Exploring variation in the clinical management and outcomes of older patients with early invasive breast cancer in England and Wales

Background: Around 55,000 new cases of breast cancer are diagnosed each year across the UK, making it the most common female cancer. Incidence is highest among the older population, with 24% of all new diagnoses comprising patients aged 75 and over. Treatment for breast cancer varies among individuals according to their demographics, tumour characteristics, health status and personal preferences. Age is an important influence on treatment decisions because increasing age is associated with the development of health conditions (comorbidities), but also because the biological changes which characterise the ageing process will vary between patients. Ideally, the overall health and fitness of each patient should be used to guide decision-making around breast cancer treatment. However, observational studies have reported a non-standardised approach to the management of breast cancer in older patients in the UK. This is compounded by a lack of high-quality evidence on the efficacy of breast cancer treatments among the older population. It is unclear whether observed treatment variation reflects appropriate modification of guideline recommendations to adjust for patient fitness, or whether treatment decisions are being based solely on chronological age. This aim of this PhD research is to examine how chronological age, comorbidity and frailty influence locoregional treatment decisions and survival outcomes among older women with early invasive breast cancer (EIBC) in NHS organisations in England and Wales.

Methods: An initial systematic review assessed how guideline adherence influences overall survival among women with EIBC with a particular focus on the evidence related to older patients. The findings informed the remaining four research objectives. The studies to answer these objectives used cancer registration records of women aged 50 and over diagnosed with EIBC between 2014 and 2019 in NHS organisations in England and Wales. The registration data were linked with other national datasets to obtain detailed information on routes to diagnosis, breast cancer treatment and survival outcomes. The first two research objectives focused on the impact of age, comorbidity burden and level of frailty on receipt of locoregional treatment for EIBC, as well as exploring the rates of regional and organisational variation in treatment. The final two studies explored whether survival outcomes among women with EIBC differed by type of locoregional treatment among women of different age groups, burden of comorbidity or level of frailty.

Results: The systematic review found that studies which typically reported better adherence to treatment guidelines found an association with improved overall survival among women with non-metastatic breast cancer. The evidence base had several weaknesses, including the lack of standardised definitions of guideline adherence. Adherence to treatment guidelines was worse among older women compared with their younger counterparts, but the evidence was inconsistent about whether improved survival among older women was associated with treatment guideline adherence. The impact of age, comorbidity and frailty on patterns of locoregional treatment, defined as breast surgery and post-mastectomy radiotherapy (PMRT), were explored, alongside regional variation in treatment rates. Older women with EIBC were more likely to be treated with a mastectomy, rather than with breast conserving surgery, compared with younger women. This was demonstrated to be regardless of tumour size, and could not be explained by differences in patient fitness. Rates of PMRT were not influenced by comorbidity or frailty, but decreased among women aged 80 and over. Substantial regional and organisational variation in treatment patterns for PMRT were seen among women with intermediate-risk EIBC, but not for women with high-risk EIBC. Survival probabilities were higher for patients who received breast conserving surgery with radiotherapy versus those who received a mastectomy with or without radiotherapy, and the difference in survival probabilities between the two treatments increased as age increased. No difference was seen for breast cancer specific survival. The association between post-mastectomy radiotherapy and survival did not differ by chronological age among women with high or intermediate-risk EIBC.

Conclusions: This research suggests that information on comorbidity and frailty are not being consistently incorporated into decision-making for locoregional treatment among older women with EIBC, and chronological age may be unduly influencing decisions about breast surgery and PMRT. The results of this research will help to inform decision-making for locoregional treatment by providing clinicians and patients with information on real-world decision making and outcomes among older women with EIBC in England and Wales.