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The benefit of chemotherapy for older patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC) is a key area of debate. Gene expression profiling (GEP) may identify patients deriving benefit, but their predictive role has not been established for older adults. We summarise evidence on efficacy, safety, and quality-of-life impacts of chemotherapy and on GEP use and impact in older HR-positive, HER2-negative EBC patients. We conducted a literature search of PubMed and Embase on publications describing prospective studies evaluating chemotherapy in older adults with HR-positive, HER2-negative EBC and on publications describing retrospective and prospective studies evaluating GEP in older adults. Eight publications on chemotherapy use, including 2,035 older patients with EBC were selected. Only one trial evaluated chemotherapy survival benefits in older adults, showing no benefit. Of four studies comparing different regimens, only one showed the superiority of taxanes versus anthracyclines alone. Those investigating alternative regimens did not show improvements over standard regimens despite significant limitations. Five publications on GEP, including 445,323 older patients, were included and investigated Oncotype DX. Limited evidence shows that GEP aids treatment decisions in this population. GEP was offered less frequently to older versus younger patients. Higher Recurrence Score was prognostic for distant recurrence, but chemotherapy did not improve prognosis. In older patients with HR-positive, HER2-negative, chemotherapy survival benefits EBC are unclear and GEP is less used. Although its prognostic role is well established, its predictive role remains unknown. • Chemotherapy benefits in luminal early breast cancer patients ≥70 years are unclear. • Patients at higher recurrence risk may be identified with gene expression profiling. • However, whether this allows to predict chemotherapy benefits is unknown. • Chemotherapy here warrants shared decision-making beyond trial extrapolation. [ABSTRACT FROM AUTHOR]

Late recurrences are a key challenge for patients with early-stage oestrogen receptor-positive breast cancer, with the risk of disease relapse continuing steadily from 5 to more than 20 years after diagnosis. Five years of adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor was shown many years ago to improve survival. More recently, the trials of extended adjuvant endocrine therapy for more than 5 years have shown a further small gain, but with an associated small risk of increased long-term toxicity including bone loss, cardiovascular impairment and impaired quality of life. This review describes the efficacy and safety of extended endocrine therapy, the optimal selection criteria for patient benefit and the potential for novel agents to improve long-term outcomes. • Late recurrences are a key issue for patients with hormone receptor-positive early breast cancer. • Extended adjuvant endocrine therapy is associated with survival gains for patients at high-risk. • Long-term toxicities and impaired quality of life should be considered in decision-making. [ABSTRACT FROM AUTHOR]

• Radiotherapy use in older early-stage breast cancer patients is affected by age and relapse risk. • Despite geographical variation, geriatric parameters do not influence radiotherapy decisions. • Some fit older women with high-risk tumours do not receive radiotherapy. • Some older patients with low-risk cancer receive radiotherapy after breast-conserving surgery. • The impact of radiotherapy on quality-of-life is transient and mostly resolves by 18 months. 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). 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Breast cancer is increasingly prevalent in older adults and is a substantial part of routine oncology practice. However, management of breast cancer in this population is challenging because the disease is highly heterogeneous and there is insufficient evidence specific to older adults. Decision making should not be driven by age alone but should involve geriatric assessments plus careful consideration of life expectancy, competing risks of mortality, and patient preferences. A multidisciplinary taskforce, including members of the European Society of Breast Cancer Specialists and International Society of Geriatric Oncology, gathered to expand and update the previous 2012 evidence-based recommendations for the management of breast cancer in older individuals with the endorsement of the European Cancer Organisation. These guidelines were expanded to include chemotherapy toxicity prediction calculators, cultural and social considerations, surveillance imaging, genetic screening, gene expression profiles, neoadjuvant systemic treatment options, bone-modifying drugs, targeted therapies, and supportive care. Recommendations on geriatric assessment, ductal carcinoma in situ, screening, primary endocrine therapy, surgery, radiotherapy, adjuvant systemic therapy, and secondary breast cancer were updated. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. 46099296. • This is a multicentre, cohort study of 3416 women (aged >70 years) with breast cancer. • In older women with high-risk, early breast cancer, chemotherapy reduces quality of life. • The relevant affected domains include cognition, fatigue, physical, role and social functioning. • Chemotherapy QoL impacts are transient and largely resolve completely by 18–24 months. [ABSTRACT FROM AUTHOR]

Background: There are over half a million women with a previous breast cancer diagnosis living in the UK. It is important to establish their level of unmet physical and psychosocial needs, as many are not routinely seen for follow-up under current models of care.Methods: We conducted a retrospective analysis of early breast cancer survivors entering an Open Access Follow-Up (OAFU) programme in 2015. Unmet needs were assessed using the Holistic Needs Assessment (HNA) or extracted directly from the electronic patient record (EPR), when the HNA had not been completed.Results: Six hundred and twenty-five patients were eligible. Sixty-one per cent of the survivors had at least one unmet need and 18% had ⩾5 needs. Consistently higher levels of unmet needs were identified using the formal HNA checklist as opposed to extraction from EPR (P<0.001). Physical and emotional needs were the most frequently reported (55 and 24% respectively). Patients receiving endocrine therapy and those who had received chemotherapy were more likely to report unmet needs (both P<0.001).Conclusions: Unmet physical and emotional needs are common in breast cancer survivors. It is vital that the services are available for these patients as they transition from hospital-based follow-up to patient-led self-management models of care. [ABSTRACT FROM AUTHOR]

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population. [ABSTRACT FROM AUTHOR]

Simple Summary: People are more likely to develop cancer as they become older, and as people live longer, the number of older adults with cancer is steadily increasing. Managing cancer in older adults is challenging because they often have long-term conditions and wider needs that complicate treatment decisions and outcomes. However, the care of older adults with cancer is not formally taught during undergraduate medical education or postgraduate training in the United Kingdom. In this review, we provide an overview of the current education that medical students and training trainee doctors receive to prepare them for caring for older adults with cancer and highlight where challenges exist. We summarise the research conducted and strategies implemented internationally and use this knowledge to provide recommendations which may improve the education and training of doctors to meet the needs of older adults with cancer. Cancer is a disease associated with ageing. Managing cancer in older adults may prove challenging owing to pre-existing frailty, comorbidity, and wider holistic needs, as well as the unclear benefits and harms of standard treatment options. With the ongoing advances in oncology and the increasing complexity of treating older adults with cancer, the geriatric oncology field must be a priority for healthcare systems in education, research, and clinical practice. However, geriatric oncology is currently not formally taught in undergraduate education or postgraduate training programmes in the United Kingdom (UK). In this commentary, we outline the landscape of geriatric oncology undergraduate education and postgraduate training for UK doctors. We highlight current challenges and opportunities and provide practical recommendations for better preparing the medical workforce to meet the needs of the growing population of older adults with cancer. This includes key outcomes to be considered for inclusion within undergraduate and postgraduate curricula. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors are a new class of anticancer therapies that amplify T-cell-mediated immune responses against cancer cells. Immune checkpoint inhibitors have shown important benefits in phase 3 trials, and several agents have been approved for specific malignancies. Although adverse events from immune checkpoint inhibitors are a common occurrence, cardiotoxic effects are uncommon, but are often serious complications with a relatively high mortality. Most cardiotoxic effects appear to be inflammatory in nature. Clinical assessment of a combination of biomarkers, electrocardiography, cardiac imaging, and endomyocardial biopsy can be used to confirm a possible diagnosis. In this Review, we discuss the epidemiology of immune checkpoint inhibitor-mediated cardiotoxic effects, as well as their clinical presentation, subtypes, risk factors, pathophysiology, and clinical management, including the introduction of a new surveillance strategy. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common female cancer and the second cause of death among women worldwide. The 5-year relative survival rate recently improved up to 90% due to increased population coverage and women's attendance to organised mammography screening as well as to advances in therapies, especially systemic treatments. Screening attendance is associated with a mortality reduction of at least 30% and a 40% lower risk of advanced disease. The stage at diagnosis remains the strongest predictor of recurrences. Systemic treatments evolved dramatically over the last 20 years: aromatase inhibitors improved the treatment of early-stage luminal BC; targeted monoclonal antibodies changed the natural history of anti-human epidermal growth factor receptor 2-positive (HER2) disease; immunotherapy is currently investigated in patients with triple-negative BC; gene expression profiling is now used with the aim of personalising systemic treatments. In the era of precision medicine, it is a challenging task to define the relative contribution of early diagnosis by screening mammography and systemic treatments in determining BC survival. Estimated contributions before 2000 were 46% for screening and 54% for treatment advances and after 2000, 37% and 63%, respectively. A model showed that the 10-year recurrence rate would be 30% and 25% using respectively chemotherapy or novel treatments in the absence of screening, but would drop to 19% and 15% respectively if associated with mammography screening. Early detection per se has not a curative intent and systemic treatment has limited benefit on advanced stages. Both screening mammography and systemic therapies continue to positively contribute to BC prognosis. [ABSTRACT FROM AUTHOR]

probiotics and prebiotics can exert several beneficial effects in the gastrointestinal tract, such as anti-tumor activity; many studies have been conducted to analyze this activity and its mechanisms. However, their mode of action is not yet well understood. Recent data show the relationship between colon cancer and intestinal bacterial flora. We reviewed the evidence from, different studies in order to prove these beneficial effects on the host. [ABSTRACT FROM AUTHOR]