Clinical response to primary letrozole therapy in elderly patients with early breast cancer : possible role for p53 as a biomarker

Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70–101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI – 34–72) and the median time to progression was 43 months (95% CI – 22–64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival (p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group

Feasibility of Use of a Barbed Suture (V-Loc 180) for Quilting the Donor Site in Latissimus Dorsi Myocutaneous Flap Breast Reconstruction

BackgroundLatissimus dorsi (LD) myocutaneous flap is a popular method of breast reconstruction which can be associated with high incidence of seroma formation. Quilting sutures at the harvest site are used to reduce this. Barbed sutures are self anchoring sutures which avoid multiple knotting and can be useful in quilting.MethodsA retrospective analysis of prospectively maintained database of patients who underwent LD flap breast reconstruction between January 2009 and January 2011 was carried out. Seroma formation at the harvest site, wound related complications, inpatient stay and duration of surgery were analysed and a comparison was made between two groups where quilting was done with barbed (V-Loc) suture and conventional polydioxanone (PDS) II sutures.ResultsFifty-seven patients were included of which 33 had quilting by V-Loc sutures and in 24 patients PDS II suture was used. Median age in the PDS group was 55 years (interquartile range [IQR)], 45 to 61 years) which was comparable to the V-Loc group (53 years [IQR, 48 to 59 years]; P-value 0.948). Sixteen patients (28%) had significant seroma formation and 5 (9%) patients developed superficial wound dehiscence. Incidences of seroma or wound complications were comparable (P-value 0.378 and 1.00, respectively). Secondary outcomes such as total duration of surgery, total inpatient stay, total amount of drain at the donor site were also similar in two groups.ConclusionsUse of barbed sutures for quilting the donor site in LD flap reconstruction is a feasible option and the associated seroma formation and wound complications are comparable with conventional sutures

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Bayesian risk maps for Schistosoma mansoni and hookworm mono-infections in a setting where both parasites co-exist

There is growing interest in the use of Bayesian geostatistical models for predicting the spatial distribution of parasitic infections, including hookworm, Schistosoma mansoni and co-infections with both parasites. The aim of this study was to predict the spatial distribution of mono-infections with either hookworm or S. mansoni in a setting where both parasites co-exist. School-based cross-sectional parasitological and questionnaire surveys were carried out in 57 rural schools in the Man region, western Côte d’Ivoire. A single stool specimen was obtained from each schoolchild attending grades 3-5. Stool specimens were processed by the Kato-Katz technique and an ether concentration method and examined for the presence of hookworm and S. mansoni eggs. The combined results from the two diagnostic approaches were considered for the infection status of each child. Demographic data (i.e. age and sex) were obtained from readily available school registries. Each child’s socio-economic status was estimated, using the questionnaire data following a household-based asset approach. Environmental data were extracted from satellite imagery. The different data sources were incorporated into a geographical information system. Finally, a Bayesian spatial multinomial regression model was constructed and the spatial patterns of S. mansoni and hookworm mono-infections were investigated using Bayesian kriging. Our approach facilitated the production of smooth risk maps for hookworm and S. mansoni mono-infections that can be utilized for targeting control interventions. We argue that in settings where S. mansoni and hookworm co-exist and control efforts are under way, there is a need for both mono- and co-infection risk maps to enhance the cost-effectiveness of control programmes

Bayesian risk maps for Schistosoma mansoni and hookworm mono-infections in a setting where both parasites co-exist

Abstract. There is growing interest in the use of Bayesian geostatistical models for predicting the spatial distribution of parasitic infections, including hookworm, Schistosoma mansoni and co-infections with both parasites. The aim of this study was to predict the spatial distribution of mono-infections with either hookworm or S. mansoni in a setting where both parasites co-exist. School-based cross-sectional parasitological and questionnaire surveys were carried out in 57 rural schools in the Man region, western Côte d’Ivoire. A single stool specimen was obtained from each schoolchild attending grades 3-5. Stool specimens were processed by the Kato-Katz technique and an ether concentration method and examined for the presence of hookworm and S. mansoni eggs. The combined results from the two diagnostic approaches were considered for the infection status of each child. Demographic data (i.e. age and sex) were obtained from readily available school registries. Each child’s socio-economic status was estimated, using the questionnaire data following a household-based asset approach. Environmental data were extracted from satellite imagery. The different data sources were incorporated into a geographical information system. Finally, a Bayesian spatial multinomial regression model was constructed and the spatial patterns of S. mansoni and hookworm mono-infections were investigated using Bayesian kriging. Our approach facilitated the production of smooth risk maps for hookworm and S. mansoni mono-infections that can be utilized for targeting control interventions. We argue that in settings where S. mansoni and hookworm co-exist and control efforts are under way, there is a need for both mono- and co-infection risk map

A Bayesian approach to estimate the age-specific prevalence of Schistosoma mansoni and implications for schistosomiasis control

Models that accurately estimate the age-specific infection prevalence of Schistosoma mansoni can be useful for schistosomiasis control programmes, particularly with regard to whether mass drug administration or selected treatment should be employed. We developed a Bayesian formulation of an immigration-death model that has been previously proposed, which used maximum likelihood inference for estimating the age-specific S. mansoni prevalence in a dataset from Egypt. For comparative purposes, we first applied the Bayesian formulation of the immigration-death model to the dataset from Egypt. We further analysed data obtained from a cross-sectional parasitological survey that determined the infection prevalence of S. mansoni among 447 individuals in a village in Côte d’Ivoire. Three consecutive stool samples were collected from each participant and analysed by the Kato-Katz technique. In the Côte d’Ivoire study, the observed S. mansoni infection prevalence was 41.6% and varied with age. The immigration-death model was able to correctly predict 50% of the observed age group-specific point prevalences. The model presented here can be utilized to estimate S. mansoni community infection prevalences, which in turn helps in the strategic planning of schistosomiasis control