The utility of the implementation science framework “Integrated Promoting Action on Research Implementation in Health Services” (i-PARIHS) and the facilitator role for introducing patient-reported outcome measures (PROMs) in a medical oncology outpatient department

Quality of Life Research - We evaluated the utility of the implementation science framework “Integrated Promoting Action on Research Implementation in Health Services” (i-PARIHS) for...     

Primary endocrine therapy as a treatment for older women with operable breast cancer – A comparison of randomised controlled trial and cohort study findings

Introduction: One third of all breast cancers occur in women over the age of 70. Primary endocrine therapy (PET) is used in some women to minimise morbidity in a population with higher rates of comorbidity and frailty. In the UK up to 40% of women over 70 are treated with PET although there is a high rate of variability of practice between centres reflecting a lack of guidance about case selection.     

Omission of surgery in older women with early breast cancer has an adverse impact on breast cancer‐specific survival

Background

Primary endocrine therapy is used as an alternative to surgery in up to 40 per cent of women with early breast cancer aged over 70 years in the UK. This study investigated the impact of surgery versus primary endocrine therapy on breast cancer‐specific survival (BCSS) in older women.

Methods

Cancer registration data for 2002–2010 were obtained from two English regions. A retrospective analysis was performed for women with oestrogen receptor (ER)‐positive disease, using statistical modelling to show the effect of treatment (surgery or primary endocrine therapy) and age and health status on BCSS. Missing data were handled using multiple imputation.

Results

Cancer registration data on 23 961 women were retrieved. After data preprocessing, 18 730 of 23 849 women (78·5 per cent) were identified as having ER‐positive disease; of these, 10 087 (53·9 per cent) had surgery and 8643 (46·1 per cent) had primary endocrine therapy. BCSS was worse in the primary endocrine therapy group than in the surgical group (5‐year BCSS rate 69·4 and 89·9 per cent respectively). This was true for all strata considered, although the difference was less in the cohort with the greatest degree of co‐morbidity. For older, frailer patients the hazard of breast cancer death had less relative impact on overall survival.

Conclusion

BCSS in older women with ER‐positive disease is worse if surgery is omitted. This treatment choice may contribute to inferior cancer outcomes. Selection for surgery on the basis of predicted life expectancy may permit choice of women for whom surgery confers little benefit.     

Factors affecting aminolaevulinic acid-induced generation of protoporphyrin IX.

Photodynamic therapy (PDT) may cause tumour cell destruction by direct toxicity or by inducing cellular hypoxia as a result of microcirculatory shutdown. Aminolaevulinic acid (ALA) causes cellular accumulation of protoporphyrin IX (PPIX) in cells exposed to it in excess. PPIX can be used as a photosensitizer for PDT. Microcirculatory shutdown may be induced by toxicity to the endothelial and vascular smooth muscle (VSM) cells or by release of vasoactive substances. We have studied whether PPIX is produced by endothelial, VSM and tumour cells on exposure to ALA and whether these cell lines are directly damaged by PDT in vitro. Tumour endothelial cells are angiogenic and we have, therefore, investigated the effect of cellular proliferation rates on PPIX generation. Tumour cells generate more PPIX intracellularly than the non-neoplastic cell lines studied and are correspondingly more sensitive to PDT-induced cytotoxicity. Endothelial cells are sensitive to PDT-induced cytotoxicity and accumulate between 1.5 and four times more PPIX when proliferating (as during tumour-induced angiogenesis) than when quiescent. We conclude that PPIX-mediated PDT may exert some of its effects on the microcirculation of treated tissues by direct toxicity to endothelial and VSM cells, and that this toxicity may be enhanced in the tumour microenvironment.     

Stage and treatment variation with age in postmenopausal women with breast cancer: compliance with guidelines

Breast cancer-specific mortality is static in older women despite having fallen in younger age groups, possibly due to lack of screening and differences in treatment. This study compared stage and treatment between two cohorts of postmenopausal women (55-69 vs >70 years) in a single cancer network over 6 months. A total of 378 patients were studied (>70: N=167, 55-69 years: N=210). Older women presented with more advanced disease (>70: metastatic/locally advanced 12%, 55-69 years: 3%, P<0.01). Those with operable cancer had a worse prognosis (Nottingham Prognostic Index (NPI) >70: median NPI 4.4, 55-69 years: 4.25, P<0.03). These stage differences were partially explained by higher screening rates in the younger cohort. Primary endocrine therapy was used in 42% of older patients compared with 3% in the younger group (P<0.001). Older women with cancers suitable for breast conservation were more likely to choose mastectomy (>70: 57.5% mastectomy rate vs 55-69 years: 20.6%, P<0.01). Nodal surgery was less frequent in older patients (>70: 6.7% no nodal surgery, 55-69 years: 0.5%, P<0.01) and was more likely to be inadequate (>70: 10.7% <4 nodes excised, 55-69 years: 3.4%, P<0.02). In summary, older women presented with more advanced breast cancer, than younger postmenopausal women and were treated less comprehensively.