Questionnaires were administered to assess change in physical functioning in three age groups of patients with breast cancer: <60, 60–69, and ≥70 years. In all age groups, physical activity levels were significantly lower than prediagnostic levels at 1 and 2 years after diagnosis. Age >70 years was independently associated with decline in physical functioning between 1 and 2 years after diagnosis.
Keywords: Breast cancer, Aging, Physical activity, Treatment, Risk factors
Abstract
Background.
Previous retrospective studies have shown that physical functioning in older cancer survivors is affected after treatment, yet prospective data are lacking. The aim of this study was to assess change in physical functioning in different age groups of patients with hormone receptor-positive breast cancer who were enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase III trial.
Methods.
Two physical parameters were assessed. Physical functioning was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire 1 year (T1) and 2 years (T2) after diagnosis. Physical activity was measured in metabolic equivalent of task (MET) hours/week at T1 and T2. Physical activity before diagnosis (T0) was assessed retrospectively at the T1 questionnaire. Patients were divided into three age groups: <60, 60–69, and ≥70 years. Decline in physical functioning was assessed using linear regression analysis. Differences in mean values of physical activity levels were calculated using repeated-measures one-way analysis of variance.
Results.
A total of 431 patients were included for analysis. In all age groups, physical activity levels at T1 and T2 were significantly lower than prediagnostic physical activity levels (T0) (p < .001 for all age groups). Age ≥70 years was independently associated with decline in physical functioning between T1 and T2 (β = −4.62, 95% confidence interval −8.73 to −0.51, p = .028).
Conclusion.
Patients aged 70 years or older treated with breast surgery and adjuvant hormonal therapy did not improve between years 1 and 2 after diagnosis to the same extent as did younger patients.
Implications for Practice:
Although older patients constitute a large share of the breast cancer population, little is known about the effect and consequences of treatment of breast cancer in this specific age group. This study revealed that, unlike younger patients, older patients do not regain their physical abilities after surgical and adjuvant treatment for breast cancer. In older adults, the effect of treatment on physical functioning and independency could be more relevant than survival outcomes. Clinicians and older patients should be aware of the impact of treatment on physical functioning and prevent older patients from experiencing physical decline, which could lead to institutionalization and loss of independence. There is a need for age-specific guidelines that take into account the heterogeneity of the older population and for evidence-based treatment that focuses not only on cancer-specific outcomes but also on the consequences of treatment for physical and cognitive functioning and quality of life.
Introduction
Breast cancer is the most common diagnosed cancer among women and the second leading cause of cancer-related mortality in women in the U.S. [1]. Because of increasing life expectancy, breast cancer is becoming a disease of older adults. Of the estimated 246,660 new cases of breast cancer in the U.S. in 2016, 42.3% of the patients were 65 years or older [2].
Older patients comprise a heterogeneous group, with the majority having at least one comorbidity [3]. Multiple comorbidities can result in poorer functional status, quality of life, and health outcomes [4]. Furthermore, older patients with breast cancer are at increased risk for adverse events and toxicities of breast cancer treatment [5]. Consequently, older patients may be more vulnerable to decline of physical functioning during and after cancer treatment.
A recent meta-analysis has shown that physical activity has clinically important effects on physical function, psychological outcomes, and quality of life [6]. Functional limitations after breast cancer treatment are associated with higher all-cause mortality. Possibly, physical activity could modify these functional limitations [7]. In addition, a systematic review has shown that physical activity is associated with improved overall survival; however, it remains unclear whether this is a causal relation or an association that is explained by other factors [8]. In older adults, maintaining physical function could make the difference between independence and assisted living. Therefore, it is important to maintain the level of prediagnostic physical activity during and after breast cancer treatment in older patients.
Previous studies have shown that older cancer survivors are often affected in physical functioning, whereas younger patients are mostly affected in psychological functioning [9]. However, those studies were mostly retrospective in design and did not assess prediagnostic physical functioning. In addition, most of the studies had no information regarding comorbidities and treatment regimens, which may influence physical activity. The Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase III randomized controlled trial was originally designed to compare two endocrine therapies for early hormone receptor-positive breast cancer. Long-term exemestane alone was compared with tamoxifen followed by exemestane. In contrast to other trials, the TEAM trial had no upper age limit, so a relatively high number of older patients were included in the trial. The TEAM-Lifestyle (TEAM-L) side study provides extensive information on physical functioning before and 1 and 2 years after randomization. Because of its trial design, comorbidities and treatment strategies were well documented.
The aim of this study was to assess change in physical functioning in different age groups after surgical treatment among patients with hormone receptor-positive early-stage breast cancer.
Materials and Methods
The TEAM trial is a phase III, open-label, international randomized trial comparing 5 years of exemestane with 2.5–3 years of tamoxifen followed by 2.5–3 years of exemestane in patients with hormone receptor-positive early breast cancer. Details of the study design and population have been published previously [10]. The TEAM-L study is a side study from the TEAM trial. The population and study design of the TEAM-L study have been described in detail elsewhere [11]. Only patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were included, and there was no upper age limit.
In short, lifestyle and quality-of-life questionnaires were sent to Dutch participants of the TEAM trial to prospectively investigate lifestyle habits. One year after randomization, participants received a questionnaire on current (T1) and prediagnostic (T0) physical activity levels and on current quality-of-life indicators. Two years after randomization, a similar questionnaire was sent out.
Data Collection
Patient, tumor, and treatment characteristics were collected. Patients were included if physical functioning derived from the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire was available at T1 and T2. A previous study within the TEAM-L study did not observe differences in clinical characteristics between the population of the TEAM trial and the subgroup of TEAM-L respondents at T2 [11]. Patients were divided into three age groups: <60, 60–69, and ≥70 years.
Physical functioning was measured using two different questionnaires. First, self-reported physical functioning was assessed in the validated EORTC QLQ-C30 (version 3.0) at T1 and T2. The EORTC QLQ-C30 contained five items that were calculated into one physical functioning score as described previously [12].
Additionally, physical activity was quantified using the validated European Prospective Investigation into Cancer (EPIC) physical activity questionnaire [13]. In this questionnaire, patients were asked to report the amount of time they spent per week during summer and winter in recreational and household activities. Metabolic equivalent values were calculated from the mean hours reported to estimate the intensity of recreational and household activity per week (metabolic equivalent of task [MET] hours/week) [14].
Statistical Analysis
Statistical analysis was performed in SPSS version 20 and Stata 12.0. The TEAM lifestyle study was designed to assess change in functioning and quality of life in subgroups of patients. We used two-sided testing, and p values of ≤.05 were considered statistically significant. If a value of a specific characteristic of an individual patient was missing, it was assigned to the “unknown” category of that characteristic. The proportion of missing values for each characteristic is shown in Table 1 (unknown categories). For regression analysis, unknown categories in the characteristics were included as a separate category in the analysis (Table 2). Baseline characteristics among different age groups were compared using chi-square tests. Mean physical functioning scores derived from the EORTC questionnaire and mean MET hours/week in three age categories were calculated. Mean differences in physical functioning and physical activity between age groups were compared using one-way analysis of variance (ANOVA). Mean differences at the different time points within age groups were calculated by paired sample t test and repeated-measures one-way ANOVA. Change in physical functioning was calculated by subtracting the calculated score for physical functioning from the EORTC questionnaire at T2 by the calculated score at T1. Univariate and multivariable regression were used to estimate the change in physical functioning for several variables. In the multivariable regression analysis, we used an adjusted model, correcting for all known variables (age, number of comorbidities, body mass index [BMI], ECOG performance status, tumor stage, node stage, tumor grade, most extensive surgery, most extensive axillary surgery, radiotherapy, chemotherapy, and endocrine therapy).
Table 1.
Patient and treatment characteristics
Table 2.
Change in physical parameters from 1 to 2 years after diagnosis
Results
Patient Characteristics
Overall, 431 patients were included (Fig. 1). At baseline, BMI was higher in the older patients (p = .006). Patients in the oldest age group were more likely to present with stage II tumors (p = .010). In older patients, a mastectomy was performed more frequently in comparison with younger counterparts (p = .004). Additionally, older patients received radiotherapy and chemotherapy less often (p = .003 and p < .001 respectively). Older patients were more frequently assigned to the exemestane treatment arm (p = .008) (Table 1).
Figure 1.
Flowchart of the inclusion of patients in the TEAM-L study.
Abbreviations: T2, 2 years after diagnosis; TEAM, Tamoxifen Exemestane Adjuvant Multicenter; TEAM-L, Tamoxifen Exemestane Adjuvant Multicenter Lifestyle.
Physical Functioning
Physical functioning, expressed as a mean score within a range of 0–100, is reported only between T1 and T2 (no baseline results were available). As shown in Figure 2, physical functioning in the oldest age group was significantly lower than in the younger age groups at T1 and T2 (p < .001 for T1 and T2). Patients aged ≥70 years showed a mean (SE) decrease in physical functioning of −2.59 (1.46) points between T2 and T1, whereas patients aged less than 60 years showed an increase in physical functioning of 1.86 (0.95) points (p = .008). In addition, age ≥70 years was an independent predictor for decline in physical functioning in multivariable regression analysis compared with the youngest age group (β = −4.62; 95% confidence interval [CI], −8.73 to −0.51; p = .028) (Table 2).
Figure 2.
Mean physical functioning in different age groups. Mean physical functioning scores were calculated from the EORTC QLQ-C30 questionnaire.
Abbreviations: EORTC, European Organisation for Research and Treatment of Cancer; T1, 1 year after diagnosis; T2, 2 years after diagnosis.
Additional variables were tested for predictive value (Table 2). ECOG performance status of 1 was predictive for decrease in physical functioning in multivariable regression analysis (β = −3.65; 95% CI, −7.13 to −0.16; p = .040). Chemotherapy was a significant predictor for increased physical functioning in univariate analysis (β = 3.11; 95% CI, 0.68 to 5.55, p = .012) . In adjusted analysis, however, this effect was no longer significant (β = 0.40; 95% CI, −2.96 to 3.77; p = .813). A trend was found for decrease in physical functioning among patients who were assigned to the tamoxifen/exemestane treatment arm, even though younger patients were more likely to receive this combination (β = −2.08; 95% CI, −4.46 to 0.28; p = .084). After adjusted regression analysis, this effect increased (β = −2.44; 95% CI, −4.98 to 0.02; p = .052). The number of comorbidities was not predictive for physical functioning. No other tumor or treatment characteristics were predictive for change in physical functioning (Table 2).
Physical Activity
Mean values for physical activity measured in MET hours/week at T0, T1, and T2 are shown in Figure 3. Like the previous physical functioning score, mean physical activity was significantly lower in the oldest age group in comparison with the younger age groups (p < .001 at all time points). Patients in all age groups showed a strong decline in physical activity at T2 compared with T0 (p = .002 for age <60, p = .003 for age 60–69, p = .002 for age ≥70 years). Change in physical activity over time was not significantly different between age groups.
Figure 3.
Mean physical activity in different age groups. Mean physical activity was calculated from the EPIC physical activity questionnaire.
Abbreviations: EPIC, European Prospective Investigation into Cancer; T0, at time of diagnosis; T1, 1 year after diagnosis; T2, 2 years after diagnosis.
Age ≥70 years was not predictive for change in physical activity between T2 and T1 in univariate regression analysis compared with the youngest age group (β = −1.04; 95% CI, −4.32 to 2.24; p = 0.438) (Table 2). In addition, no other patient, tumor, or treatment characteristics were predictive for change in physical activity.
Discussion
This study has shown that patients aged 70 years or older treated with adjuvant hormonal therapy after breast cancer surgery showed a significantly stronger decline in physical functioning between 1 and 2 years after diagnosis compared with their younger counterparts. Furthermore, we observed a decrease in physical activity level 2 years after diagnosis compared with prediagnostic physical activity among postmenopausal patients with breast cancer.
Our findings are in line with previous studies that examined physical activity among patients with breast cancer and reported a strong decline in physical activity immediately after diagnosis [15–18]. Only one study has examined physical recovery after surgery. The authors retrospectively assessed physical activity measured in leisure MET hours/week before diagnosis, during treatment, and 1 year after diagnosis in a population-based cohort study among primary breast cancer patients aged 50–75 years. After an initial decrease in physical activity during treatment, physical activity increased toward prediagnostic value 1 year after surgery and age was associated with decrease in physical activity 1 year after surgery [16]. Although exact time points between the studies differ, there is a similar pattern of initial decrease followed by subsequent increase of physical activity among all patients with breast cancer. In addition, Cancer and Leukemia Group B (CALGB) 49907, a randomized controlled trial, and CALGB 369901, a prospective cohort study, assessed physical functioning among older women treated with chemotherapy. In both studies, physical functioning improved in the first 12 months. However, in line with our findings, patients experienced decline in physical functioning from 1 to 2 years after diagnosis [19, 20]. Figures 2 and 3 show a similar pattern for physical functioning and physical activity across age groups between 1 and 2 years after diagnosis, suggesting that there is a relation between the two parameters.
A possible explanation for the observed decline in physical functioning in the oldest patients may be that functional decline in older patients with breast cancer could be part of biological aging. This study had no control group of noncancer subjects with a similar age distribution, so we were unable to distinguish the impact of cancer and treatment on physical functioning from age-related deterioration. Two previous studies compared physical functioning in patients with cancer and a control group without cancer. Arndt et al. [21] compared physical functioning from the EORTC QLQ C-30 questionnaire of breast cancer patients 1 year after diagnosis with a control population. They found a difference in younger breast cancer patients, but not in older patients (70–80 years) [21]. Unfortunately, they did not report levels of physical functioning before diagnosis. Kroenke et al. [22] compared physical functioning in the Nurses’ Health Study before and after diagnosis. Functional decline among older women without breast cancer was half of that of older women with breast cancer [22]. They used a relatively young population, with a reported upper age limit of 72 years. In this breast cancer population, 68% used hormonal therapy and 20% used chemotherapy. Overall, functional decline in older patients with breast cancer is closely related to age. However, cancer and cancer therapy probably have impact on physical functioning, as is shown in the study by Kroenke et al. [22], and might accelerate decline in physical functioning.
Previous studies described a significant reduction in physical functioning during and after chemotherapy among patients with breast cancer [23–25]. In our study, there was an imbalance in the proportion of patients receiving adjuvant chemotherapy between the age groups, as 74% of the youngest patients received chemotherapy and none of the older patients received chemotherapy. This might affect the level of physical functioning as measured 1 year after diagnosis and change in functioning from 1 to 2 years after diagnosis. However, in the multivariable model in which chemotherapy was included as a covariate, older age remained an independent prognostic factor for physical decline. Furthermore, older patients were less frequently assigned to the tamoxifen treatment arm. This could be the result of randomization, but we cannot rule out that there is selective loss to follow-up among the older patients in the tamoxifen arm.
BMI was not predictive for change in physical functioning after surgery. This is an interesting finding, as BMI is associated with poor physical activity in patients with breast cancer [17]. We did observe a lower mean physical activity level among patients with obesity, although this level did not change significantly over time. Additionally, to our surprise, the number of comorbidities did not influence change in physical functioning. In contradiction to results in previous studies, patients with a higher number of comorbidities did not report lower mean levels of physical functioning [4, 23]. Probably this is because of the selection of patients in our study: only patients with a good ECOG performance status were included, resulting in lower numbers of comorbidities in the patient population compared with the general population [26]. As expected, higher ECOG performance status was predictive for decline in physical functioning independent of other patient characteristics. The performance status may therefore be a useful clinical tool to detect patients at risk for physical decline after breast cancer diagnosis. However, a previous study has shown that comprehensive geriatric assessment is a better predictor for physical functioning than the ECOG performance score in older patients [27]. In addition, geriatric assessment is able to identify areas of vulnerability that would not be identified by routine history and physical examination [28]. Because it is able to distinguish frail older patients from fit older patients, it is likely to be a better predictor than just chronological age for decline in physical functioning as well. Currently, the International Society for Geriatric Oncology advises that a geriatric assessment be performed in all older patients with cancer [29].
Although not statistically significant, there was a trend for decreased physical functioning among patients allocated to the tamoxifen/exemestane treatment arm. This could not be explained by adverse events: the TEAM trial found significantly more musculoskeletal adverse events, as they occurred more frequently in the exemestane treatment arm. No other adverse events associated with physical limitations were more frequently seen in the tamoxifen group [10].
The major strength of this study is the prospective design. We were able to prospectively collect reliable and well-registered data that made our study less subject to recall bias. Physical functioning was measured with two different validated questionnaires to increase the reliability of our findings. To our knowledge, this is the first study on physical functioning in older patients with breast cancer with a follow-up of 2 years. We thus provide further insight into recovery of physical functioning over the course of time. Furthermore, our study had no upper age limit, providing us with a unique opportunity to study older patients and examine the effect of age on physical activity and physical functioning.
However, this study was subject to several limitations as well. Most importantly, the TEAM trial included only patients with a low ECOG performance score. This led to inclusion of relatively fit older adults. Also, older patients included in the TEAM study had a high socioeconomic status and a low comorbidity burden in comparison with the age-matched general population [30]. Because of this selection, the effect of age on decline in physical functioning could be underestimated when findings are extrapolated to the general population. Furthermore, although postdiagnostic physical functioning and physical activity were examined prospectively, levels of physical activity before diagnosis were assessed retrospectively. Although the EPIC questionnaire is validated for prospective follow-up, it is not validated to assess physical activity retrospectively, and it could therefore be subject to recall bias. However, it is not likely that the effect of recall bias differed between age groups. In addition, no data on physical functioning before diagnosis was available, and therefore it is not possible to assess change from diagnosis to 1 year after diagnosis.
Physical parameters could be affected by recurrence of disease. In this study, the number of patients who experienced a recurrence was low (n = 9) and was divided equally among all age groups. Finally, we performed an additional analysis that showed that actual hours of activity corresponded well to physical activity calculated in MET hours.
It is important to prevent worsening of physical functioning in older patients, as it could interfere with independent living. This stresses the need for further research into the effect of intervention programs to prevent loss of functioning during hormonal treatment among older patients with breast cancer. A multitude of randomized controlled trials on the effect of exercise on quality of life in patients with cancer have been performed in the last decade. A recent meta-analysis evaluated exercise intervention among post-treatment cancer survivors. In the breast cancer subgroup analysis, researchers found an improvement in overall health-related quality of life at varying time points (12 weeks, 6 months). No sustainable effect of exercise on physical functioning was observed [31]. Unfortunately, this meta-analysis did not perform age-specific subgroup analyses. Most of the included trials focused on exercise interventions in younger patients and may not be suitable for older patients. Morey et al. [32] conducted a randomized controlled trial among older long-term cancer survivors (>65 years) examining the effect of a home-based tailored program promoting exercise and healthy diet. At 12 months of follow-up, they found an increase of physical functioning and overall quality of life in the intervention group compared with the control group [32]. This suggests that tailored exercise programs for older patients with breast cancer might be effective.
With regard to the expanding aging population, the increasing number of older patients with breast cancer, and continuously improving breast cancer treatments, more research is required to evaluate and improve long-term physical functioning in older patients with breast cancer. Unfortunately, older adults are generally underrepresented in clinical trials [33], and participating older patients are relatively healthy compared with the general population. Consequently, trial results cannot be extrapolated to the general older breast cancer population [30]. Furthermore, few studies investigate functional status and quality of life. These endpoints might be particularly relevant for older patients with breast cancer [34, 35]. Prospective studies that measure physical functioning before and after treatment are needed to evaluate change in physical functioning in relation to treatment.
Conclusion
Patients aged 70 years or older who were treated with breast surgery and adjuvant hormonal therapy did not improve in physical functioning between 1 and 2 years after diagnosis to the same extent as younger patients. With respect to our aging breast cancer population, more research is needed to clarify the interaction of physical functioning, breast cancer, and the aging process.
Acknowledgments
We thank the Datacenter Surgery of the Leiden University Medical Center for help with data management. The TEAM trial was funded by Pfizer Oncology. The TEAM-L study was funded by the Dutch Pink Ribbon Foundation (2008.WO01.C34).
Footnotes
For Further Reading: Trevor A. Jolly, Allison M. Deal, Kirsten A. Nyrop et al. Geriatric Assessment-Identified Deficits in Older Cancer Patients With Normal Performance Status. The Oncologist 2015;20:379–385.
Implications for Practice: The optimal evaluation to guide treatment decisions for older cancer patients is not known. The Karnofsky performance status (KPS) scale is frequently used to guide oncology practice, whereas the standard in geriatric medicine is the comprehensive geriatric assessment (GA). Comprehensive GA is time and resource intensive and impractical in routine cancer care. This study shows that a brief, mostly patient-administered GA can identify deficits that could affect treatment tolerance and outcomes in patients assessed as functionally normal by KPS. A brief GA should be incorporated into routine oncology practice for timely identification of patient deficits that may be remediable before or during treatment.
Author Contributions
Conception/Design: Marloes G.M. Derks, Nienke A. de Glas, Esther Bastiaannet
Data analysis and interpretation: Marloes G.M. Derks, Nienke A. de Glas, Esther Bastiaannet, Anton J.M. de Craen, Gerrit-Jan Liefers
Manuscript writing: Marloes G.M. Derks, Nienke A. de Glas, Esther Bastiaannet, Anton J.M. de Craen, Johanneke E.A. Portielje, Cornelis J.H. van de Velde, Floor E. van Leeuwen, Gerrit-Jan Liefers
Final approval of manuscript: Marloes G.M. Derks, Nienke A. de Glas, Esther Bastiaannet, Anton J.M. de Craen, Johanneke E.A. Portielje, Cornelis J.H. van de Velde, Floor E. van Leeuwen, Gerrit-Jan Liefers
Disclosures
The authors indicated no financial relationships.
References
- 1.DeSantis C, Ma J, Bryan L, et al. Breast cancer statistics, 2013. CA Cancer J Clin. 2014;64:52–62. doi: 10.3322/caac.21203. [DOI] [PubMed] [Google Scholar]
- 2.National Cancer Institute. SEER Stat Fact Sheets: Female Breast Cancer. Available at http://seer.cancer.gov/statfacts/html/breast.html. Accessed May 26, 2016.
- 3.Barnett K, Mercer SW, Norbury M, et al. Epidemiology of multimorbidity and implications for health care, research, and medical education: A cross-sectional study. Lancet. 2012;380:37–43. doi: 10.1016/S0140-6736(12)60240-2. [DOI] [PubMed] [Google Scholar]
- 4.Keating NL, Nørredam M, Landrum MB, et al. Physical and mental health status of older long-term cancer survivors. J Am Geriatr Soc. 2005;53:2145–2152. doi: 10.1111/j.1532-5415.2005.00507.x. [DOI] [PubMed] [Google Scholar]
- 5.van de Water W, Bastiaannet E, Hille ET, et al. Age-specific nonpersistence of endocrine therapy in postmenopausal patients diagnosed with hormone receptor-positive breast cancer: a TEAM study analysis. The Oncologist. 2012;17:55–63. doi: 10.1634/theoncologist.2011-0037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Fong DY, Ho JW, Hui BP, et al. Physical activity for cancer survivors: Meta-analysis of randomised controlled trials. BMJ. 2012;344:e70. doi: 10.1136/bmj.e70. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Braithwaite D, Satariano WA, Sternfeld B, et al. Long-term prognostic role of functional limitations among women with breast cancer. J Natl Cancer Inst. 2010;102:1468–1477. doi: 10.1093/jnci/djq344. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Fontein DB, de Glas NA, Duijm M, et al. Age and the effect of physical activity on breast cancer survival: A systematic review. Cancer Treat Rev. 2013;39:958–965. doi: 10.1016/j.ctrv.2013.03.008. [DOI] [PubMed] [Google Scholar]
- 9.Avis NE, Deimling GT. Cancer survivorship and aging. Cancer. 2008;113(suppl):3519–3529. doi: 10.1002/cncr.23941. [DOI] [PubMed] [Google Scholar]
- 10.van de Velde CJ, Rea D, Seynaeve C, et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): A randomised phase 3 trial. Lancet. 2011;377:321–331. doi: 10.1016/S0140-6736(10)62312-4. [DOI] [PubMed] [Google Scholar]
- 11.Voskuil DW, van Nes JG, Junggeburt JM, et al. Maintenance of physical activity and body weight in relation to subsequent quality of life in postmenopausal breast cancer patients. Ann Oncol. 2010;21:2094–2101. doi: 10.1093/annonc/mdq151. [DOI] [PubMed] [Google Scholar]
- 12.Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–376. doi: 10.1093/jnci/85.5.365. [DOI] [PubMed] [Google Scholar]
- 13.Cust AE, Smith BJ, Chau J, et al. Validity and repeatability of the EPIC physical activity questionnaire: A validation study using accelerometers as an objective measure. Int J Behav Nutr Phys Act. 2008;5:33. doi: 10.1186/1479-5868-5-33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Ainsworth BE, Haskell WL, Herrmann SD, et al. 2011 Compendium of Physical Activities: A second update of codes and MET values. Med Sci Sports Exerc. 2011;43:1575–1581. doi: 10.1249/MSS.0b013e31821ece12. [DOI] [PubMed] [Google Scholar]
- 15.Littman AJ, Tang MT, Rossing MA. Longitudinal study of recreational physical activity in breast cancer survivors. J Cancer Surviv. 2010;4:119–127. doi: 10.1007/s11764-009-0113-2. [DOI] [PubMed] [Google Scholar]
- 16.Huy C, Schmidt ME, Vrieling A, et al. Physical activity in a German breast cancer patient cohort: One-year trends and characteristics associated with change in activity level. Eur J Cancer. 2012;48:297–304. doi: 10.1016/j.ejca.2011.08.005. [DOI] [PubMed] [Google Scholar]
- 17.Thompson CL, Owusu C, Nock NL, et al. Race, age, and obesity disparities in adult physical activity levels in breast cancer patients and controls. Front Public Health. 2014;2:150. doi: 10.3389/fpubh.2014.00150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Irwin ML, Crumley D, McTiernan A, et al. Physical activity levels before and after a diagnosis of breast carcinoma: The Health, Eating, Activity, and Lifestyle (HEAL) study. Cancer. 2003;97:1746–1757. doi: 10.1002/cncr.11227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Mandelblatt JS, Makgoeng SB, Luta G, et al. A planned, prospective comparison of short-term quality of life outcomes among older patients with breast cancer treated with standard chemotherapy in a randomized clinical trial vs. an observational study: CALGB #49907 and #369901. J Geriatr Oncol. 2013;4:353–361. doi: 10.1016/j.jgo.2013.05.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Kornblith AB, Lan L, Archer L, et al. Quality of life of older patients with early-stage breast cancer receiving adjuvant chemotherapy: A companion study to cancer and leukemia group B 49907. J Clin Oncol. 2011;29:1022–1028. doi: 10.1200/JCO.2010.29.9859. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Arndt V, Merx H, Stürmer T, et al. Age-specific detriments to quality of life among breast cancer patients one year after diagnosis. Eur J Cancer. 2004;40:673–680. doi: 10.1016/j.ejca.2003.12.007. [DOI] [PubMed] [Google Scholar]
- 22.Kroenke CH, Rosner B, Chen WY, et al. Functional impact of breast cancer by age at diagnosis. J Clin Oncol. 2004;22:1849–1856. doi: 10.1200/JCO.2004.04.173. [DOI] [PubMed] [Google Scholar]
- 23.Ganz PA, Guadagnoli E, Landrum MB, et al. Breast cancer in older women: Quality of life and psychosocial adjustment in the 15 months after diagnosis. J Clin Oncol. 2003;21:4027–4033. doi: 10.1200/JCO.2003.08.097. [DOI] [PubMed] [Google Scholar]
- 24.Kwan ML, Sternfeld B, Ergas IJ, et al. Change in physical activity during active treatment in a prospective study of breast cancer survivors. Breast Cancer Res Treat. 2012;131:679–690. doi: 10.1007/s10549-011-1788-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Tonosaki A, Ishikawa M. Physical activity intensity and health status perception of breast cancer patients undergoing adjuvant chemotherapy. Eur J Oncol Nurs. 2014;18:132–139. doi: 10.1016/j.ejon.2013.11.008. [DOI] [PubMed] [Google Scholar]
- 26.van de Water W, Kiderlen M, Bastiaannet E, et al. External validity of a trial comprised of elderly patients with hormone receptor-positive breast cancer. J Natl Cancer Inst. 2014;106:dju051. doi: 10.1093/jnci/dju051. [DOI] [PubMed] [Google Scholar]
- 27.Repetto L, Fratino L, Audisio RA, et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: An Italian Group for Geriatric Oncology Study. J Clin Oncol. 2002;20:494–502. doi: 10.1200/JCO.2002.20.2.494. [DOI] [PubMed] [Google Scholar]
- 28.Li D, de Glas NA, Hurria A. Cancer and aging: general principles, biology, and geriatric assessment. Clin Geriatr Med. 2016;32:1–15. doi: 10.1016/j.cger.2015.08.003. [DOI] [PubMed] [Google Scholar]
- 29.Wildiers H, Heeren p, Puts M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32:2595–2603. doi: 10.1200/JCO.2013.54.8347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.van de Water W, Kiderlen M, Bastiaannet E, et al. External validity of a trial comprising elderly patients with hormone-receptor positive breast cancer. J Natl Cancer Inst. 2014 doi: 10.1093/jnci/dju051. [DOI] [PubMed] [Google Scholar]
- 31.Mishra SI, Scherer RW, Geigle PM, et al. Exercise interventions on health-related quality of life for cancer survivors. Cochrane Database Syst Rev. 2012;8:CD007566. doi: 10.1002/14651858.CD007566.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Morey MC, Snyder DC, Sloane R, et al. Effects of home-based diet and exercise on functional outcomes among older, overweight long-term cancer survivors: RENEW: A randomized controlled trial. JAMA. 2009;301:1883–1891. doi: 10.1001/jama.2009.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Biganzoli L, Wildiers H, Oakman C, et al. Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA) Lancet Oncol. 2012;13:e148–e160. doi: 10.1016/S1470-2045(11)70383-7. [DOI] [PubMed] [Google Scholar]
- 34.Wildiers H, Mauer M, Pallis A, et al. End points and trial design in geriatric oncology research: A joint European organisation for research and treatment of cancer--Alliance for Clinical Trials in Oncology—International Society Of Geriatric Oncology position article. J Clin Oncol. 2013;31:3711–3718. doi: 10.1200/JCO.2013.49.6125. [DOI] [PubMed] [Google Scholar]
- 35.de Glas NA, Hamaker ME, Kiderlen M, et al. Choosing relevant endpoints for older breast cancer patients in clinical trials: An overview of all current clinical trials on breast cancer treatment. Breast Cancer Res Treat. 2014;146:591–597. doi: 10.1007/s10549-014-3038-z. [DOI] [PubMed] [Google Scholar]