Katy Hogben

[11C]Choline Positron Emission Tomography in Estrogen Receptor–Positive Breast Cancer

Purpose: Novel radiotracers could potentially allow the identification of clinically aggressive tumor phenotypes. As choline metabolism increases during malignant transformation and progression of human mammary epithelial cells, we examined the ability of [11C]choline (CHO) positron emission tomography imaging to detect clinically aggressive phenotype in patients with estrogen receptor (ER)–positive breast cancer in vivo. Experimental Design: CHO positron emission tomography was done in 32 individuals with primary or metastatic ER–positive breast cancer. Semiquantitative (standardized uptake value) and fully quantitative (net irreversible transfer rate constant of CHO, Ki) estimates of CHO uptake in the tumors were calculated and compared with tumor grade, size, involved nodes, and also ER, progesterone receptor, Ki-67, and human epidermal growth factor receptor-2 scores. Results: Breast tumors were well visualized in 30 of 32 patients with good tumor background ratios. A wide range of uptake values were observed in primary and metastatic tumors. CHO uptake variables correlated well with tumor grade. For most imaging variables, a poor association was found with tumor size, ER, progesterone receptor, human epidermal growth factor receptor-2, Ki-67, and nodal status. Conclusions: CHO showed good uptake in most breast cancers and merits further investigation as a breast cancer imaging agent. (Clin Cancer Res 2009;15(17):5503–10)

The role of SRC-3 in human breast cancer

Members of the nuclear receptor superfamily are ligand-regulated transcription factors involved in the control of a broad range of normal physiological and disease processes. The estrogen receptor alpha (ERα) is a member of the steriod receptor family, which is part of the nuclear receptor superfamily. ERα it is important for many biological processes and plays a key role in the pathogenesis of breast cancer. Gene regulation by ERα requires the recruitment of a multitude of transcriptional co-regulators to the promoters of estrogen-responsive genes. There is evidence in support of the involvement of these co-regulators in breast cancer progression. We review the role of steroid receptor co-activator-3 (SRC-3), which is frequently amplified in breast cancer, and its role in breast cancer risk, outcome and response to endocrine therapy in patients with breast cancer.

Biological basis of [11C]choline-positron emission tomography in patients with breast cancer: comparison with [18F]fluorothymidine positron emission tomography

ObjectiveThe biological significance of [11C]choline (CHO) uptake in human tumours is unclear and probably linked to choline kinase-&agr; (CHK&agr;) expression and cell proliferation. We directly compared CHO with [18F]fluorothymidine (FLT), an imaging biomarker of proliferation, by positron emission tomography (PET) in patients with breast cancer to investigate whether cell proliferation is an important determinant of CHO uptake. Furthermore, we evaluated CHK&agr; and the Ki67-labelling index (LIKi67) in tumour biopsies. MethodsSequential CHO-PET and FLT-PET within the same imaging session were performed in 21 patients with oestrogen receptor (ER)-positive breast cancer (28 lesions). Average and maximum CHO standardized uptake values (SUV) at 60 min: SUV60,av, and SUV60,max, and the rate constant of net irreversible uptake, Ki, were compared with FLT uptake at 60 min: SUV60,av and SUV60,max. Biopsies were stained for CHK&agr; and LIKi67 in eight cases. ResultsTumours were equally visible on CHO-PET and FLT-PET imaging. Tumour CHO-PET strongly correlated with FLT imaging variables (Pearson’s r=0.83; P<0.0001 for CHO-SUV60,max vs. FLT-SUV60,max). A statistically significant association was found between CHO-PET variables and categorical scores of cytoplasmic CHK&agr; intensity and between FLT-PET and LIKi67 (P<0.05, one-way analysis of variance). ConclusionCholine metabolism and proliferation as assessed by PET were correlated in ER-positive breast cancer, indicating that high CHO uptake is a measure of cellular proliferation in this setting. CHO uptake was also found to be related to cytoplasmic CHK&agr; expression.

Management and outcome of HER2-positive early breast cancer treated with or without trastuzumab in the adjuvant trastuzumab era.

BACKGROUND Adjuvant trastuzumab (AT) is known to significantly improve survival of women with HER2(+) early breast cancer. This study explores the use and nonuse of AT in early breast cancer, as well as the efficacy in a neoadjuvant and adjuvant population, within a routine clinical setting. PATIENTS AND METHODS Histopathology reports of invasive breast cancer resected at Imperial College Healthcare NHS Trust (ICHT) between January 2006 and December 2008 were reviewed. HER2(+) patients were identified and their case notes reviewed. In addition, patients who received AT at our center but underwent surgery elsewhere were included in the efficacy and safety analyses. RESULTS The local HER2(+) rate was 13.1%, with 54.5% of these patients receiving AT. A total of 128 patients received AT (85 local and 43 referrals from elsewhere). Neoadjuvant chemotherapy (CT) followed by postoperative AT was associated with a significantly increased risk of recurrence compared with adjuvant CT and then AT (hazard ratio [HR] 18.6 [95% CI, 1.8-152.2]; P = .013). The proportion of patients who were disease free at 3 years from primary therapy was 96.4% (95% CI, 89.8%-100%) for adjuvant therapy, compared with 72.0% (95% CI, 56.5%-91.6%) for neoadjuvant therapy. AT was omitted in 49 HER2(+) patients; the main reason for AT omission was clinical judgment that the breast cancer was low risk. Patients treated with AT had a significantly decreased risk of recurrence (HR 0.27 [95% CI, 0.08-0.97]; P = .04) compared with the untreated patients. The majority of untreated relapses were in patients in whom there was an original intent to use AT. The proportion alive at 3 years for adjuvant CT, neoadjuvant CT, and untreated AT was 100%, 74.5%, and 92.7% respectively. CONCLUSION The overall efficacy and safety of AT in our routine clinical setting is comparable to the large randomized trials. HER2(+) patients who underwent neoadjuvant CT had a significantly increased risk of disease recurrence compared with patients treated with adjuvant CT followed by trastuzumab. Untreated patients had an increased risk of recurrence.

The importance of a medical chaperone: a quality improvement study exploring the use of a note stamp in a tertiary breast surgery unit

Objectives The project aim was to determine current use and documentation of medical chaperones within a major breast service unit. It explored ways of improving adherence to professional guidelines concerning chaperones. Setting The single centre quality improvement project was completed in a tertiary breast service unit in North West London. It was a three-stage project with initial audit in October 2013, 1st postintervention cycle in November 2013 and 2nd postintervention cycle in October 2014. Participants In each study cycle, data were collected from entries in clinic notes until at least 155 encounters with documented clinical examination were analysed. All notes were of female patients. Interventions (1) Intervention 1st cycle: presentation and discussion of chaperone guidelines alongside reminder posters and introduction of note stamp. (2) Intervention 2nd cycle: note stamp alone. Primary and secondary outcome measures Documentation of chaperone offer, documentation of patient preference regarding chaperone, identifier (name or signature) of chaperone present and gender of examining clinician. Results In the 1st postintervention cycle, 69.95% documentation of chaperone offer was recorded, p<0.001, CI (59.04% to 80.76%). This result was replicated in the 2nd postintervention cycle a year later with 74.86% documentation of chaperone offer recorded, p<0.001, CI (66.41% to 83.31%). The 4.91% difference was insignificant; p=0.294, CI (14.03% to 4.21%). Conclusions The authors suggest that a proforma approach to medical chaperones is an effective means of ensuring adherence to best practice guidelines. A stamp, or similar, that can be embedded into documentation structure is an effective example of such an approach. Improved documentation allows any problems with adherence to guidelines to be more easily identified, helping to ensure the safeguarding of patients and staff involved in intimate examinations.

Best-practice care pathway for improving management of mastitis and breast abscess: Management of mastitis and breast abscess

Surgical subspecialization has resulted in mastitis and breast abscesses being managed with unnecessary admission to hospital, prolonged inpatient stay, variable antibiotic prescribing, incision and drainage rather than percutaneous aspiration, and loss to specialist follow‐up. The objective was to evaluate a best‐practice algorithm with the aim of improving management of mastitis and breast abscesses across a multisite NHS Trust. The focus was on uniformity of antibiotic prescribing, ultrasound assessment, admission rates, length of hospital stay, intervention by aspiration or incision and drainage, and specialist follow‐up.

P2-15-02: Are We Performing More Mastectomies on Women Diagnosed with Invasive Breast Cancer?

Introduction: Surgical management of breast cancer has changed over the past several decades; breast-conserving surgery has become widely accepted. Mastectomies, however, are still being performed as part of the management of breast cancer. The aim of this study was to investigate the indications for mastectomy in women with invasive breast cancer within our institution. Method: A systematic review of all new patients with invasive breast cancer treated with surgical intervention at our breast unit in the years 2000, 2005 and 2009 was performed. Using our databases, patient demographics, tumour characteristics and reasons for mastectomy were examined. Screen-detected and symptomatic patients were included in the study. Patients excluded were those with incomplete data and recurrent breast cancer. Results: A total of 584 patients (F:M, 576:8); with cancer types which included invasive ductal carcinoma (n=501, 84%), invasive lobular carcinoma (n=51, 9%), invasive tubular carcinoma (n=27, 5%) and sarcomas (n=5, 1%) were studied. Conclusion: In our institution, the majority of patients with screen-detected invasive breast cancer fulfilled the criteria to have breast-conserving surgery; mastectomy rate for screen-detected cancers remained stable. However, we found that in the symptomatic patient group, there was an increase in mastectomy rate from 16% (n=170) in 2000 to 52% (n=225) in 2009. Despite this trend, our results were still in keeping with the national standard as illustrated by the National Cancer Intelligence Network, where they noted that in 2006, 52% of symptomatic patients with invasive breast cancer underwent mastectomy in the United Kingdom. The reason for a higher mastectomy rate in symptomatic patients compared to screen-detected patients in 2009 is multifactorial. We found that a larger proportion of symptomatic patients presented with larger tumours and tumours which were multifocal in nature. Other factors which may have contributed included more accurate estimation of tumour size by imaging (e.g. MRI) and patient choice. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-02.

P2-14-10: Are There Variations in Invasive Tumour Characteristics between Different Ethnic Groups?

Introduction: Studies have shown that ethnic minorities with breast cancer are more likely to present at a younger age and with more aggressive tumours. The aim of this study was to examine the variation in tumour characteristics and surgical outcomes in different ethnic groups in our breast unit over a 12-month period. Methods: A retrospective study was performed on all patients with a new diagnosis of breast cancer, either screen-detected or symptomatic, between January to December 2009. Using our Trust databases, data on patient demographics, tumour characteristics, and ethnicity were collected. Where ethnicity was not documented, patients were contacted by telephone to complete the database. Those unable to be contacted were excluded from the study. Other exclusion criteria include those with recurrent ipsilateral breast cancer. Results: A total of 270 patients (265 females) were included in our study, of which 235 (87%) had invasive cancers (ductal carcinoma, lobular carcinoma, tubular carcinoma, mucinous carcinoma, cribriform carcinoma, papillary carcinoma, sarcoma) and the remaining 35 patients (13%) had non-invasive cancers (ductal carcinoma in-situ, lobular carcinoma in-situ, papilloma, columnar cell hyperplasia). We were unable to contact 23 (8.5%) patients to ascertain their ethnicity, and therefore these have been excluded from our results. Table 1. Tumour characteristics and surgical intervention in patients with invasive breast cancer in 2009 Conclusion: We found that the age of breast cancer presentation was lowest in Black and Asian patients (mean age 52 years and 54 years, respectively), compared to White (mean age 59 years). Furthermore, compared to white patients, tumours in Asian patients were larger (62.5% vs 47.2%), of higher grade (83.3% vs 75.2%), more likely to be ER negative (16.7% vs 12.4%), and tended to be lymph node positive (41.7% vs 34.2%). These may explain the higher mastectomy rate in Asian patients (n=12, 50%). The reason for the younger presentation age in the ethnic Asian group is unclear. However, it is possible that their cancer may have different tumour biology. Other studies have suggested reasons such as birth cohort effect and obesity. Reflecting the United Kingdom9s population the majority of patients that present to our breast unit are White and the number of Asian patients remains small. An increase in the sample size may strengthen our results. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-14-10.

P5-21-04: Patient Attitudes towards Undergoing Additional Breast Biopsy for Research Purposes.

Background Acquisition of additional breast tissue for research has become integral to breast oncology research but no data exists regarding patient attitudes to additional, non-diagnostic biopsies. Baseline research biopsies may be obtained as part of the diagnostic process as extra passage(s) of the needle through a ‘generic consent’ process, or as an additional biopsy event after carcinoma diagnosis has been confirmed and eligibility for a specific study has been established. This study sought to explore patient perspectives to such biopsies. Patients and Methods Patients attending breast clinics were recruited to complete a questionnaire prior to their consultation (and any interaction with researchers or clinicians seeking consent for research biopsies) which examined willingness to undergo an extra fine needle aspirate (FNA) and/or core needle biopsy (CNB) for research either at time of the diagnostic biopsy (B1) or after diagnosis (B2). Descriptions of FNA and CNB procedures were supplied to those with no prior experience. Patient perspectives towards donating surplus tissue left over from a diagnostic procedure and/or surgery for storage for future research was also explored. Results : 100 patients were recruited, 42% with a prior history of breast carcinoma, 23% with family history of breast carcinoma and 65%/ 42% with previous experience of CNB/FNA respectively for either benign or malignant disease. Willingness to undergo additional biopsy was greater for the B1 than the B2 time point, but equivalent for CNB and FNA (willingness CNB B1 50% vs B2 26%, willingness FNA B1 50% vs B2 29%). A statistically significant increase in willingness to undergo CNB and FNA at B1 and/or B2 was seen in association with prior diagnosis of breast cancer, family history of breast cancer, previous visit to breast clinic and prior experience of breast biopsy. Reasons for willingness or unwillingness were recorded. 83% of patients expressed a willingness to allow surplus tissue to be stored in a biobank for future research. Conclusions : When asked by questionnaire prior to clinic consultation, additional research biopsy was much more acceptable if undertaken at time of initial diagnostic biopsy rather than at a later time point. Acceptability was equivalent for CNB and FNA. Previous experience of biopsy, previous attendance to breast clinic, a prior history of breast cancer or family history of breast cancer increased acceptability suggesting that willingness is increased with knowledge of the biopsy procedure. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-21-04.