The influence of age, comorbidity and frailty on treatment with surgery and systemic therapy in older women with operable triple negative breast cancer (TNBC) in England: A population-based cohort study.

BACKGROUND: Surgery and chemotherapy use were studied among older women with early stage triple negative breast cancer (TNBC) in a population-based cohort. METHODS: Women aged ≥50 years with unilateral early (stage 1-3a) TNBC diagnosed in 2014-2017 were identified from English cancer registration data. Information on surgery and chemotherapy was from linked Hospital Episode Statistics and Systemic Anti-Cancer Therapy datasets, respectively. Logistic regression was used to investigate the influences of patient age, comorbidity and frailty on uptake of surgery and chemotherapy. RESULTS: There were 7094 women with early stage TNBC. Overall rate of surgery was 94%, which only decreased among women aged ≥85 years (74%) and among the most frail. Among the 6681 women receiving surgery, 16% had neoadjuvant and 42% had adjuvant chemotherapy; the use of both decreased with age. More comorbidities and greater frailty were associated with lower rates of chemotherapy. There were differences in the uptake of chemotherapy across geographical regions and in the neoadjuvant and adjuvant chemotherapy regimens between age groups. CONCLUSION: Majority of older women with early TNBC had surgery, although some physically fit older women did not. Chemotherapy use varied by age and fitness.

Do surgical margins matter after mastectomy? A systematic review.

BACKGROUND: No consensus exists regarding adequacy of margins after mastectomy. To determine if pathological margin proximity is associated with local (LR) or distant recurrence after mastectomy for early invasive breast cancer or ductal carcinoma in situ. METHODS: A systematic review of literature published from 1980 to 2019 and meta-analysis was conducted. Unpublished data were sought from authors (PROSPERO (CRD42019127541)). Thirty-four studies comprising 34,833 breast cancer patients were included in the quantitative synthesis. Eligible studies reported on patients undergoing curative mastectomy for cancer allowing estimation of outcomes in relation to margin status/width. The association between pathological margin status and local (LR) and distant recurrence was considered using random effects modelling. PRISMA guidelines were followed. RESULTS: Positive margins were associated with increased LR on multivariable analyses (HR, 2·64, (95%CI 2·01-3·46)) and LR was higher regardless of the distance of tumour from the margin defined as positive. After skin-sparing mastectomy, positive margins were associated with increased LR (HR 3·40, (95%CI 1·9-6·2)). In the 4 studies reporting distant recurrence, patients with involved margins had a higher risk (HR 1·53, (95%CI 1·03-2·25)). CONCLUSIONS: Failure to achieve clear margins after mastectomy may increase the risks of local and distant recurrence. Adequate margin clearance should be recommended to minimize recurrence after mastectomy in National and International Guidelines.

Construction of the secondary care administrative records frailty (SCARF) index and validation on older women with operable invasive breast cancer in England and Wales: a cohort study.

OBJECTIVES: Studies that use national datasets to evaluate the management of older women with breast cancer are often constrained by a lack of information on patient fitness. This study constructed a frailty index for use with secondary care administrative records and evaluated its ability to improve models of treatment patterns and overall survival in women with breast cancer. DESIGN: Retrospective cohort study. PARTICIPANTS: Women aged ≥50 years with oestrogen receptor (ER) positive early invasive breast cancer diagnosed between 2014 and 2017 in England. METHODS: The secondary care administrative records frailty (SCARF) index was based on the cumulative deficit model of frailty, using International Statistical Classification of Diseases, Injuries and Causes of Death, 10th revision codes to define a set of deficits. The index was applied to administrative records that were linked to national cancer registry datasets. The ability of the SCARF index to improve the performance of regression models to explain observed variation in the rate of surgery and overall survival was evaluated using Harrell's c-statistic and decision curve analysis. External validation was performed on a dataset of similar women diagnosed in Wales. RESULTS: The SCARF index captured 32 deficits that cover functional impairment, geriatric syndromes, problems with nutrition, cognition and mood, and medical comorbidities. In the English dataset (n=67 925), the prevalence of frailty in women aged 50-69, 70-79 and ≥80 years was 15%, 28% and 47%, respectively. Adding a frailty measure to regression models containing age, tumour characteristics and comorbidity improved their ability to: (1) discriminate between whether a woman was likely to have surgery and (2) predict overall survival. Similar results were obtained when the models were applied to the Welsh cohort (n=4 230). CONCLUSION: The SCARF index provides a simple and consistent method to identify frailty in population level data and could help describe differences in breast cancer treatments and outcomes.

Initiation of adjuvant chemotherapy and trastuzumab for human epidermal growth receptor 2-positive early invasive breast cancer in a population-based cohort study of older women in England.

BACKGROUND: Clinical guidance on recommended treatment for older patients with breast cancer is often ambiguous, particularly in the context of comorbidities and poor functional status. Older patients, aged 70 years and over, account for a substantial proportion of women with breast cancer yet are underrepresented in randomized controlled trials. This paper investigates the initiation of adjuvant chemotherapy and trastuzumab in older patients in routine care. MATERIALS AND METHODS: Women, aged 50 years and over, newly diagnosed with human epidermal growth receptor 2 (HER2)-positive early invasive breast cancer from January 2014 to December 2017 were identified from the England Cancer Registry. Chemotherapy and trastuzumab use was obtained from the Systemic Anti-Cancer Therapy (SACT) dataset. Patient and tumor characteristics influential in treatment decision-making were included in multilevel mixed-effects logistic regression models. RESULTS: 10% of women had HER2-positive tumors. Initiation of adjuvant chemotherapy and trastuzumab decreased with age from ≥70% among women aged 50-64 years to <15% among women aged 80+ years. Initiation varied additionally by tumor characteristics and number of comorbidities. Age remained a factor in treatment decisions despite favorable other factors, with lower use among women aged 70+ years. There was also marked variation across geographical regions. CONCLUSIONS: In women with operable HER2-positive early invasive breast cancer, adjuvant chemotherapy plus trastuzumab was started less frequently as age increased, regardless of tumor characteristics or comorbidity burden. There was substantial variation in the proportion of women who started these treatments across the country.

Addressing frailty in patients with breast cancer: A review of the literature.

Various studies have documented variation in the management of older patients with breast cancer, and some of this variation stems from different approaches to balancing the expected benefit of different treatments, with the ability of patients to tolerate them. Frailty is an emerging concept that can help to make clinical decisions for older patients more consistent, not least by providing a measure of 'biological' ageing. This would reduce reliance on 'chronological' age, which is not a reliable guide for decisions on the appropriate breast cancer care for older patients. This article examines the potential of frailty assessment to inform on breast cancer treatments. Overall, the current evidence highlights various benefits from implementing comprehensive geriatric assessment and screening for frailty in breast cancer patients. This includes a role in supporting the selection of appropriate therapies and improving physical fitness prior to treatment. However, there are challenges in implementing routine frailty assessments in a breast cancer service. Studies have used a diverse array of frailty assessment instruments, which hampers the generalisability of research findings. Consequently, a number of issues need to be addressed to clearly establish the optimal timing of frailty assessment and the role of geriatric medicine specialists in the breast cancer care pathway.

Surgery and adjuvant radiotherapy for unilateral ductal carcinoma in situ (DCIS) in women aged over 70 years: A population based cohort study.

BACKGROUND: There is little clinical evidence to guide treatment decisions for ductal carcinoma in situ (DCIS) in older women. This study evaluated how the management of DCIS in women aged 70 or more compared with women aged 50-69 in England and Wales. METHOD: The study identified women aged ≥50 years with new unilateral DCIS diagnosed between 2014 and 2016 from linked cancer registration and routine hospital datasets for England and Wales. Rates of surgery and adjuvant radiotherapy were examined by age, deprivation, fitness measures (comorbidity and frailty), method of presentation and tumour grade using multilevel logistic regression. RESULTS: 12,716 women were diagnosed with unilateral DCIS between 2014 and 2016, of whom 2,754 (22%) were aged ≥70 years and 74% were screen detected. High grade DCIS was common, irrespective of age and method of presentation. Fewer women aged ≥70 had surgery compared to women aged 50-69 (81% vs. 94%), which was only partly explained by poor fitness. Use of radiotherapy following breast conserving surgery was strongly associated with grade, and was received by less than 16% of all patients with low grade tumours. Over 70% of women aged 50-69 with high grade DCIS received radiotherapy, but this fell to 35% among women aged ≥80. Use of radiotherapy was not associated with patient fitness. CONCLUSION: Treatment decisions for women with DCIS varied by age at diagnosis. Lower rates of surgery and adjuvant radiotherapy in older women were only partly explained by patient fitness. Better evidence is needed to aid treatment selection for older women with DCIS.