#5047 Background: The effect of primary breast tumours and their subsequent treatment on immune system function is still poorly understood and may have critical implications with regard to disease recurrence and success of treatment with the new generation of biologicals. In line with our interest in the expression and role of natural killer (NK) cell activating receptors, we measured the expression of NK cell surface receptors NKp30, NKp46 and NKG2D in patients with primary breast cancer. NKp30 and NKp46 are members of the natural cytotoxic receptors (NCRs) and are expressed on the majority of NK cells of healthy individuals. NKG2D is a member of the C type lectin superfamily. These receptors activate NK cells upon stimulation and are involved in NK cell tumour recognition and triggering although their ligands on tumour cells remain elusive.
 Methods: Our experimental procedure involved obtaining serial blood samples prior to and post surgery (4 hours-6 months) in patients with primary breast cancer. This allowed us to study basal levels of NK cell receptors as well as to investigate the effect of surgery and post surgery treatment on receptor expression. NK receptor analysis was performed on whole blood by three colour flow cytometry using antibodies against CD3, CD56 and the NK receptors with samples analysed on a FACSCalibur flow cytometer (BD).The data was analysed using CELLQuest.
 Results and Discussion: NK cells were defined as CD3-, CD56+ lymphocytes and their frequency, as measured by the three colour staining protocol, was broadly in agreement with the levels found using four colour antibody staining and Trucount tubes (BD). The majority of patients expressed NKp30, NKp46 and NKG2D at levels consistent with that seen in age and sex matched control samples obtained from healthy individuals. However, in a number of patients (10/30), the levels of NKp30 and NKp46 expression were low at all timepoints tested. The levels of NKp30 were generally lower than NKp46 and were unrelated to surgery. NKG2D expression was less affected with the levels similar to that found in controls individuals. The significance of these findings with respect to NK cell target recognition is unclear as an array of activating and inhibitory receptors are involved in NK cell activation and target recognition. This staining approach has also allowed us to assess the relative frequency of CD56dim and CD56bright NK cells. In healthy individuals the majority of NK cells are CD56dim whilst around 5% are CD56bright. These are considered to represent a functionally distinct population. In a number of patients in this study, the expression of CD56 on NK cells was relatively low with the consequential decrease in the frequency of CD56bright cells. We are prospectively following the importance of these NK cell differences with respect to patient health, and disease free and overall survival. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5047.
#1019 Introduction
 Sentinel lymph node biopsy is now standard practice in axillary staging in breast cancer. It is associated with less morbidity than an axillary node clearance. A drawback of sentinel node biopsy is the need for a second surgical procedure if the sentinel node shows metastases. Clinical examination of the axilla has been the standard pre-operative assessment but this has been shown to be unreliable. More recently ultrasound has been used to identify axillary metastases pre-operatively. The aim of our study is to assess the role of pre-operative ultrasound and fine needle aspirate cytology in refining the selection of patients for whom sentinel node biopsy is appropriate.
 Methods
 Three hundred patients with primary operable invasive breast cancer had axillary ultrasound preoperatively. If the ultrasound was normal the patient was offered a sentinel node procedure. If it identified equivocal nodes a fine needle cytology was performed. If the cytology was benign a sentinel node biopsy was performed. If the cytology was malignant then an axillary node clearance was performed. In cases where pathological nodes were identified on imaging, cytology was performed to confirm malignancy. An axillary node clearance was then performed.
 Results.
 Eighty three percent of our patients (n=249) had a normal axillary ultrasound pre-operatively. Of these 74.5% had a benign sentinel node biopsy. Sixty two percent of patients with equivocal nodes on pre-operative imaging had metastases on final histology (n=19). Of these 63% (n=12) were correctly identified pre-operatively with fine needle aspirate cytology of the equivocal node and had an axillary node clearance performed form the outset. Ultrasound identified pathological nodes in 7% of our patients (n=20). Malignancy was confirmed on cytology and an axillary node clearance was performed.
 Using ultrasound and fine needle aspirate cytology to assess the axilla pre-operatively sentinel node biopsy was performed in 265 patients (88%). Of these, 74.8% had a benign final histology. Thirty two patients had a pre-operative diagnosis of nodal metastases and had an axillary node clearance. All 32 had lymph node metastases on final histology. Factors that predicted for a malignant sentinel node were lymphovascular invasion (p<0.001), tumour grade (p<0.008) and size of tumour (p<0.001).
 Conclusion
 Eighty eight percent of our patients had a sentinel lymph node biopsy to stage the axilla. Pre-operative ultrasound combined with cytology correctly determined the status of the node in 78% of cases. Our rate of second axillary operations was reduced by 32%. Importantly all patients diagnosed with node metastases pre-operatively and advised to have an axillary node clearance did have metastases on final histology. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1019.
#5045 Background: The factors leading to breast cancer recurrence are incompletely understood. We carried out a retrospective study of outcome for 1065 breast cancer patients for which we examined factors correlating with cancer recurrence. We found that infection of wounds after surgery for primary disease positively correlated with cancer recurrence (Murthy et al, BJC 2007). Patients with wound complications were 3 fold more likely to have systemic recurrences than those without (p<0.0001). The aim of our study is to determine mechanisms responsible for this correlation. Our approach is based on two possible theories. First, patients may have an underlying immune dysfunction that predisposes them to developing both wound complications and also recurrence. Secondly, factors released at sites of wound complications may have direct influences on the remaining occult tumour cells, thereby increasing the likelihood of metastases.
 Methods: Patients with primary operable breast cancer were recruited prospectively. Blood was collected from patients pre-operatively, 4 and 16h post-operatively and again at 2 weeks, 3 and 6 months post-operatively. A variety of investigations were carried out on each sample to establish the immune status of the patient at that time point, and to identify potential mediators of cross talk between the immune system, the wound and any occult tumour cells. These investigations include: a) Full blood count; b) Immune cell phenotyping (absolute numbers/frequency of B, T lymphocytes and Natural Killer (NK) cell sub-types using multi-colour flow-cytometry); c) Cytokine profiling (using fluid phase cytometric multiplex immunoassays for 27 critical cytokines). Patients were followed up post-operatively for wound complications.
 Results:
 In our cohort of 57 patients, those who underwent a mastectomy were four times more likely to develop a post-operative wound infection than those who had breast conserving surgery (p=0.022). There was no significant difference in pre-operative absolute numbers of B and T lymphocytes or NK cells between the two groups. The percentage drop in absolute numbers of NK cells at 4 hours post-operatively was greater in the mastectomy group than in patients having breast conserving surgery (p=0.008). Mastectomy patients also dropped their CD45 counts by a significantly greater percentage (p=0.024). No significant difference was noted in the CD3, CD4, CD8 and CD19 counts between the two groups. Patients who developed wound infections showed peaks in levels of either Interleukin 5 or Interleukin 6.
 Conclusion
 Disruption of immune mechanisms as a result of increased surgical stresses in mastectomy patients contributes to a higher rate of wound complications. This may also provide a window of opportunity for the dissemination of tumour cells with their latent potential for reactivation and the development of metastases. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5045.
Introduction:Ultrasound combined with fine needle aspiration cytology is effective in pre-operative staging of the axilla in breast cancer. Accurate pre-operative diagnosis of lymph node metastases allows for a one stage axillary operation and may also influence decisions regarding neo-adjuvant chemotherapy and breast reconstruction. The aim of this study is to identify pathological and patient factors that influence the accuracy of ultrasound and FNAC in determining the status of the axilla pre-operatively.Methods:Three hundred patients with primary operable invasive breast cancer had an axillary ultrasound pre-operatively. If the ultrasound was normal the patient was offered a sentinel node biopsy. If it identified equivocal or pathological nodes a fine needle aspirate cytology was performed. If the cytology was malignant then an axillary node clearance was performed.Results:Ultrasound combined with FNAC correctly determined the status of the axilla pre-operatively in 78% of cases. Sensitivity for the detection of metastases was 32% with 100% specificity. Factors affecting the accuracy of ultrasound and FNAC were the pathological size of tumour (p<0.05) and the size of the metastases (p<0.05). Age of the patient, pathological grade and type of tumour did not significantly affect the accuracy of the procedure.Conclusion:Ultrasound combined with fine needle aspirate cytology can be used effectively to determine the status of the axilla pre-operatively. All patients regardless of age or their particular tumour characteristics should be offered this procedure pre-operatively. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5020.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.