IntroductionIn recent years, primary surgical treatment of older women with non-metastatic breast cancer has decreased in favor of primary endocrine therapy (PET). PET can be considered in women... Show moreIntroductionIn recent years, primary surgical treatment of older women with non-metastatic breast cancer has decreased in favor of primary endocrine therapy (PET). PET can be considered in women with a remaining life expectancy of less than five years. The aim of this study was to (1) assess the risk of distant metastases and other cause mortality over ten years in women aged 65 and older with stage I-III breast cancer treated with PET, (2) whether this was associated with geriatric characteristics and comorbidities and to (3) describe the reasons on which the choice for PET was made.MethodsWomen were included from the retrospective FOCUS cohort, which comprises all incident women diagnosed with breast cancer aged 65 or older between January 1997 and December 2004 in the Comprehensive Cancer Center Region West in the Netherlands. We selected women (N = 257) with stage I-III breast cancer and treated with PET from this cohort. Patient characteristics (including comorbidity, polypharmacy, walking, cognitive and sensory impairment), treatment and tumor characteristics were retrospectively extracted from charts. Outcomes were distant metastasis and other cause mortality. Cumulative incidences were calculated using the Cumulative Incidence for Competing Risks method (CICR); and subdistribution hazard ratios (SHR) were tested between groups based on age, geriatric characteristics and comorbidity with the Fine and Gray model.ResultsWomen treated with PET were on average 84 years old and 41% had one or more geriatric characteristics. Other cause mortality exceeded the cumulative incidence of distant metastasis over ten years (83 versus 5.6%). The risk of dying from another cause further increased in women with geriatric characteristics (SHR 2.06, p < 0.001) or two or more comorbidities (SHR 1.72, p < 0.001). Often the reason for omitting surgery was not recorded (52.9%), but if recorded surgery was omitted mainly at the patient's request (18.7%).DiscussionThis study shows that the cumulative incidence of distant metastasis is much lower than other cause mortality in older women with breast cancer treated with PET, especially in the presence of geriatric characteristics or comorbidities. This confirms the importance of assessment of geriatric characteristics to aid counseling of older women. Show less
Background: There is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and... Show moreBackground: There is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and apathy in older patients with breast cancer within the first 5 years after diagnosis.Methods: Women aged >= 70 years with early-stage breast cancer were included. Multivariate linear mixed models were used to assess longitudinal changes in symptoms of depression (according to the 15-item Geriatric Depression Scale), loneliness (according to the De Jong Gierveld Loneliness Scale) and apathy (according to the Starkstein Apathy Scale) over time at 3, 9, 15, 27 and 60 months follow-up.Results: In total, 299 patients were included (mean [standard deviation (SD)] age: 75.8 [5.2] years). At 3 months follow-up, shortly after the acute treatment, 10% of patients had sig-nificant depressive symptoms, while loneliness and apathy were present in 31% and 41% of all patients, respectively. Depression, loneliness and apathy scores showed no clinically relevant changes over time in the whole cohort. Patients who received adjuvant systemic therapies (i.e. endocrine therapy and/or chemotherapy and/or targeted therapy (trastuzumab)) had si-milar mental health outcomes as those who did not. However, frail patients had more symptoms (p < 0.001) and were more prone to develop depressive symptoms over time than non-frail patients (p = 0.002).Discussion: Depression, loneliness and apathy were frequently observed in older women with breast cancer and did not change over time. Patients who received adjuvant systemic therapies had similar mental health outcomes as those who did not. However, frail patients were at higher risk to experience these symptoms.(c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Lemij, A.A.; Liefers, G.J.; Derks, M.G.M.; Bastiaannet, E.; Fiocco, M.; Lans, T.E.; ... ; Glas, N.A. de 2023
Background A decline in physical activity and the ability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) could interfere with independent living and... Show moreBackground A decline in physical activity and the ability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) could interfere with independent living and quality of life in older patients, but may be prevented with tailored interventions. The aim of the current study was to assess changes in physical activity and ADL/IADL in the first 5 years after breast cancer diagnosis in a real-world cohort of older patients and to identify factors associated with physical decline. Methods Patients aged >= 70 years with in situ or stages I-III breast cancer were included in the prospective Climb Every Mountain cohort study. Linear mixed models were used to assess physical activity (according to Metabolic Equivalent of Task (MET) hours per week) and ADL/IADL (according to the Groningen Activity Restriction Scale (GARS)) over time. Secondly, the association with geriatric characteristics, treatment, quality of life, depression, apathy, and loneliness was analyzed. Results A total of 239 patients were included. Physical activity and ADL/IADL changed in the first 5 years after diagnosis (mean change from baseline -11.6 and +4.2, respectively). Geriatric characteristics at baseline were strongly associated with longitudinal change in physical activity and ADL/IADL, whereas breast cancer treatment was not. A better quality of life was associated with better physical activity and preservation of ADL/IADL, while depression and loneliness were negatively associated with these outcomes. Discussion Geriatric characteristics, loneliness, and depressive symptoms were associated with physical decline in older patients with breast cancer, while breast cancer treatment was not.A decline in physical activity and the ability to perform activities of daily living may interfere with quality of life in older patients. This article assessed changes in physical activity and activities of daily living in the first 5 years after breast cancer diagnosis in a real-world cohort of older patients and identified factors associated with physical decline. Show less
Introduction: Studies investigating the long-term effects of breast cancer treatment on cognition in older women with breast cancer are lacking, even though preserving cognition is highly valued by... Show moreIntroduction: Studies investigating the long-term effects of breast cancer treatment on cognition in older women with breast cancer are lacking, even though preserving cognition is highly valued by the older population. Specifically, concerns have been raised regarding the detrimental effects of endocrine therapy (ET) on cognition. Therefore, we investigated cogni-tive functioning over time and predictors for cognitive decline in older women treated for early breast cancer.Methods: We prospectively enrolled Dutch women aged >70 years with stage I-III breast can-cer in the observational CLIMB study. The Mini-Mental State Examination (MMSE) was performed before ET initiation and after 9, 15 and 27 months. Longitudinal MMSE scores were analysed and stratified for ET. Linear mixed models were used to identify possible pre-dictors of cognitive decline.Results: Among the 273 participants, the mean age was 76 years (standard deviation 5), and 48% received ET. The mean baseline MMSE score was 28.2 (standard deviation 1.9). Cogni-tion did not decline to clinically meaningful differences, irrespective of ET. MMSE scores of women with pre-treatment cognitive impairments slightly improved over time (significant interaction terms) in the entire cohort and in women receiving ET. High age, low educational level and impaired mobility were independently associated with declining MMSE scores over time, although the declines were not clinically meaningful.Conclusion: Cognition of older women with early breast cancer did not decline in the first two years after treatment initiation, irrespective of ET. Our findings suggest that the fear of declining cognition does not justify the de-escalation of breast cancer treatment in older women. 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Gans, E.A.; Portielje, J.E.A.; Dekkers, O.M.; Kroon, C.D.D.; Munster, B.C. van; Derks, M.G.M.; ... ; Bos, F. van den 2023
Introduction: Vulvar cancer is a disease that mainly affects older women. Frailty is an important predictor of outcomes and geriatric assessment can help tailor treatment decisions and improve... Show moreIntroduction: Vulvar cancer is a disease that mainly affects older women. Frailty is an important predictor of outcomes and geriatric assessment can help tailor treatment decisions and improve outcomes. This study aims to assess the prevalence of frailty in older women with vulvar cancer, and how it relates to integrated geriatric care and treatment according to the oncological guidelines. Materials and Methods: A single-center cohort study was performed, among patients 70 years and older, who were diagnosed with vulvar cancer at Leiden University Medical Center, between January 2012 and May 2020. Data on geriatric assessment, treatment decision-making and treatment-related outcomes were collected. Results: Our study included 114 patients. Mean age was 79.7 years, and 52 patients (45.6%) were frail. Of the frail patients, 42.0% were referred to a geriatrician. In eight of these cases, the geriatrician was actively involved in weighing the benefit and harm of standard oncological treatment versus de-escalated treatment. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with referral to a geriatrician and with active involvement of a geriatrician in decision making. In 26 of frail patients (50.0%) oncological treatment was de-escalated. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with de-escalation of treatment. De-escalated treatment did not compromise survival. Discussion: Frailty is prevalent among older women with vulvar cancer and is associated with referral to a geriatrician and de-escalation of oncological treatment. While this reflects that it is deemed important to tailor treatment decision for frail patients, most frail patients are not routinely evaluated by a geriatrician. Further multidisciplinary collaboration and research is necessary to optimize tailored treatment decisions for this patient group. Show less
Baltussen, J.C.; Glas, N.A. de; Liefers, G.J.; Slingerland, M.; Speetjens, F.M.; Bos, F. van den; ... ; Derks, M.G.M. 2023
New treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not... Show moreNew treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not included in pivotal trials. Therefore, we investigated treatment patterns and overall survival over time in older patients with metastatic colorectal cancer in a population-based study. We identified 22.192 Dutch patients aged & GE;70 years diagnosed with synchronous metastatic colorectal cancer between 2005 and 2020 from the Netherlands Cancer Registry. Changes in treatment over time were assessed with logistic regression models. Survival was assessed by Cox proportional hazard ratios (HR). Results showed that chemotherapy use increased between 2005 and 2015, but declined from 2015 onwards, while more patients received best supportive care. Over time, fewer patients underwent primary tumor resection alone. Although survival of both metastatic colon and rectal cancer improved until 2014, survival of colon cancer decreased from 2014 onwards (HR 1.04, 95% confidence interval [CI] 1.01-1.05), which was seen in all age groups. Survival of metastatic rectal cancer patients remained unchanged from 2014 onwards (HR 1.00, 95% CI 0.98-1.03) in all age groups. In conclusion, treatment patterns of Dutch older patients with synchronous metastatic colorectal cancer rapidly changed from 2005 to 2020, with increasing percentages of patients receiving best supportive care. Survival of metastatic colon cancer decreased from 2014 onwards. The implementation of a colorectal cancer screening program and patient selection might explain why only a subset of older patients seem to benefit from the availability of novel treatment options. Show less
Baltussen, J.C.; Glas, N.A. de; Liefers, G.J.; Slingerland, M.; Speetjens, F.M.; Bos, F. van den; ... ; Derks, M.G.M. 2023
New treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not... Show moreNew treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not included in pivotal trials. Therefore, we investigated treatment patterns and overall survival over time in older patients with metastatic colorectal cancer in a population-based study. We identified 22.192 Dutch patients aged ≥70 years diagnosed with synchronous metastatic colorectal cancer between 2005 and 2020 from the Netherlands Cancer Registry. Changes in treatment over time were assessed with logistic regression models. Survival was assessed by Cox proportional hazard ratios (HR). Results showed that chemotherapy use increased between 2005 and 2015, but declined from 2015 onwards, while more patients received best supportive care. Over time, fewer patients underwent primary tumor resection alone. Although survival of both metastatic colon and rectal cancer improved until 2014, survival of colon cancer decreased from 2014 onwards (HR 1.04, 95% confidence interval [CI] 1.01-1.05), which was seen in all age groups. Survival of metastatic rectal cancer patients remained unchanged from 2014 onwards (HR 1.00, 95% CI 0.98-1.03) in all age groups. In conclusion, treatment patterns of Dutch older patients with synchronous metastatic colorectal cancer rapidly changed from 2005 to 2020, with increasing percentages of patients receiving best supportive care. Survival of metastatic colon cancer decreased from 2014 onwards. The implementation of a colorectal cancer screening program and patient selection might explain why only a subset of older patients seem to benefit from the availability of novel treatment options. Show less
Background: Gene expression signatures have emerged to predict prognosis and guide the use of adjuvant therapy in patients with hormone receptor-positive breast cancer. The objective of this... Show moreBackground: Gene expression signatures have emerged to predict prognosis and guide the use of adjuvant therapy in patients with hormone receptor-positive breast cancer. The objective of this systematic review was to evaluate the prognostic and predictive value of commercially available gene expression signatures as a tool in adjuvant treatment decision-making in older patients with breast cancer.Methods: PubMed, MEDLINE, Embase, Web of Science, Cochrane Library, and Emcare were reviewed for relevant articles published before December 2021. Eligible studies were randomised trials and cohort studies that externally validated commercially available gene expression signatures in patients aged 65 years and older, including studies that presented subanalyses of this age group. Data extraction and risk of bias assessment was performed independently by two investigators.Results: Fifteen studies were included. Most studies investigated Oncotype DX, while results from other gene expression signatures were limited. Several studies underlined the prognostic performance of Oncotype DX and Prosigna Risk of Recurrence in older patients. Moreover, Oncotype DX was predictive for older patients with an intermediate-risk recurrence score; chemotherapy could be spared in both lymph node-positive and lymph node -negative disease.Conclusions: Prognostic performance has been demonstrated in older patients for several gene expression sig-natures. However, additional validation in patients with high-risk tumours is needed before gene expression signatures can be implemented in clinical practice as a prediction tool for adjuvant chemotherapy decision -making in the older age group. Show less
Ziel, D. van der; Derks, M.G.M.; Kapiteijn, E.; Bastiaannet, E.; Louwman, M.; Bos, F. van den; ... ; Glas, N.A. de 2022
Simple Summary Immunotherapy has strongly improved outcomes of patients with metastatic melanoma in recent years, but previous studies have shown that survival of older patients often lacks behind.... Show moreSimple Summary Immunotherapy has strongly improved outcomes of patients with metastatic melanoma in recent years, but previous studies have shown that survival of older patients often lacks behind. In this study, we investigated treatment prescription of immunotherapy over time in relation to age and survival. We showed that overall survival has improved in patients with synchronous metastasised melanoma aged <75 years, but not in patients aged 75 years or older. This might be explained by lower prescription rates of immunotherapy in this age group. Around 45% of patients with melanoma are older than 65 years. In recent years, immunotherapy has proven very effective for metastasised melanoma. The aim of this study was to investigate the time trends in treatment strategies and survival in older versus younger patients with synchronous metastasised melanoma. We included all patients diagnosed between 2000 and 2019 from the Netherlands cancer registry. We analysed changes in first-line systemic treatment using multivariable logistic regression models, stratified by age (<65, 65-75, and >= 75). Changes in overall survival were studied using multivariable Cox regression analysis. A total of 2967 patients were included. Immunotherapy prescription increased significantly over time for all age groups (<65 years: 11.8% to 64.9%, p < 0.001; 65-75 years: 0% to 68.6%, p < 0.001; >75 years: 0% to 39.5%, p < 0.001). In multivariable analyses, overall survival improved for patients aged <65 and 65-75 (HR 0.96, 95% CI 0.92-1.00 and HR 0.95, 95% CI 0.89-1.00, respectively), but not in patients over 75 (HR 0.98, 95% CI 0.91-1.05). In conclusion, overall survival has improved in patients with synchronous metastasised melanoma aged <75 years, but not in patients aged 75 years or older. This might be explained by lower prescription rates of immunotherapy in this age group. Show less
Purpose: Side effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation... Show morePurpose: Side effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL). Methods: Patients aged >= 70 years with stage I-III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time. Results: Overall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (b = - 4.37; 95% CI - 7.96 to - 0.78; p = 0.017) over the first 2 years, in particular on the future perspective subscale (b = - 11.10; 95% CI - 18.80 to - 3.40; p = 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement. Conclusion: A large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy. Show less
Introduction: Approximately 20% of older patients with breast cancer either present with metastatic disease or develop distant metastases after early breast cancer. The aims of this study were to... Show moreIntroduction: Approximately 20% of older patients with breast cancer either present with metastatic disease or develop distant metastases after early breast cancer. The aims of this study were to assess the prevalence of psychosocial problems in older patients with metastatic breast cancer, and to assess longitudinal changes in functional status, psychosocial functioning, and quality of life.Methods: For this prospective cohort study, patients with metastatic breast cancer aged 70 years and older were recruited in four Dutch hospitals. A baseline geriatric assessment was performed evaluating somatic, functional and psychosocial domains. Self-administered questionnaires were performed at baseline, three and six months: the Groningen Activity Restriction Scale, Geriatric Depression Scale. Loneliness scale, Apathy scale, Distress Thermometer and EORTC-QLQ-C30. Longitudinal changes on these scales were assessed by performing crude and adjusted linear mixed models.Results: Of the 100 patients that were included and underwent a geriatric assessment, 85 patients completed the baseline self-administered questionnaires. Almost half of the patients (46%) had depressive symptoms, and up to 64% experienced distress. Apathy was present in 53%, and 36% experienced loneliness. Three- and six-month questionnaires were completed by 77 and 72 patients, respectively. Although a significant increase in loneliness between baseline and six months was seen, this size of this change was not clinically relevant. No other longitudinal changes were found.Conclusion: The prevalence of distress, depressive symptoms, apathy and loneliness in older patients with metastatic breast cancer is high. Timely detection, for which a geriatric assessment is effective, could potentially improve quality of life. (C) 2020 The Authors. Published by Elsevier Ltd. Show less
As a result of our ageing population, breast cancer is becoming a disease of the elderly. Unfortunately, most studies investigating the efficacy of treatment do not include older patients and are... Show moreAs a result of our ageing population, breast cancer is becoming a disease of the elderly. Unfortunately, most studies investigating the efficacy of treatment do not include older patients and are not representative for the older population. In this thesis, we investigated whether there is variation in treatment and survival among older women with breast cancer in five European countries. Moreover, we study the long term efficacy of two types of adjuvant endocrine therapy in postmenopausal women. In addition, the effect of age and comorbidities on breast cancer death in the presence of competing mortality is studied. Finally, we investigate whether other endpoints in clinical studies might be more relevant for the older population and we introduce a new endpoint for clinical research in the older population with cancer. Show less
