Mastitis and Mammary Abscess Management Audit (MAMMA) in the UK and Ireland.

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. CONCLUSIONS: Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.

Mastitis and breast abscess is a painful infection of the breast. It is an extremely common breast problem. One in three women can get this condition at some stage in their life. To treat a breast abscess, the pus inside should be drained out of the body. This can be done either by cutting into the breast using surgery or by inserting a fine needle using an ultrasonography scan (which uses ultrasound). Fine-needle drainage has the benefit that it does not require admission to hospital. Surgery can cause the breast to look misshapen. It is unknown which method is used more often in the UK and Ireland. The aim of this study was to describe how mastitis and breast abscesses are treated in the UK and Ireland. This study involved a survey of practice (phase 1) and collection of data, which are routinely recorded for these patients (phase 2). This study involved 69 hospitals and 1312 patient records. One in five women had an operation for a breast abscess. This was higher than expected. Six in 10 women had a pus drainage using a fine needle. The chance of having an operation depended on the hospital. Women that came to hospital at the weekend were almost twice as likely to have an operation. One in five women were admitted to hospital. The chances of that more than doubled if a woman came to hospital at the weekend. There are differences in treatment of mastitis and breast abscesses across the UK and Ireland. Changes need to be put in place to make access to treatment more equal.

Test, evidence, transition projects in Scotland: developing the evidence needed for transition of effective interventions in cancer care from innovation into mainstream practice.

BACKGROUND: A robust evidence base is required to assist healthcare commissioners and providers in selecting effective and sustainable approaches to improve cancer diagnosis and treatment. Such evidence can be difficult to build, given the fast-paced and highly pressured nature of healthcare delivery, the absence of incentives, and the presence of barriers in conducting pragmatic yet robust research evaluations. Cancer Research UK (CRUK) has played an active part in building the evidence base through its funding of programmes to identify, evaluate and scale-up innovative approaches across the UK. The aim of this paper is to describe and explain the research design and intended approach and activities for two cancer services improvement projects in Scotland funded by CRUK. METHODS: A hybrid effectiveness-implementation study design will assess both the efficiency of the new pathways and their implementation strategies, with the aim of generating knowledge for scale-up. A range of implementation, service and clinical outcomes will be assessed as determined by the projects' Theories of Change (ToCs). A naturalistic case study approach will enable in-depth exploration of context and process, and the collection and synthesis of data from multiple sources including routine datasets, patient and staff surveys, in-depth interviews and observational and other data. The evaluations are informed throughout by a patient/public representatives' group, and by small group discussions with volunteer cancer patients. DISCUSSION: Our approach has been designed to provide a holistic understanding of how (well) the improvement projects work (in relation to their anticipated outcomes), and how they interact with their wider contexts. The evaluations will help identify barriers, facilitators, and unanticipated consequences that can impact scalability, sustainability and spread. By opting for a pragmatic, participatory evaluation research design, we hope to inform strategies for scaling up successful innovations while addressing challenges in a targeted manner.

Imprint cytology from core biopsies increases the sensitivity of fine needle aspiration (FNA) in breast cancer patients.

BACKGROUND: Fine needle aspiration cytology (FNAC) can have high inadequate results. The main objective of this study was to validate the sensitivity of imprint cytology and compare it to that of FNAC across all levels of staff experience. Our other objective was to find out whether handling of a core biopsy to obtain an imprint slide affected its morphology so as to make histopathological reporting from that tissue difficult. This we thought could be of significance while trying to diagnose smaller cancers where just one core could contain tumour. METHODS: Patients (n = 56) with a suspicious breast lump had fine needle aspiration (FNA) and core biopsy. The core biopsy used to prepare the two imprint cytology slides was sent separately for histopathology reporting. RESULTS: Simultaneous imprint cytology from a core biopsy increased the sensitivity of cytology results by 12% compared to that of FNAC alone. In this series we found imprint cytology to have a sensitivity of 84%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 82.7%. The histopathologists did not report any distortion in tissue morphology so as to affect histological reporting of the core used. CONCLUSION: Since most patients will have a core biopsy to confirm invasive cancer and the technique of imprint cytology is easily performed, perhaps it should be more widely used especially in units where the sensitivity of FNA is low.

Anastrozole and letrozole: an investigation and comparison of quality of life and tolerability.

Previous studies have demonstrated that both anastrozole and letrozole are well tolerated. Letrozole suppresses estrogen to a greater degree than anastrozole in the serum and breast tumor. Concerns have been raised that greater potency may adversely affect patients' quality of life (QOL). One hundred eighty-one postmenopausal women with invasive estrogen receptor-positive breast cancers were randomized to receive either 12 weeks of letrozole followed by 12 weeks of anastrozole or the reverse sequence. One hundred and six received immediate adjuvant aromatase inhibitors (AIs) following surgery, and 75 received extended adjuvant therapy. The Functional Assessment of Cancer Therapy Endocrine Subscale (FACT-B-ES) QOL questionnaires were completed to assess QOL on each drug. Additional side-effect profiles were collected. Each patient completed a patient preference form. Twenty-one patients withdrew before study end, 10/179 (5.6%) while taking letrozole and 4/173 (2.3%) while taking anastrozole (P = 0.12). Tamoxifen-naïve patients had a higher mean ES (endocrine symptoms subscale) score at entry versus those having extended therapy (66.0 vs. 61.9; P = 0.001). There was no significant change in FACT-B-ES (overall) scores or ES scores while patients were taking anastrozole or letrozole and no significant differences between drugs. Nearly 80% of patients reported one or more side effects with either agent. No differences in frequency, grade, or range of side effects were seen between drugs. Of 160 patients, 49 (30.6%) preferred letrozole, 57 (35.6%) preferred anastrozole, and 54 (33.8%) had no preference (P = 0.26, Pearson's Chi-squared test). In conclusion, both AIs are equally well tolerated. There were no significant differences in QOL scores between the two drugs.

Short course pre-operative ferrous sulphate supplementation--is it worthwhile in patients with colorectal cancer?

INTRODUCTION: Pre-operative anaemia is well recognised in patients presenting with colorectal cancer (CRC). While the benefits of long-term FeSO4 supplementation on Fe deficiency anaemia are well established, it is not known if short-course supplementation (2-3 weeks) impacts significantly on pre-operative haemoglobin (Hb) levels. This study examines the impact of short-term, oral FeSO4 supplementation on patients undergoing surgery for CRC. PATIENTS AND METHODS: All patients with CRC presenting to a single surgeon were included. At diagnosis, baseline Hb and blood film were checked on all patients who then received 200 mg tds of FeSO4. Haemoglobin was rechecked pre-operatively and daily postoperatively. Patients requiring pre-operative blood transfusions were excluded from analysis. RESULTS: Between 1 January 2004 and 31 December 2006, 117 patients were identified, 14 of whom were excluded. Patients received a median of 39 days' treatment with FeSO4. Fifty-eight (56.3%) patients were anaemic at presentation gaining a mean of 1.73 g/dl (P<0.001) from short-course FeSO4 supplementation. Right-sided tumours (lower mean Hb at presentation; P=0.008) responded more to FeSO4 when compared to left-sided tumours (P<0.017). Increase in Hb was unrelated to pathological stage. The transfusion rate for all curative resections was 0.69 units/patient. For the historical cohort (patients undergoing curative resection between 1 January 2001 and 31 December 2003), the mean transfusion rate fell from 1.69 units/patient. CONCLUSIONS: Routine short-course supplementation with iron offers improved pre-operative Hb prior to surgery in CRC, especially in right-sided lesions and those with presenting anaemia.

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer.

ALIQUOT (Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer. Ninety-four patients were randomized to receive either 12 weeks of letrozole (2.5 mg; n = 42) followed by 12 weeks of anastrozole (1 mg), or 12 weeks of anastrozole (1 mg; n = 42) followed by 12 weeks of letrozole (2.5 mg). After completion of the study period, patients in the immediate adjuvant group were either switched to tamoxifen (n = 38) or continued on anastrozole or letrozole. In the beginning of the study, 42 patients had taken tamoxifen within 3 months. Patients taking drugs likely to affect bone metabolism, including bisphosphonates, were excluded. Eighty-four patients had complete sample measurements and were included in the analysis. Prior tamoxifen therapy resulted in a significantly lower mean baseline procollagen type 1 N-terminal propeptide (PINP) compared with patients with no prior tamoxifen. There were no significant differences in bone markers between AIs at any time. By 6 months, significant increases were seen in PINP, C-terminal telopeptides (CTX), bone specific alkaline phosphatise (ALP), and urinary N-terminal telopeptides (NTX). Patients with prior tamoxifen had significantly greater increases than patients with no prior tamoxifen. Patients treated with 3 months of tamoxifen following 6 months of an AI showed a significant decrease in markers of bone resorption, serum CTX and urinary NTX. In conclusion, AI-induced bone turnover increases over time. Anastrozole and letrozole produce similar effects on bone metabolism and turnover. Stopping tamoxifen therapy and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naïve patients. Patients given tamoxifen following AI therapy showed a decrease in markers of bone resorption.

Increase in response rate by prolonged treatment with neoadjuvant letrozole.

PURPOSE: The aim of this study was to investigate the potential benefits of prolonged treatment with neoadjuvant letrozole. PATIENTS AND METHODS: About 182 consecutive patients have been treated in Edinburgh with neoadjuvant letrozole for 3 months or longer and 63 patients have continued on letrozole beyond 3 months. Outcomes are reported. RESULTS: Of the 63 patients who continued on letrozole, 38 patients took letrozole for more than 1 year and 23 took letrozole for more than 24 months. The median reduction in clinical volume in the first 3 months in these 63 patients was 52%. Similar reductions in median clinical volume were seen between three to 6 months (50%), 6-12 months and 12-24 months (medians 37 and 33%, respectively). At 3 months 69.8% of the 182 patients had a partial or complete response. The response rate increased to 83.5% with prolonged letrozole treatment. Continuing letrozole beyond 3 months increased the number of women who initially required mastectomy or had locally advanced breast cancer who were subsequently suitable for breast conserving surgery from 60% (81/134) at 3 months to 72% (96/134). Thirty-three women remain on letrozole alone (man age at diagnosis 83 years) and at 3 years the median time to treatment failure has not been reached. CONCLUSION: Continuing letrozole in responding patients beyond 3-4 months achieves further clinical reduction in tumour size. For elderly women with a short life expectancy letrozole alone may provide long-term disease control.

Letrozole suppresses plasma estradiol and estrone sulphate more completely than anastrozole in postmenopausal women with breast cancer.

PURPOSE: To compare the effects of anastrozole and letrozole on plasma estradiol (E2) and estrone sulfate (E1S) levels. PATIENTS AND METHODS: Fifty-four postmenopausal women with estrogen receptor-positive breast cancer receiving aromatase inhibitors (AIs) as part of their adjuvant therapy were randomly assigned to receive either 3 months of anastrozole (1 mg) followed by 3 months of letrozole (2.5 mg), both given orally once daily, or 3 months of the opposite sequence. Blood was taken at the same time and the same day of the week from each patient, before and after 3 months of each drug, and plasma levels of E2 and E1S were determined using highly sensitive radioimmunoassays. RESULTS: There were 27 patients in each group. The mean age of the patients was 63 years (range, 49 to 83 years). Baseline E2 levels ranged from 3 pmol/L to 91 pmol/L with a mean of 25.7 pmol/L. Only one of 54 (2%) patients had an E2 value >or= 3 pmol/L after receiving letrozole, versus 20 of 54 (37%) patients after receiving anastrozole (P < .001). Extrapolation revealed a mean E2 level after anastrozole treatment of 2.71 pmol/L (range, 2.38 to 3.08 pmol/L). Following letrozole, it was 1.56 pmol/L (range, 1.37 to 1.78 pmol/L). Mean residual E2 was 10.1% for anastrozole and 5.9% for letrozole. Residual E1S levels were 4.6% for anastrozole and 2.0% for letrozole (P = .001). CONCLUSION: Letrozole reduces plasma E2 and E1S levels to a significantly greater extent than anastrozole in postmenopausal women taking AIs as part of their adjuvant therapy for hormone receptor-positive breast cancer.

Changes in breast cancer transcriptional profiles after treatment with the aromatase inhibitor, letrozole.

OBJECTIVE: The aim of the study was to identify changes in tumour expression profiling associated with short-term therapy of breast cancer patients with letrozole. EXPERIMENTAL DESIGN: Microarray analysis was performed on RNA extracted from paired tumour core biopsies taken before and after 14 days of treatment with letrozole (2.5 mg/daily) in 58 patients. Changes in expression profile were identified by three different approaches on the basis of frequency of changes, magnitude of changes and significance analysis of microarray. RESULTS: No single gene was consistently changed by therapy in all cases. Fifty-two genes, however, were downregulated and 36 upregulated in at least 45 of the 58 cases. In terms of quantitative change, 46 genes showed at least a median 1.5-fold change in expression. Significance analysis of microarray identified 62 genes that were significantly changed by therapy (P<0.0001, 56 downregulated and six upregulated). All three approaches showed that greater numbers of genes were downregulated rather than upregulated. Merging data produced a total of 143 genes, which were subject to gene ontology and cluster analysis. The ontology of the 91 downregulated genes showed that they were functionally associated with cell cycle progression, particularly mitosis. In contrast, upregulated genes were associated with organ development, connective tissue extracellular matrix regulation and inflammatory response. Cluster analysis segregated the patients into four groups differing in patterns of gene expression. CONCLUSION: Genes have been identified which either change markedly or consistently in breast cancer after 14 days treatment with letrozole. These are new important data in understanding letrozole's molecular mechanism of action in breast cancers.

DCIS and aromatase inhibitors.

In patients with hormone receptor positive DCIS tamoxifen reduces recurrence rates by almost 50%. Few data are available with aromatase inhibitors from randomised studies. In the ATAC study there were three DCIS lesions in the anastrozole arm and four in the tamoxifen arm in the women with ER positive invasive cancer. In the MA17 study which randomised patients to up to 5 years of letrozole or placebo there was only one DCIS event in the contralateral breast in patients taking letrozole and five on placebo. There were also four patients in this study who had DCIS in the conserved breast on placebo and none in the letrozole treated group. The few clinical data that are available therefore suggest the aromatase inhibitors are likely to be effective in DCIS. A histological review of a study of 206 postmenopausal women with invasive oestrogen receptor positive breast cancer who were randomised as part of a 14 day preoperative study to receive 2.5mg of letrozole or 1mg of anastrozole identified 27 patients with 28 pairs of tumours in whom there was sufficient ER positive DCIS in invasive cancer in the initial core biopsy and in the subsequent surgery specimen, to evaluate for PgR activity and proliferation. Within the DCIS both aromatase inhibitors significantly reduced PgR expression and both drugs also produced a significant fall in proliferation. There was a moderate degree of agreement between the fall in PgR in both the invasive cancer and DCIS (Kappa=0.5; p=0.0013) and between the fall in proliferation and between the invasive and in situ components (correlation coefficient=0.68; p<0.001). This study has shown significant effects of aromatase inhibitors on DCIS indicating that these agents are therapeutically active in this condition.

Neoadjuvant endocrine therapy models.

Neoadjuvant therapy is therapy administered before surgical intervention and while the tumor remains in the breast. It may be given to treat large, locally advanced tumors, with the aim of shrinking them and thus making their surgical excision either simply possible or less radical. Most neoadjuvant therapy is chemotherapy, but adjuvant endocrine therapy is increasingly used in hormone-sensitive tumors; for example, those responsive to tamoxifen. Repeat biopsies aimed at assessing response to treatment--for example, by examining estrogen receptor status or markers of proliferation in tumor tissue--may be taken during the course of adjuvant therapy. In this chapter, the essential protocols associated with designing neoadjuvant trials are described, methods of assessing response to neoadjuvant therapy are detailed, and various approaches to collecting appropriate clinical samples and their assessment are presented.

Surgical issues surrounding use of aromatase inhibitors.

There are important surgical issues related to the use of the third generation aromatase inhibitors in both the neoadjuvant and adjuvant settings. Neoadjuvant hormone therapy is effective at downstaging tumours, particularly large tumours initially thought to be inoperable or requiring mastectomy. Randomised trials have shown that the newer aromatase inhibitors letrozole and anastrozole increase the numbers of women who are suitable for breast-conservation compared with tamoxifen, and that letrozole is superior to tamoxifen in terms of clinical response. Aromatase inhibitors are most effective in ER-rich tumours and are clinically and biologically effective in both HER2 positive and negative tumours, whereas HER2 positive tumours show a level of resistance to tamoxifen. In neoadjuvant studies comparing aromatase inhibitors with tamoxifen, the duration of use has been 3-4 months, by which time any response is usually evident but longer treatment periods produce continued shrinkage and response. The re-excision rate following breast conservation surgery after neoadjuvant hormone therapy is favourable compared with the rates following immediate wide local excision. Local recurrence rates are acceptable in patients undergoing neoadjuvant therapy and breast-conserving surgery providing post-operative radiotherapy is given. Adjuvant aromatase inhibitors, as well as having an effect on metastatic disease and survival, reduce local and regional recurrence.