Nigel Barrett

Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal-growth-factor-receptor-positive primary breast cancer: a double-blind placebo-controlled phase II randomised trial.

BACKGROUND Some oestrogen-receptor (ER) positive breast cancers express epidermal growth factor receptor (EGFR), but whether inhibition of EGFR can suppress proliferation of breast cancer cells and ER function is not known. METHODS In a double-blind, placebo-controlled randomised trial of 56 postmenopausal patients with ER-positive and EGFR-positive primary breast cancer, 27 women were randomly assigned to the tyrosine-kinase inhibitor of EGFR gefitinib (250 mg given orally once a day) and the aromatase inhibitor anastrozole (1 mg given orally once a day), and 29 women to gefitinib (250 mg given orally once a day) and placebo of identical appearance to anastrozole given orally once a day, all given for 4-6 weeks before surgery. Primary outcome was inhibition of tumour-cell proliferation, as measured by Ki67 antigen labelling index. Secondary outcomes were reduction in EGFR phosphorylation at Tyr 845, reduction in ER phosphorylation at Ser 118, tumour size, and toxic effects. Analyses were by intention to treat. FINDINGS Patients assigned gefitinib and anastrozole had a greater reduction from pretreatment values in proliferation-related Ki67 labelling index than did those assigned gefitinib alone (mean % reduction 98.0 [95% CI 96.1-98.9] vs 92.4 [85.1-96.1]; difference between groups 5.6% [5.1-6.0], p=0.0054). Tumour size was reduced by 30-99% (partial response) in 14 of 28 patients assigned gefitinib and [corrected]in 12 of 22 assigned gefitinib, as assessed by ultrasonography. Reduction in phosphorylation of ER at Ser 118 was similar for both groups. Treatment was well tolerated and much the same for both groups. INTERPRETATION Single-agent gefitinib and gefitinib combined with anastrozole are well-tolerated and effective treatments for reducing the size of breast tumours and levels of ER phosphorylation when given as neoadjuvant therapy.

Influence of personal characteristics of individual women on sensitivity and specificity of mammography in the Million Women Study: cohort study

Abstract Objectives To examine how lifestyle, hormonal, and other factors influence the sensitivity and specificity of mammography. Methods Women recruited into the Million Women Study completed a questionnaire about various personal factors before routine mammographic screening. A sample of 122 355 women aged 50-64 years were followed for outcome of screening and incident breast cancer in the next 12 months. Sensitivity and specificity were calculated by using standard definitions, with adjustment for potential confounding factors. Results Breast cancer was diagnosed in 726 (0.6%) women, 629 in screen positive and 97 in screen negative women; 3885 (3.2%) were screen positive but had no subsequent diagnosis of breast cancer. Overall sensitivity was 86.6% and specificity was 96.8%. Three factors had an adverse effect on both measures: use of hormone replacement therapy (sensitivity: 83.0% (95% confidence interval 77.4% to 87.6%), 84.7% (73.9% to 91.6%), and 92.1% (87.6% to 95.0%); specificity: 96.8% (96.6% to 97.0%), 97.8% (97.5% to 98.0%), and 98.1% (98.0% to 98.2%), respectively, for current, past, and never use); previous breast surgery v no previous breast surgery (sensitivity: 83.5% (75.7% to 89.1%) v 89.4% (86.5% to 91.8%); specificity: 96.2% (95.8% to 96.5%) v 97.4% (97.3% to 97.5%), respectively); and body mass index < 25 v ≥ 25 (sensitivity: 85.7% (81.2% to 89.3%) v 91.0% (87.5% to 93.6%); specificity: 97.2% (97.0% to 97.3%) v 97.4% (97.3% to 97.6%), respectively). Neither sensitivity nor specificity varied significantly according to age, family history of breast cancer, parity, past oral contraceptive use, tubal ligation, physical activity, smoking, or alcohol consumption. Conclusions The efficiency, and possibly the effectiveness, of mammographic screening is lower in users of hormone replacement therapy, in women with previous breast surgery, and in thin women compared with other women.

An ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis.

Advances in the management of the pulmonary complications of cystic fibrosis may result in an increasing prevalence of patients with chronic liver disease which may, therefore, become more important in the long-term management of cystic fibrosis patients. However, no simple and reliable test is available for the diagnosis of liver disease in cystic fibrosis. In particular percutaneous liver biopsy is highly inaccurate and potentially dangerous. Imaging techniques, including real-time ultrasound scanning, have been used to evaluate the hepato-biliary system in cystic fibrosis and may represent the best available techniques for documenting hepatic involvement. The purposes of this study were to construct an ultrasound scoring system using three cardinal features of hepatic ultrasound in cystic fibrosis: coarseness of the parenchyma, nodularity of the liver edge and increased periportal echogenicity, to enable the accurate, early diagnosis of liver involvement in cystic fibrosis. The scoring system was validated by correlating the results against ultrasound markers of portal hypertension, clinical and haematological data. The scoring system proved to be reproducible and to correlate well with the markers of hepatic disease detailed above. The results also suggest that the scoring system may allow the identification of patients with pre-cirrhotic chronic liver disease and so may prove of value in selecting a sub-group of patients more likely to respond to therapy.

Impact of use of hormone replacement therapy on false positive recall in the NHS breast screening programme: results from the million women study

About half of the women attending the NHS breast screening programme have used hormone replacement therapy.1 Although previous studies have reported that use of hormone replacement therapy increases the risk of being recalled after mammography for further assessment, with no subsequent diagnosis of breast cancer (“false positive recall”), the effect of different patterns of use is unclear.2 Relative risk of false positive recall in postmenopausal women in relation to time since last use of hormone replacement therapy. (Relative risk compared with never users (1057/44 427 recalled) stratified by screening centre, age, previous screening, body mass index, previous breast operation, and time since menopause in: current users of hormone replacement therapy (relative risk 1.64, 95% confidence interval 1.50 to 1.80; 1157/28 634 recalled); past users ceasing use <1 year ago (1.42, 1.08 to 1.86; 63/1758 recalled), 1-4 years ago (1.23, 1.04 to 1.46; 176/5910 recalled), and ≥5 years ago (1.07, 0.85 to 1.34; 92/3800 recalled)). Results are plotted according to the median number of years since last use of hormone replacement therapy in each of these categories From June 1996 to March 1998, 87 967 postmenopausal women aged 50-64 invited to routine …

Predictors of outcome of mammography in the National Health Service Breast Screening Programme.

BACKGROUND: Little is known about the factors influencing the risk of recall for assessment, invasive diagnostic procedures, and early rescreening after screening mammography. METHODS: From June 1996 to March 1998 women attending screening at 10 National Health Service Breast Screening Programme (NHSBSP) centres completed a self administered questionnaire and were followed up for their screening outcome. RESULTS: 1969 (3.3%) out of 60 443 women aged 50–64 who had never used hormone replacement therapy (HRT) were recalled for assessment but were not diagnosed with breast cancer (defined here as false positive recall). After adjustment for the variation between centres, false positive recall was decreased significantly among women who were likely to have had a previous NHSBSP mammogram (odds ratio (OR) 0.49, 95% confidence interval (95% CI) 0.38 to 0.63 for likely versus unlikely), who were postmenopausal (OR 0.65, 95% CI 0.56 to 0.76 for postmenopausal v premenopausal) and increased significantly for women reporting previous breast surgery (OR 1.64, 95% CI 1.42 to 1.89). Although false positive recall decreased significantly with parity and increasing body mass index, these effects were not large and no significant variation was found with age, education, family history of breast cancer, oral contraceptive use, sterilisation, exercise, smoking, or alcohol consumption. Altogether 655 (1.1%) women had an invasive diagnostic procedure; no personal characteristics were predictive of this outcome, 286(0.5%) were referred for early rescreening, and this was increased significantly by nulliparity and a family history of breast cancer. INTERPRETATION: Premenopausal women, those without a previous NHSBSP mammogram, and women with previous breast surgery have an increased risk of false positive recall by the NHSBSP.

Audit of wide bore needle biopsies graded B3: does the final pathology justify the increasing rate of benign biopsy?

A recent national audit of the West of London Breast Screening Service showed an increased rate of benign biopsy. This may be related to the increasing rate of wide bore needle (WBN) biopsies graded as B3 (indeterminate). Common B3 pathologies include atypical ductal hyperplasia (ADH), columnar cell change with hyperplasia or atypia (CCC) and intraduct papilloma (IP). Previous studies have shown an association of these lesions with malignancy [1,2]. Our practise is to recommend excision biopsy of these B3 lesions. We retrospectively audited surgical excision biopsies of B3 lesions between April 2004 and April 2005, recording mammogram findings, patient demographics, WBN and surgical excision pathological diagnoses. Twenty-five women age 50–70 (mean age 58) had excision biopsy of their B3 lesions; 64% were microcalcifications, 28% masses and the remainder distortions. The 14G core biopsy pathology included 38% ADH, 16% atypical lobular hyperplasia, 16% CCC and 12% IP. The surgical excision pathology available in 14 of these women showed ductal carcinoma in situ in seven and invasive ductal carcinoma in situ in three, justifying our practise. We discuss how the surgical pathology correlates with that of the WBN.

PB.32: Does vacuum-assisted biopsy decrease the B3 rate in stereotactic biopsy of breast lesions?

Vacuum-assisted biopsy (VAB) systems have been shown to outperform 14G core needle biopsy (CNB) reducing the need for diagnostic or multiple surgeries. We introduced VAB in 2011 with the aim of reducing our B3 rate and increasing rate of preoperative diagnosis of invasive cancer.