, breast imaging and pathology were reviewed. RESULTS: Over a 29 month period, 97 patients underwent staging computed tomography for locally advanced primary breast cancer. Sixteen patients (16%) were found to have metastatic disease at presentation. Thirty-eight patients (39%) presented with the inflammatory subtype and 59 patients (61%) with the non-inflammatory subtype. Metastases were significantly more likely in patients with the inflammatory subtype, with 10 patients (26%) having metastases at presentation compared with six patients (10%) with the non-inflammatory subtype (P=0.034). Metastases to the lung and the pleura were the most commonly encountered sites, with pleural-based metastases more likely in patients with the inflammatory subtype (P=0.05). CONCLUSION: Routine computed tomography staging of patients with locally advanced breast cancer is worthwhile with the inflammatory subtype of locally advanced disease having the higher risk of metastatic disease at presentation. Pleural-based metastatic disease is more likely in patients with the inflammatory subtype.

A survey of current UK practice regarding the biopsy of clinically and radiologically benign breast masses in young women.

AIM: To determine current practice in the UK of needle sampling of clinically and radiologically benign breast masses in young women. METHOD: A questionnaire regarding needle sampling practice in young women with clinically and radiologically benign breast masses was sent to 481 members of the Royal College of Radiologists Breast Group. This included questions on whether a written protocol is in place to allow avoidance of biopsy, and if so, the clinical and radiological criteria used. RESULTS: Responses were available for analysis from 80 units. Forty-two (53%) units had no written policy in place, whilst 38 (47%) adhered to a written policy. Of those with a policy, an age criterion for safe avoidance of biopsy was present in 36 out of the 38 units (95%). The age limit used ranged from <25 years to <35 years. Twenty-seven (71%) written policies included clinical criteria but only four (10%) policies included a size criterion. Radiological criteria were present in all policies and the majority (74%) adhered to full Stavros criteria. Seven units (18%) used a revised form of the Stavros criteria and three units used their own criteria. CONCLUSION: There is little concordance between symptomatic breast clinics regarding the criteria for avoidance of breast biopsy in this young patient group. Given the very low incidence of breast carcinoma in women less than 25 years old it is considered safe and feasible to adopt a standardized protocol across the UK and avoid the often-unnecessary benign biopsies in these patients.

Optimal screening mammography reading volumes; evidence from real life in the East Midlands region of the NHS Breast Screening Programme.

AIM: To assess real-life reader performance as a function of both volume of mammograms read and reading experience in a multicentre cohort. MATERIALS AND METHODS: Thirty-seven film readers from the East Midlands Breast Screening Programme had 3 years of consecutive screen reading results available for comparison. Markers of screening performance as the first film reader [cancer detection rates, small cancer detection rates, recall rates, positive predictive value of recall (PPV), and missed cancers] were compared with both volume of films read and years of film reading experience. For reading volume, readers were categorized according to film reading volume over the 3 year period: < 15,000 (i.e., on average less than the recommended 5000/year); 15-< 20,000; 20-< 25,000; and ≥ 25,000. For years of experience, readers were categorized into the following groups: < 5 years, 5-< 10 years, 10-< 15 years, and 15-< 20 years. RESULTS: There was no evidence to suggest a relationship between years of film reading experience and film-reading performance. For reading volume, there was a significant difference in the distribution of cancer-detection rate between the four groups (p=0.01); however, there was no difference in small cancer-detection rates, missed cancers or PPV. The median cancer detection rate in the high-volume group (≥ 25,000 mammograms/3 years) was significantly lower than the other groups combined (6.9 per 1000 women screened versus 7.9 per 1000 women screened). The lowest median recall rate was also in the high-volume group, whilst those readers not meeting the NHSBSP minimum requirement had the highest median recall rate; however, there was borderline evidence to suggest a difference in the distribution of recall rates between the four groups. CONCLUSION: The data from the East Midlands do not provide any evidence for reducing the threshold volume of 5000 cases /year. However, there appears to be an upper limit above which reader performance deteriorates in terms of lower cancer-detection rates. With the imminent expansion of the programme, this has implications for service quality. These higher-volume readers should be encouraged to recall more borderline cases to assessment. Analysis of national data is recommended to further evaluate these findings.

CT staging of loco-regional breast cancer recurrence. A worthwhile practice?

AIMS: To assess the usefulness of computed tomography of the chest, abdomen, and pelvis (CTCAP) in the detection of metastatic disease in patients presenting with loco-regional recurrence of breast cancer, and to identify subgroups particularly likely to have metastases. MATERIALS AND METHODS: Over a 32-month period, 63 patients with 65 recurrences underwent CTCAP, and were identified from the hospital's computerized radiology system. RESULTS: Twenty-one patients (32%) had metastases, including bony (n=5, 8%), liver (n=7, 11%), and thoracic disease (n=11, 17%). Patients with recurrence in a conserved breast had lower rates of metastasis on CT than those with other sites of recurrence [three of 21 (14%) versus 18 of 44 (41%), p=0.03]. Patients younger than 50 years at primary diagnosis or younger than 60 years at recurrence had statistically significantly higher rates of metastasis than older patients [10 of 16 (63%) versus 11 of 48 (23%), p=0.003, and 13 of 23 (57%) versus eight of 42 (19%), p=0.002, respectively]. CONCLUSION: CT staging of patients presenting with loco-regional recurrence of breast cancer is a worthwhile practice. Younger patients and those with recurrence other than in the conserved breast are particularly likely to have metastatic disease.

Body weight reduction in rats by oral treatment with zinc plus cyclo-(His-Pro).

BACKGROUND AND PURPOSE: We have previously shown that treatment with zinc plus cyclo-(His-Pro) (CHP) significantly stimulated synthesis of the insulin degrading enzyme and lowered plasma insulin and blood glucose levels, alongside improving oral glucose tolerance in genetically type 2 diabetic Goto-Kakizaki (G-K) rats and in aged obese Sprague-Dawley (S-D) rats. Thus, we postulated that zinc plus CHP (ZC) treatment might also improve body weight control in these rats. We therefore determined the effects of ZC treatment on body weights in both genetically diabetic, mature G-K rats and non-diabetic, obese S-D rats. EXPERIMENTAL APPROACH: G-K rats aged 1.5-10 months and non-diabetic overweight or obese S-D rats aged 6-18 months were treated with 0-6 mg CHP plus 0-10 mg zinc L(-1) drinking water for 2-4 weeks, and changes in weight, serum leptin and adiponectin levels, food and water intakes were measured. KEY RESULTS: The optimal dose of CHP (in combination with zinc) to reduce weight and plasma leptin levels and to increase plasma adiponectin levels was close to 0.1 mg kg(-1) day(-1), in either mature G-K rats and aged overweight or obese S-D rats. Food and water intake significantly decreased in ZC treated rats in both aged S-D rats and mature G-K rats, but not in young S-D and G-K rats. CONCLUSIONS AND IMPLICATIONS: ZC treatment improved weight control and may be a possible treatment for overweight and obesity.

Does computer-aided detection have a role in the arbitration of discordant double-reading opinions in a breast-screening programme?

AIMS: To investigate whether a computer-aided detection (CAD) system could act as an arbitrator of discordant double-reading opinions, replacing the need for an independent third film reader. METHODS: The mammograms of the 240 women that underwent arbitration by an independent third reader were identified from the 16,629 women attending our screening centre between July 2003 and April 2004. Mammograms of the arbitration cases were digitized and analysed by a CAD system. To assess the ability of CAD to act as the arbitrator, the site of the CAD prompts was retrospectively compared to the site of any abnormality noted by the original film readers. If a CAD prompt was placed on a region marked by one of the film readers then the decision of CAD as the arbitrator was that the women should be recalled for further assessment. If no mark was placed then the region was considered low risk and the decision was not to recall. The decision of CAD as the arbitrator was retrospectively compared with the original recall decision of the independent third reader. RESULTS: There were 21 cancer cases in the group of women undergoing arbitration, diagnosed both at the original screening episode and subsequently. The independent third reader recalled 15/18 (83%) of the cancers that corresponded with the arbitrated lesion. CAD as the arbitrator would have recalled 16/18 (89%) of the cancers that corresponded to the arbitrated lesion. CAD acting as the arbitrator would have resulted in a significant increase in normal women being recalled to assessment in the arbitration group (P<0.001). The extra 50 recalls would have potentially increased the overall recall rate to assessment from 3.1 to 3.4%; a relative increase of 10%. CONCLUSIONS: The main effect of CAD acting as an arbitrator of discordant double-reading opinions is to increase the recall rate, significantly above what is found when arbitration is performed by an independent third reader. Using CAD as an arbitrator may be an option to deal with discordant double-reading opinions when no other method of consensus or arbitration is available.

Can computerised tomography replace bone scintigraphy in detecting bone metastases from breast cancer? A prospective study.

BACKGROUND: The aim of this study was to determine whether bone scans (BS) can be avoided if pelvis was included in CT thorax and abdomen to detect bony metastases from breast cancer. MATERIALS AND METHODS: Results of 77 pairs of CT (thorax, abdomen, and pelvis) and BS in newly diagnosed patients with metastatic breast cancer (MBC) were compared prospectively for 12 months. Both scans were blindly assessed by experienced radiologists and discussed at multidisciplinary team meetings regarding the diagnosis of bone metastases. RESULTS: CT detected metastatic bone lesions in 43 (98%) of 44 patients with bone metastases. The remaining patient had a solitary, asymptomatic bony metastasis in shaft of femur. BS was positive in all patients with bone metastases. There were 11 cases of false positive findings on BS. CONCLUSION: Our findings suggest routine BS of patients presenting with MBC is not required if CT (thorax, abdomen, and pelvis) is performed.

The pathological and radiological features of screen-detected breast cancers diagnosed following arbitration of discordant double reading opinions.

AIM: To compare the mammographic background pattern, the mammographic and the pathological features of screen-detected cancers diagnosed following arbitration of discordant double reading opinions with screen-detected cancers diagnosed following concordant double reading. METHODS: Between April 2002 and December 2003, 249 patients were diagnosed with screen-detected malignancies following concordant double reading. In the same period 38 patients were diagnosed with screen-detected malignancies after their mammograms had undergone arbitration prior to recall. Mammograms of both groups of patients were reviewed retrospectively and the mammographic features documented. Histological data for both groups were also compared. RESULTS: Cancers detected following arbitration were more likely to manifest as parenchymal distortions (44 versus 8%, p<0.001) and less likely to manifest as spiculate masses (19 versus 42%, p=0.014). Arbitration cancers were less likely to be detected in fatty breasts (4 versus 29%, p=0.01). Arbitration cancers were smaller (p=0.045). Lobular cancers were commoner in the arbitration group, although this was of borderline significance (19 versus 8%, p=0.057) There was no significant difference in patient age, tumour grade or lymph node stage between the two groups. CONCLUSION: Cancers detected following arbitration are smaller and more likely to manifest as a parenchymal distortion compared with cancers detected by both readers. Arbitration cancers have broadly similar prognostic features to cancers detected by concordant double reading. It is estimated that approximately 11% more cancers are detected as a result of double reading with arbitration compared with single reading alone, after taking into consideration second reader bias.