Z. Rayter

An investigation into the relationship between salivary cortisol, stress, anxiety and depression.

This study examined the relationship between indices of self-reported emotional distress and absolute versus change in cortisol levels. Fifty-four women attending a diagnostic breast clinic completed scales measuring stress, anxiety and depression and provided five saliva samples over the course of a single day for the measurement of cortisol. No significant relationships were evident between absolute cortisol levels and the distress measures. Analysis of the change in cortisol levels revealed a non-linear interaction effect between stress and anxiety and time of day. There was a non-linear relation between time of day and cortisol levels, but the extent of the non-linearity was dependent upon levels of stress and anxiety, not depression. A relationship was apparent between indices of distress and change in cortisol levels, but not absolute levels of the hormone.

Factors affecting surgical margin clearance in screen-detected breast cancer and the effect of cavity biopsies on residual disease

One hundred and fourteen localization biopsies for screen-detected breast cancers were assessed for surgical margin clearance and presence of tumour in the cavity biopsies or subsequent resections. Inadequate surgical clearance (< or = 1 mm from the margin) in 88 patients was associated with high nuclear grade ductal carcinoma in situ, or extensive in-situ change accompanying invasive carcinomas, vs pure invasive carcinomas. Smaller localization biopsies (< or =50 g), larger tumours, and absence of a definite fine-needle aspiration cytological diagnosis of malignancy were also associated with inadequate excision. The radiographic characteristics of the tumours did not correlate with inadequate excision. Sixty-five patients had cavity biopsies taken at the time of surgery and 23 (35%) biopsies were positive, 20 of which were associated with incompletely excised tumours. Further excision in 78 patients yielded residual disease in 63%, most of whom had had inadequate surgical clearance. When cavity biopsies were taken with incompletely excised tumours, 15 of 88 subsequent resection specimens harboured residual disease compared with 29 of 88 without cavity biopsies. Although cavity biopsies increase the clearance margin, a negative cavity biopsy is not always an assurance of adequate excision.

Randomized clinical trial on the effect of fibrin sealant on latissimus dorsi donor‐site seroma formation after breast reconstruction

Latissimus dorsi (LD) flap procedures comprise 50 per cent of breast reconstructions in the UK. They are frequently complicated by seroma formation. Fibrin sealants may reduce seroma volumes at the donor site. The aim was to investigate the effect of fibrin sealant (Tisseel®) on total seroma volumes from the breast, axilla and back (donor site) after LD breast reconstruction. Secondary outcomes were specific back seroma volumes together with incidence and severity of wound complications.

Abstract P2-19-09: A multi-centre prospective phase - 2 surgical study evaluating health related quality of life after immediate latissimus dorsi (LD) breast reconstruction: Duration of effects over 2 years

Introduction: International decision-making bodies recommend integrating Patient Reported Outcome Measures (PROMs) alongside clinical outcomes. Methodology evaluating PROMs after types of breast reconstruction (BRR) has been poor in a systematic review of all studies since 19781. Few studies investigate the clinical meaning and magnitude of HRQL changes following types of immediate latissimus dorsi (LD) BRR (either implant-assisted (LDI) or tissue only autologous (ALD)) in relation to effective covariates: clinico-pathology, complications and adjuvant treatments. Twelve month data, showed poor role functioning and pain after ALD, with chemotherapy affecting all HRQL domains and no effects of radiotherapy (PMRT)2. Here we examined annual changes in each HRQL domain of a general cancer and breast cancer specific PROM and relationships with effective covariates over 36-months. Methods: An ethics approved multi centre prospective cohort study commenced in 2007. EORTC QLQ-C30, BR-23 and FACT-B were completed pre-operatively and at 3, 6, 12, 24 and 36 months post-operatively. Generalised estimating equations were used up to 24 months. The effect sizes (mean difference divided by the standard deviation) were assessed for all HRQL domains up to 36 months. Results: 142 patients were assessed (80 ALD, 62 LDI). The ALD group had a higher BMI (mean 27.6 versus 24.9 in LDI, p = 0.0025, effect size 3.04), more neo-adjuvant chemotherapy (12.5% versus 1.7% in LDI, p = 0.041) and symptomatic presentations (60% versus 45% in LDI, p = 0.047). Invasive tumours were significantly larger in the ALD (median 20, IQ range 14-30) compared to the LDI groups (median 15, IQ range 4.5-20.8) (p = 0.0031, effect size 2.99), with higher grade tumours (83% grades 2 and 3 for ALD, 70% for LDI) (p = 0.029), and lympho-vascular invasion (41% in ALD versus 21% in LDI, p = 0.019). The effects of explanatory variables on HRQL after 24 months were noticeably weaker compared to 12 months1. There were no significant differences between types of BRR regarding HRQL outcomes. PMRT adversely affected social functioning (p = 0.010, effect size = 2.6) and arm symptoms (p = 0.049, effect size = 1.97). Early complications ( Conclusion: Evaluation of HRQL effects particularly in functional domains (role and social) are important beyond 12 months up to 3 years, particularly following PMRT, early surgical complications and in younger women. The effects of PMRT may be a surrogate for more aggressive tumours affecting social functioning and arm symptoms. Disease-specific PROMS have a complimentary role alongside surgery-specific PROMS and require future analyses in cohort studies. 1. Winters ZE, et al. Annals of Surgery 2010; 252(6): 929-42. 2. Winters ZE, et al. BJS 2013; 100(2): 240-51. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-19-09.

Breast Screening in India: A UK Perspective on the Practicalities

This paper is offered as an Editorial, providing a UK perspective on discussions about the merits of a Breast Screening programme in India, based upon the UK and European experience.

P2-16-01: A Multi-Centre Prospective Cohort Study Evaluating Health Related Quality of Life after Types of Immediate Latissimus Dorsi (LD) Breast Reconstruction.

Introduction : Evidence for the clinical effectiveness of breast reconstruction based on Patient Reported Outcome Measures (PROMS) is lacking. Methodology evaluating PROMS after types of breast reconstruction has been poor with respect to study design, statistics, missing data and absence of prospective documentation of pre-defined complication data in a systematic review of all studies since 1978 1 . Furthermore, there is no reliable data on the effects of associated radiotherapy (RT) in this context. As a prelude to a proposed randomised trial in breast reconstruction, our aim was to conduct a ‘robust’ cohort study evaluating the effects of either implant-assisted LD (LDI) or tissue only (ALD) LD flap reconstruction in relation to key determinants including clinico-pathological parameters, complications and treatment schedules over a 36 month period. Methods : An MREC approved prospective longitudinal cohort study involving 6 centres commenced in early 2007. Serial PROMS using the EORTC QLQ-C30, BR-23, FACT-B, BIS and HADS, were completed pre-operatively and at 3, 6, 12, 24 and 36 months after surgery. Data up to 12 months were included in this analysis as data were sparse beyond this point; follow-up is ongoing. Demographic and clinical data were compared between the surgical groups. Generalised estimating equations were used to investigate demographic and clinical predictors of HRQL over time. Results : A total of 189 patients (107-ALD, 82-LDI) were recruited, with a mean age of 50 years (range 22–70). Baseline questionnaires were completed by 149 (79%) women, with 167 (88%) available at 12 months. Patients in the ALD group had a higher BMI (mean 27.3 versus 25.2 in LDI, p=0.001) and a greater likelihood of post-mastectomy RT (52% versus 30% in LDI, p=0.004). Only role functioning (p=0.001) and pain (p=0.003) were significantly adversely affected in the ALD v LDI group, with no statistically significant effects from PMRT on HRQL, although chemotherapy impaired global QoL (p Conclusion : There is increasing evidence of clinical equipoise between types of LD breast reconstruction and despite acknowledged cosmetic disadvantages the overall effects of PMRT on HRQL are minimal. The identification of important variables that may affect HRQL is crucial in all studies evaluating the effects of surgery on PROMS. Their integration into study results is essential for correct interpretation of clinically based assessments. This remains a challenging aspect in cohort studies, and emphasises the need for pragmatism in design of trials in the field. 1. Winters ZE, Benson JR, Pusic AL. Annals of Surgery 2010;252(6):929–42 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-01.

P3-07-23: Intraoperative Molecular Analysis of Sentinel Lymph Nodes in Breast Cancer Using One Step Nucleic Acid Amplification (OSNA).

Abstracts: Thirty-Fourth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 6‐10, 2011; San Antonio, TX Introduction: The OSNA method for the intra-operative analysis of sentinel lymph nodes (SLNs) in breast cancer has been introduced in 3 UK centres since 2007. The methodology uses a polymerase chain reaction to quantitate CK19, a cytokeratin specific to breast duct epithelial cells. OSNA provides “real-time” results on SLNs analysed as negative (−) or positive with either micro (+) or macrometastases (++). Method: This is a single-centre prospective pilot study of all patients undergoing breast cancer surgery including sentinel node biopsy from February 2010 to May 2011. SLN identification was performed using a dual localization technique with peri-areolar Patente V blue dye and Tc99 radio-active isotope. SLNs were cut into 4 slices labeled as A, B, C and D, respectively after the removal of all perinodal fat. In all SLNs, slices A and C were processed in OSNA and slices B and D underwent histological assessment by HE 23 mastectomies and 22 SLNB alone. The mean time for OSNA was 40.5, 51.8, 54 and 61.5 minutes for 1,2,3, and 4 sentinel lymph nodes respectively. Operation time was prolonged by a median of 20 minutes (range −48 to +65 minutes) WLEs were delayed by the greatest time Exclusions: Nodes that were not available for histological comparison i) nodes weighing <0.05g (n=34) were processed whole. ii) Departmental agreement from mid March 2011 to process nodes whole via OSNA (n=51); 6 had micro or macrometastases. Conclusion: OSNA prevented staged axillary surgery in 24 (21%) of patients. A median time of 20 minutes for the OSNA procedure is comparable with acceptable operating times. Current experience supports the use of OSNA for each individual whole SLN analysis. The pilot data has resulted in a prescribed change in policy to analyse the whole SLN using this technique. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-23.

Risk factors for psychological morbidity in women attending a one-stop diagnostic clinic with suspected breast disease

Abstract The present study was designed to identify risk factors for psychological morbidity in women attending a one-stop diagnostic clinic with suspected breast disease. A cohort of 158 women were recruited and were asked to complete scales measuring psychological morbidity and psychosocial factors in the period immediately before their appointment and to repeat the assessments of psychological morbidity on the day of the appointment. Relevant clinical and demographic data were also collated. Within the cohort 1.4% of respondents received a diagnosis of malignant disease. Psychological morbidity, both prior to and during the diagnostic appointment was strongly predicted by psychosocial factors (i.e., acceptance-resignation coping, personal self esteem and discrepancies in social support), accounting for 54% and 63% of the variance at pre-appointment and appointment day phases respectively. Other measured variables were found not to be correlated with and/or to account for a significant proportion of the variance in the measures of morbidity. These results suggest that these psychosocial variables should be targeted in interventions designed to reduce psychological morbidity in this patient group.