Outcomes of complex oncoplastic breast surgery in older women. Analysis of data from the Age Gap cohort study.

KEY WORDS: Breast cancer, mastectomy, breast conserving surgery, post-mastectomy reconstruction, older women, quality of life.

Process evaluation of the Bridging the Age Gap in Breast Cancer decision support intervention cluster randomised trial.

BACKGROUND: The Bridging the Age Gap in Breast Cancer research programme sought to improve treatment decision-making for older women with breast cancer by developing and testing, in a cluster randomised trial (n = 1339 patients), two decision support interventions (DESIs). Both DESIs were used in the intervention arm and each comprised an online risk prediction model, brief decision aid and information booklet. One DESI supported the decision to have either primary endocrine therapy (PET) or surgery with adjuvant therapies and the second supported the decision to have adjuvant chemotherapy after surgery or not. METHODS: Sixteen sites were randomly selected to take part in the process evaluation. Multiple methods of data collection were used. Medical Research Council (MRC) guidelines for the evaluation of complex interventions were used. RESULTS: Eighty-two patients, mean age 75.5 (range 70-93), provided data for the process evaluation. Seventy-three interviews were completed with patients. Ten clinicians from six intervention sites took part in telephone interviews. Dose: Ninety-one members of staff in the intervention arm received intervention training. Reach: The online tool was accessed on 324 occasions by 27 clinicians. Reasons for non-use of the online tool were commonly that the patient had already made a decision or that there was no online access in the clinic. Of the 32 women for whom there were data available, fifteen from the intervention arm and six from the usual care arm were offered a choice of treatment. Fidelity: Clinicians used the online tool in different ways, with some using it during the consultation and others checking the online survival estimates before the consultation. Adaptation: There was evidence of adaptation when using the DESIs. A lack of infrastructure, e.g. internet access, was a barrier to the use of the online tool. The brief decision aid was rarely used. Mediators: Shared decision-making: Most patients felt able to contribute to decision-making and expressed high levels of satisfaction with the process. Participants' responses to intervention: Six patients reported the DESIs to be very useful, one somewhat useful and two moderately useful. CONCLUSIONS: Clinicians who participated were mainly supportive of the interventions and had attempted some adaptations to make the interventions applicable, but there were practical and engagement barriers that led to sub-optimal adoption in routine practice. TRIAL REGISTRATION: ISRCTN46099296 . Registered on 11 August 2016-retrospectively registered.

Observational cohort study in older women with early breast cancer: Use of radiation therapy and impact on health-related quality of life and mortality.

BACKGROUND: Radiotherapy reduces in-breast recurrence risk in early breast cancer (EBC) in older women. This benefit may be small and should be balanced against treatment effect and holistic patient assessment. This study described treatment patterns according to fitness and impact on health-related quality-of-life (HRQoL). METHODS: A multicentre, observational study of EBC patients aged ≥ 70 years, undergoing breast-conserving surgery (BCS) or mastectomy, was undertaken. Associations between radiotherapy use, surgery, clinico-pathological parameters, fitness based on geriatric parameters and treatment centre were determined. HRQoL was measured using the European Organisation for the Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: In 2013-2018 2811 women in 56 UK study centres underwent surgery with a median follow-up of 52 months. On multivariable analysis, age and tumour risk predicted radiotherapy use. Among healthier patients (based on geriatric assessments) with high-risk tumours, 534/613 (87.1%) having BCS and 185/341 (54.2%) having mastectomy received radiotherapy. In less fit individuals with low-risk tumours undergoing BCS, 149/207 (72.0%) received radiotherapy. Radiotherapy effects on HRQoL domains, including breast symptoms and fatigue were seen, resolving by 18 months. CONCLUSION: Radiotherapy use in EBC patients ≥ 70 years is affected by age and recurrence risk, whereas geriatric parameters have limited impact regardless of type of surgery. There was geographical variation in treatment, with some fit older women with high-risk tumours not receiving radiotherapy, and some older, low-risk, EBC patients receiving radiotherapy after BCS despite evidence of limited benefit. The impact on HRQoL is transient.

Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer.

BACKGROUND: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. METHODS: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. RESULTS: Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19-0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20-0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08-0.49];BCSS: HR 0.12 [95% CI 0.03-0.44]).Transient negative quality-of-life impacts were observed. CONCLUSIONS: Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. TRIAL REGISTRATION: ISRCTN 46099296.

Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life.

BACKGROUND: Age-related breast cancer treatment variance is widespread with many older women having primary endocrine therapy (PET), which may contribute to inferior survival and local control. This propensity-matched study determined if a subgroup of older women may safely be offered PET. METHODS: Multicentre, prospective, UK, observational cohort study with propensity-matched analysis to determine optimal allocation of surgery plus ET (S+ET) or PET in women aged ≥70 with breast cancer. Data on fitness, frailty, cancer stage, grade, biotype, treatment and quality of life were collected. Propensity-matching (based on age, health status and cancer stage) adjusted for allocation bias when comparing S+ET with PET. FINDINGS: A total of 3416 women (median age 77, range 69-102) were recruited from 56 breast units-2854 (88%) had ER+ breast cancer: 2354 had S+ET and 500 PET. Median follow-up was 52 months. Patients treated with PET were older and frailer than patients treated with S+ET. Unmatched overall survival was inferior in the PET group (hazard ratio, (HR) 0.27, 95% confidence interval (CI) 0.23-0.33, P < 0.001). Unmatched breast cancer-specific survival (BCSS) was also inferior in patients treated with PET (HR: 0.41, CI: 0.29-0.58, P < 0.001 for BCSS). In the matched analysis, PET was still associated with an inferior overall survival (HR = 0.72, 95% CI: 0.53-0.98, P = 0.04) but not BCSS (HR = 0.74, 95% CI: 0.40-1.37, P = 0.34) although at 4-5 years subtle divergence of the curves commenced in favor of surgery. Global health status diverged at certain time points between groups but over 24 months was similar when adjusted for baseline variance. INTERPRETATION: For the majority of older women with early ER+ breast cancer, surgery is oncologically superior to PET. In less fit, older women, with characteristics similar to the matched cohort of this study (median age 81 with higher comorbidity and functional impairment burdens, the BCSS survival differential disappears at least out to 4-5 year follow-up, suggesting that for those with less than 5-year predicted life-expectancy (>90 years or >85 with comorbidities or frailty) individualised decision making regarding PET versus S+ET may be appropriate and safe to offer. The Age Gap online decision tool may support this decision-making process (https://agegap.shef.ac.uk/). TRIAL REGISTRATION NUMBER: ISRCTN: 46099296.

Bridging the Age Gap in breast cancer: Impact of chemotherapy on quality of life in older women with early breast cancer.

INTRODUCTION: Older patients with early breast cancer (EBC) derive modest survival benefit from chemotherapy but have increased toxicity risk. Data on the impact of chemotherapy for EBC on quality of life in older patients are limited, but this is a key determinant of treatment acceptance. We aimed to investigate its effect on quality of life in older patients enrolled in the Bridging the Age Gap study. MATERIALS AND METHODS: A prospective, multicentre, observational study of EBC patients ≥70 years old was conducted in 2013-2018 at 56 UK hospitals. Demographics, patient, tumour characteristics, treatments and adverse events were recorded. Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires (EORTC-QLQ) C30, BR23 and ELD 15 plus the Euroqol-5D (eq-5d) over 24 months and analysed at each time point using baseline adjusted linear regression analysis and propensity score-matching. RESULTS: Three thousand and four hundred sixteen patients were enrolled in the study; 1520 patients undergoing surgery and who had high-risk EBC were included in this analysis. 376/1520 (24.7%) received chemotherapy. At 6 months, chemotherapy had a significant negative impact in several EORTC-QLQ-C30 domains, including global health score, physical, role, social functioning, cognition, fatigue, nausea/vomiting, dyspnoea, appetite loss, diarrhoea and constipation. Similar trends were documented on other scales (EORTC-QLQ-BR23, EORTC-QLQ-ELD15 and EQ-5D-5L). Its impact was no longer significant at 18-24 months in unmatched and matched cohorts. CONCLUSIONS: The negative impact of chemotherapy on quality-of-life is clinically and statistically significant at 6 months but resolves by 18 months, which is crucial to inform decision-making for older patients contemplating chemotherapy. TRIAL REGISTRATION NUMBER ISRCTN: 46099296.

Treatment choices for older women with primary operable breast cancer and cognitive impairment: Results from a prospective, multicentre cohort study.

OBJECTIVES: The presence of dementia co-existing with a diagnosis of breast cancer may render management more challenging and have a substantial impact on oncological outcomes. The aim of this study was to examine the treatment and outcomes of older women with co-existing cognitive impairment and primary breast cancer. MATERIALS AND METHODS: A prospective, multicentre UK cohort study of women aged 70 years or over with primary operable breast cancer. Patients with and without cognitive impairment were compared to assess differences in treatment and survival outcomes. RESULTS: In total, 3416 women were recruited between 2013 and 2018. Of these, 478 (14%) had a diagnosis of dementia or cognitive impairment, subcategorised as mild, moderate and severely impaired. Up to 85% of women with normal cognition underwent surgery compared to 74%, 61% and 40% with mild, moderate, and severe impairment (p = 0.001). Among women at higher risk of recurrence, the uptake of chemotherapy was 25% for cognitively normal women compared to 20%, 22% and 12% for mild, moderate and severe impairment groups (p = 0.222). Radiotherapy use was similar in the subgroups. Although patients with cognitive impairment had shorter overall survival (HR: 2.10, 95% CI: 1.77-2.50, p < 0.001), there were no statistically significant differences in breast cancer specific or progression-free survival. CONCLUSION: Cognitive impairment appears to play a significant part in deciding how to treat older women with breast cancer. Standard treatment may be over-treatment for some women with severe dementia and careful consideration must be given to a more tailored approach in these women.

Bridging the age gap in breast cancer: evaluation of decision support interventions for older women with operable breast cancer: protocol for a cluster randomised controlled trial.

INTRODUCTION: While breast cancer outcomes are improving steadily in younger women due to advances in screening and improved therapies, there has been little change in outcomes among the older age group. It is inevitable that comorbidities/frailty rates are higher, which may increase the risks of some breast cancer treatments such as surgery and chemotherapy, many older women are healthy and may benefit from their use. Adjusting treatment regimens appropriately for age/comorbidity/frailty is variable and largely non-evidence based, specifically with regard to rates of surgery for operable oestrogen receptor-positive disease and rates of chemotherapy for high-risk disease. METHODS AND ANALYSIS: This multicentre, parallel group, pragmatic cluster randomised controlled trial (RCT) (2015-18) reported here is nested within a larger ongoing 'Age Gap Cohort Study' (2012-18RP-PG-1209-10071), aims to evaluate the effectiveness of a complex intervention of decision support interventions to assist in the treatment decision making for early breast cancer in older women. The interventions include two patient decision aids (primary endocrine therapy vs surgery/antioestrogen therapy and chemotherapy vs no chemotherapy) and a clinical treatment outcomes algorithm for clinicians. ETHICS AND DISSEMINATION: National and local ethics committee approval was obtained for all UK participating sites. Results from the trial will be submitted for publication in international peer-reviewed scientific journals. IRAS REFERENCE: 115550. TRIAL REGISTRATION NUMBER: European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2015-004220-61;Pre-results. Sponsor's Protocol Code Number Sheffield Teaching Hospitals STH17086. ISRCTN 32447*.

The information and decision support needs of older women (>75 yrs) facing treatment choices for breast cancer: a qualitative study.

OBJECTIVE: Primary Endocrine Therapy (PET) is a good alternative to surgery for breast cancer in older frailer women. Overall survival rates are equivalent although rates of local control are inferior. There is little research regarding the decision support needs of older patients faced with this choice. This qualitative study aimed to explore these among older breast cancer patients offered a choice of treatment, as the basis to develop an appropriate decision support tool. METHODS: Semi-structured interviews were undertaken with older women (>75 years) with breast cancer who had been offered a choice of PET or surgery at diagnosis. Women's involvement in their treatment decision and support for the process were explored and analysed using framework analysis. RESULTS: Thirty-three interviews were undertaken (median age 82, range 75-95 years, 22 PET, 11 surgery). Most women, regardless of treatment choice, wanted tailored information about the different treatment options, their impact on independence, the practicalities of treatment and the risk of recurrence and spread. Surgery was the treatment of choice in women wanting optimal disease control; those choosing PET felt that they were 'too old' for surgery and wanted minimal disruption. CONCLUSIONS: Older women described making active treatment decisions. However, some knowledge was inaccurate. Women wanted information and decision support from their clinicians along with a specific tailored information booklet to support this process.