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In the United States and other developed nations breast cancer incidence and mortality rates rise dramatically with increasing age. This fact, coupled with the aging of the U.S population is leading to a tsunami of older women with breast cancer. Most oncologists lack training in geriatrics and the frequent comorbidities in older patients along with a new diagnosis of breast cancer makes treatment selection challenging. Little data from clinical trials are available to guide physicians in treatment selection and a paucity of geriatricians makes it difficult to develop comprehensive treatment plans for many older patients. Newer tools that are validated, fast, and user-friendly are now available to help busy clinicians do meaningful geriatric assessments which are necessary for evaluating the medical, functional, cognitive, psychological, and social status of older patients. Such tools can be used to accurately estimate survival in older patients and more recently to predict chemotherapy related toxicity. For older patients, maintenance of independent living and cognitive function are their major goals and such preferences must be taken into consideration when planning treatment. Older women, like younger women, are interested in body image and when possible should be offered breast preservation with lumpectomy and radiation. In some older women treated with lumpectomy and adjuvant endocrine therapy for small tumors that are hormone-receptor positive and lower grade, breast radiation may be omitted with only a small increase in the risk of in-breast recurrence. The majority of older patients with early stage breast cancer have hormone receptor positive, HER-2 negative breast cancers and are excellent candidates for endocrine therapy. The major issue in these patients is defining the potential added value of chemotherapy. Elders with HER-2 positive tumors may be good candidates for chemotherapy and trastuzumab, while for many with "triple-negative" lesions, chemotherapy is the option of choice. Older patients with metastatic breast cancer whose tumors have progressed after endocrine therapy can be considered for palliative chemotherapy and many single agent regimens are well tolerated in this setting. In these patients, making sure they are offered "structured" palliative care as part of their treatment program is integral to maximizing quality of life and possibly even prolonging survival. Lastly, eligible elders should be offered clinical trials participation. Although getting elders on trials remains a challenge, it's essential we work diligently on recruitment so as to obtain meaningful data on outcomes and toxicities of newer treatment regimens. Opportunities for trials of all types abound, not only for testing new treatments, but for defining interventions that minimize toxicity and loss of function. All of us in oncology will need to learn how to care for older cancer patients to provide them with optimal treatment. [ABSTRACT FROM AUTHOR]

The article offers the author's views on cancer treatment for older people. He points out the need to overcome the bias against offering potentially beneficial chemotherapy to older patients, encouraging leaders in the fields of gerontology and oncology to educate physicians and the public about the appropriate use of the therapy in such patients.

An abstract of the article "Standard Chemotherapy (CMF or AC) vs Capecitabine in Early-Stage Breast Cancer Patients Aged 65 and Older: Results of CALGB/CTSU 49907," by H.B. Muss and colleagues, is presented.

Background: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor-positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence.Methods: We conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival.Results: We enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5-year disease-free survival rate was 95% (95% confidence interval [CI], 93 to 96) with letrozole and 91% (95% CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P=0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93% (95% CI, 92 to 95) with letrozole and 94% (95% CI, 92 to 95) with placebo (hazard ratio, 0.97; P=0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21% (95% CI, 0.10 to 0.32), and the rate in the placebo group was 0.49% (95% CI, 0.32 to 0.67) (hazard ratio, 0.42; P=0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life.Conclusions: The extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov numbers, NCT00003140 and NCT00754845.). [ABSTRACT FROM AUTHOR]

Background: Cognitive changes for older women who receive chemotherapy are poorly understood. Methods: Cancer and Leukemia Group B (CALGB) 49907 enrolled 633 women ±65 years with early stage breast cancer and randomized them to standard adjuvant chemotherapy (AC or CMF) or capecitabine (N Eng J Med 360:2055, 2009). Patients enrolled on the Quality of Life companion study (N = 350) included women who had cognitive and psychological functioning sufficient for providing informed consent and participation in the trial (J Clin Oncol 29:1022, 2011). Participants completed an 18 item questionnaire focusing on their subjective report of cognitive function (attention, problem-solving, speed, new learning, and remote memory) at 6 time points (baseline, mid-treatment, within 1 month post treatment, and at 12, 18, and 24 months post treatment). Possible scores for each item ranged from 1-7 ('above average' - 'severe problem'). Cognitive function score (CFS) was defined as the mean score of items 1-18. Cognitive impairment was defined as CFS 1.5 standard deviations above the overall average baseline. Univariate associations were tested between baseline CFS and patient characteristics (treatment, race, education, number of positive nodes, hormone receptor status, HER2 status, performance status, number of comorbidities, fatigue and depression) using Kruskal-Wallis testing. Frequency distributions were used to describe cognitive impairment. Multivariate analyses were not completed because few women reported subjective cognitive impairment during the study period. Results: 297 assessments were received at baseline, 280 at both mid-treatment and within 1 month post-treatment, 259 at 12 months, 245 at 18 months and 240 at 24 months post- treatment. The median age was 72 (65-85); 32% received AC, 21% CMF, and 47% capecitabine. Most women were white (87%) and had a performance status of 0 (73%). Approximately half of women had a high school degree or less and the majority had stage I-II (78%), hormone-receptor positive (68%) cancers and most did not experience depression or fatigue at baseline. At baseline, the overall mean CFS was 2.1 ('normal ability') and 19 women (6%) had mild to severe impairment. Baseline scores did not differ by treatment (p = 0.35). Worse cognitive function at baseline was associated with less education (p < 0.01), increased number of positive nodes (p = 0.02), 4+ comorbid conditions (p < 0.01) and fatigue (p = 0.02), although differences for these groups were small. During the study period, overall mean cognitive function scores remained at 'normal ability'. At mid-treatment, within 1 month post treatment, 12, 18 and 24 months, cognitive impairment was present in 19 (6%), 19 (6%), 29 (10%), 31 (12%), 18 (7%), and 22 (9%), respectively. Conclusions: Our data suggest that in a healthy group of women without baseline cognitive impairments on objective screening, chemotherapy does not seem to be associated with changes in self-reported cognitive function over time. [ABSTRACT FROM AUTHOR]

Purpose: To identify needs of metastatic breast cancer patients prior to starting a new systemic treatment., Methods: Fifty patients with newly diagnosed, recurrent, or progressive metastatic breast cancer completed an electronic survey which included patient-reported outcome measures of function (PROMIS Cancer Function Brief 3D profile), quality of life (FACT-G), exercise (Godin Leisure-Time exercise questionnaire), and diet (REAP-S); demographic information; and self-reported use of or referral to specific resources at the cancer center prior to beginning a new systemic oncologic treatment., Results: Prior to starting a new treatment for metastatic breast cancer, patients reported mild functional impairment (PROMIS Cancer Function Brief 3D profile mean score:42.1) and low quality of life (FACT-G: 50%) along with low diet quality (REAP-S mean score: 29). Fifty-two percent of patients were sedentary (Godin Leisure-Time exercise questionnaire) and major barriers to exercise were pain (38%) and fatigue (34%); however, patients expressed a high level of interest (86%) in improving their ability to tolerate cancer treatment by addressing these areas., Conclusion: Patients with new or recurrent metastatic breast cancer face health-related issues including sedentary behavior, poor diet, and limitations including pain and fatigue that can be addressed in prehabilitative efforts prior to starting a new oncologic treatment., Competing Interests: Declarations. Conflict of interest: SEK received unrelated speaker honorarium from Harvard Medical School. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the institutional review board at the University of North Carolina., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: In light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy., Methods: In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS). SET2,3 was tested on the 682 banked RNA samples from ER+ cancers., Results: Dose-dense chemotherapy improved DFS in the overall study population by 23% (HR, 0.77 [95% CI, 0.66 to 0.90]) and OS by 20% (HR, 0.80 [95% CI, 0.67 to 0.95]); the benefits of dose-dense therapy were seen for ER+ and ER-negative subsets, without significant interaction between treatment arm and ER status. Low SET2,3 status was highly prognostic, but also predicted improved outcomes from dose-dense chemotherapy (interaction P = .0998 for DFS; 0.027 for OS), independent of menopausal status. Specifically, low endocrine transcriptional activity predicted benefit from dose-dense chemotherapy, whereas tumor burden and proliferation-driven signatures for molecular subtype classification did not., Conclusion: At 12-year follow-up, C9741 confirmed the sustained long-term benefit of adjuvant dose-dense chemotherapy for node-positive breast cancer. SET2,3 identified patients with ER+ breast cancer who benefited from dose-dense chemotherapy, and specifically, this benefit was predicted by low endocrine activity in the cancer, rather than tumor burden, molecular subtype, or menopausal status.

Background: Pre-treatment characteristics of women with early breast cancer that are associated with persistent fatigue or suboptimal health-related quality of life (HRQOL) post-chemotherapy need to be identified as potential targets for pre-habilitation., Patients and Methods: Ancillary analysis of previously collected data from patients with newly diagnosed Stage I-III breast cancer scheduled to receive chemotherapy. The objective was to identify baseline (pre-chemotherapy) variables associated with meaningful deteriorations in fatigue and other measures of HRQOL from pre-treatment to 6 months after chemotherapy completion. Percentages are reported along with unadjusted and adjusted relative risks., Results: In a sample of 249 women post-chemotherapy, 32% reported worsening fatigue (FACIT-F), 35% worsening Physical Well-Being (PWB), 16% worsening Functional Well-Being (FWB), 8% worsening Emotional Well-Being (EWB), and 30% worsening Social Well-Being (SWB). In multivariable (MV) analysis, variables that were significant in univariate analysis - Black race, high BMI, and baseline poorer EWB - remained significant for worsening post-chemotherapy fatigue (FACIT-F). In MV analysis that included race, education, falls, and baseline EWB, Black race and a positive falls history remained significant for worsening PWB. In MV analysis inclusive of race, Short Physical Performance Battery (SPPB) and FWB, lower SPPB and FWB remained significant predictors of worsening FWB. In MV analysis that included baseline Mental Health Index-Anxiety, EWB and SWB, a higher SWB and lower EWB remained significant for worsening SWB., Conclusion: Pre-chemotherapy characteristics in women with early-stage breast cancer that are associated with increased fatigue and reduced HRQOL post-treatment could be used to identify patients who may benefit from pre-habilitation interventions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In the field of exercise oncology, there is a need to quantify the potential benefits of moderate, self-directed physical activity during active treatment. In a pooled analysis of three identical single-arm intervention studies, we investigate the association of activity tracker steps with patient-reported toxicities during chemotherapy., Methods: Women with early breast cancer who were enrolled in the intervention studies reported their symptom severity every 2-3 weeks throughout chemotherapy, and daily steps were documented through a Fitbit activity tracker. Relative risks (RR) and 95% confidence intervals (CI) were calculated using Poisson regression models with robust variance. For outcomes significant in unadjusted models, adjusted RRs were calculated controlling for race, age, and education level. Tracker step cut point (high step, low step) was determined by the means. Cumulative incidence functions of moderate, severe, and very severe (MSVS) symptoms were estimated using the Kaplan-Meier method and compared using a Cox proportional hazard model., Results: In a sample of 283 women, mean age was 56 years and 76% were White. Mean tracker-documented steps/week were 29,625, with 55% walking below the mean (low step) and 45% above (high step). In multivariable analysis, high step patients had lower risk for fatigue [RR 0.83 (0.70, 0.99)] (p = 0.04), anxiety [RR 0.59 (0.42, 0.84)] (p = 0.003), nausea [RR 0.66 (0.46, 0.96)] (p = 0.03), depression [RR 0.59 (0.37, 0.03)] (p = 0.02), and ≥ 6 MSVS symptoms [RR 0.73 (0.54, 1.00)] (p = 0.05) and had 36% lower risk for dose reductions [RR 0.64 (95% CI 0.43, 0.97)] (p = 0.03)., Conclusion: Self-directed walking at a rate of at least 30,000 steps/week may moderate the severity of treatment side effects during chemotherapy for early breast cancer., Trial Numbers: NCT02167932, NCT02328313, NCT03761706., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Adults 65 years of age or older with metastatic cancer face complicated treatment decisions. Few studies have explored the process with oncology clinicians during clinic encounters. Our exploratory study evaluated whether symptom burden or functional status impacted treatment decision conversations between older adults, caregivers, and oncology clinicians in a single National Cancer Institute within the Mountain West region., Materials and Methods: We conducted an observational, convergent mixed methods longitudinal study between November 2019 and January 2021; participants were followed for six months. The MD Anderson Symptom Inventory (MDASI) and Katz Index of Independence in Activities of Daily Living (ADL) were administered prior to clinical encounter. Ambulatory clinic encounters were audio recorded, transcribed, and analyzed. Nineteen older adults with a metastatic cancer diagnosis or a relapsed refractory hematologic malignancy were approached to achieve a sample of fifteen participants. The main outcome of interest was the number and quality of treatment decision making conversations, defined broadly and encompassing any interaction between the participant and oncology provider that involved (a) an issue or concern (e.g., symptoms, quality of life) brought up by anyone in the room during the clinical encounter, (b) a clinician addressing the concern, or (c) the patient or caregiver making a decision that involved a discussion of their goals or treatment preferences., Results: Nine men and six women with a mean age of 71.3 years (6.6; standard deviation [SD]) were enrolled, and four died while on study. Participants were followed from one to ten visits (mean 4.5; SD 2.8) over one to six months. Of the 67 analyzed encounters, seven encounter conversations (10%) were identified as involving any type of treatment decision discussion. The seven treatment decision conversations occurred with five participants, all male (although female participants made up 40% of the sample), and 63% of participants who reported severe symptoms on the MDASI were female. Severe symptoms or functional status did not impact treatment conversations., Discussion: Our results suggest that older adults with incurable cancer and their oncology clinicians do not spontaneously engage in an assessment of costs and benefits to the patient, even in the setting of palliative treatment and significant symptom burden., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Older breast cancer survivors are at increased risk of clinical decline after adjuvant chemotherapy. This study aimed to evaluate whether inflammatory markers assessed before adjuvant chemotherapy are associated with chemotherapy-induced clinical decline in a population of fit older adults with breast cancer., Methods: In a prospective study of women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy, we measured interleukin-6 (IL-6) and C-reactive protein (CRP) prechemotherapy (T1). We assessed frailty status, using a Deficit Accumulation Index (DAI; categorized as robust, prefrail, and frail), at T1 and postchemotherapy (T2). The population of interest was robust women at T1. The primary outcome was chemotherapy-induced decline in frailty status, defined as decline in DAI from robust (T1) to prefrail or frail (T2). Multivariable logistic regression was used to examine the association between inflammatory markers and the primary outcome, adjusted for sociodemographic and clinical characteristics., Results: Of the 295 robust women at T1, 76 (26%) experienced chemotherapy-induced decline in frailty status, among whom 66% had high IL-6, 63% had high CRP, and 46% had high IL-6 and CRP at T1. After adjusting for sociodemographic and clinical characteristics, women with high IL-6 and CRP had a > three-fold (odds ratio, 3.52; 95% CI, 1.55 to 8.01; P = .003) odds of chemotherapy-induced decline in frailty status compared with women with low IL-6 and CRP., Conclusion: In this cohort of older women with early breast cancer who were clinically fit before chemotherapy initiation, high IL-6 and CRP prechemotherapy were associated with chemotherapy-induced decline in frailty status independent of sociodemographic and clinical risk factors. Further research is needed to examine whether inflammatory markers can inform more personalized approaches to treating older breast cancer survivors.

Background and Objectives: Novel, non-cytotoxic agents are driving a paradigm shift for treatment of older adults with acute myeloid leukemia (AML). Older patients who initially receive intensive cytotoxic induction may choose to not proceed with cytotoxic consolidation therapy. Lenalidomide is an orally-administered immunomodulatory small molecule with activity in AML and a favorable safety profile in older adults with active leukemia. We conducted a phase Ib study of lenalidomide as post-remission therapy in older adults and assessed its impact on geriatric functional domains., Materials and Methods: Participants were patients with AML over age 60 years who had undergone induction therapy and were poor candidates for cytotoxic consolidation. Lenalidomide was administered for 28 days in three dose cohorts. A Bayesian dose-escalation method determined cohort assignment and maximum tolerated dose (MTD). Geriatric assessment (GA) was performed before and after the cycle of lenalidomide., Results: Nineteen patients with median age 68 were treated with at least one 28-day course of lenalidomide. Dose-limiting toxicities were observed in three participants at 25 mg, zero participants at 35 mg, and one participant at 50 mg. MTD was 35 mg. Median relapse-free survival was 4.3 months. GA was completed before and after treatment in fifteen patients, demonstrating improved cognitive function and no changes in physical, psychological, or social function after lenalidomide., Conclusion: Lenalidomide can be safely administered to older adults with AML with preservation of functional domains important to older patients. Serial GA can be performed in a novel drug study as a tool to characterize treatment tolerability., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Despite the large number of patients with early breast cancer (EBC) who have been treated with capecitabine in randomised trials, no individual patient data meta-analysis has been conducted. The primary objective was to examine the effect of capecitabine on disease-free survival (DFS), and the secondary objectives were to analyse distant DFS (DDFS), overall survival (OS), pathological complete response (for neoadjuvant studies) and the interaction between capecitabine-related toxicity and treatment effect., Methods: www., Clinicaltrials: gov and www.pubmed.ncbi.nlm.nih.gov were searched using the following criteria: use of capecitabine for EBC as adjuvant or neoadjuvant therapy; multicentre randomised trial with >100 patients; recruitment completed, and outcomes available. Required data were available for 13 trials., Results: Individual data from 15,993 patients were collected. Cox regression analyses of all included patients revealed that the addition of capecitabine did not alter DFS significantly compared with treatment without capecitabine (hazard ratio [HR] 0.952; 95% CI 0.895-1.012; P value = 0.115). There was also no effect on DFS in the subset of studies where capecitabine was given instead of another drug (HR 1.035; 95% CI 0.945-1.134; P = 0.455). However, capecitabine administered in addition to the standard systemic treatment improved DFS (HR 0.888; 95% CI 0.817-0.965; P = 0.005). An OS improvement was observed in the entire cohort (HR 0.892; 95% CI 0.824-0.965, P = 0.005) and in the subset of capecitabine addition (HR 0.837; 95% CI 0.751, 0.933, P = 0.001). Subgroup analyses revealed that triple-negative breast cancer (TNBC) patients benefitted from treatment with capecitabine overall and in addition to other systemic treatments in terms of DFS and OS., Conclusion: Capecitabine was able to improve DFS and OS in patients with TNBC and in all patients with EBC when administered in addition to systemic treatment., Competing Interests: Conflict of interest statement M.v.M. reports personal fees from AstraZeneca, personal fees from Amgen, personal fees from Novartis, personal fees from Genomic Health, personal fees from Gilead, personal fees from GSK, personal fees from Lilly, personal fees from Molecular Health, personal fees from Mylan, personal fees from Pfizer, personal fees from Roche, personal fees from Pierre Fabre, personal fees from Seagen, outside the submitted work; V.M. reports speaker honoraria from Amgen, AstraZeneca, Celgene, Roche, Teva, consultancy honoraria from Roche, Amgen, TESARO and Myelo Therapeutics; J.O.S. reports personal fees from AbbVie, personal fees from Agendia, personal fees from AstraZeneca, personal fees from Bristol-Myers Squibb, personal fees from Celgene, personal fees from Eisai, personal fees from Genentech, personal fees from Immunomedics, personal fees from Ipsen, personal fees from Jounce, personal fees from Lilly, personal fees from Merck, personal fees from Myriad, personal fees from Novartis, personal fees from Ondonate Therapeutics, personal fees from Pfizer, personal fees from Puma, personal fees from Roche, personal fees from Seattle Genetics, personal fees from Prime Oncology, outside the submitted work; M.M. has received research grants from Roche, PUMA and Novartis, consulting/advisory fees from AstraZeneca, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology, Daiichi Sankyo and Pfizer and speakers' honoraria from AstraZeneca, Lilly, Amgen, Roche/Genentech, Novartis and Pfizer, outside the submitted work. H.J. reports personal fees from Orion Pharma, personal fees from Neutron Therapeutics, other from Orion Pharma, other from Sartar Therapeutics, outside the submitted work. M.U. reports personal fees and non-financial support from AbbVie, personal fees and non-financial support from Amgen GmbH, personal fees and non-financial support from Astra Zeneca, personal fees from BMS, personal fees and non-financial support from Celgene GmbH, personal fees and non-financial support from Daiichi Sankyo, personal fees and non-financial support from Eisai GmbH, personal fees from Lilly Deutschland, personal fees and non-financial support from Lilly Int., personal fees and non-financial support from MSD Merck, personal fees and non-financial support from Mundipharma, personal fees and non-financial support from Myriad Genetics, personal fees and non-financial support from Odonate, personal fees and non-financial support from Pfizer GmbH, personal fees from PUMA Biotechnology, personal fees and non-financial support from Roche Pharma AG, personal fees and non-financial support from Sanofi Aventis Deutschland GmbH, personal fees and non-financial support from TEVA Pharmaceuticals Ind Ltd, personal fees and non-financial support from Novartis, personal fees from Pierre Fabre, personal fees and non-financial support from Clovis Oncology, personal fees from Seattle Genetics, outside the submitted work; U.N. reports grants and personal fees from Agendia, grants and personal fees from Amgen, grants and personal fees from Celgene, grants, personal fees and other from Genomic Health, grants and personal fees from NanoString Technologies, personal fees from Novartis, personal fees and other from Pfizer, grants, personal fees and other from Roche/Genentech, personal fees from Teva, grants from Sanofi, outside the submitted work. G.S. reports personal fees and non-financial support from Roche, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Novartis, personal fees from Lilly, non-financial support from TEVA, personal fees and non-financial support from Pfizer, outside the submitted work. C.H.B. reports grants/research support from (to the institution) Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas Pharma, BioMarin, Bristol-Myers Squibb, Daiichi Sankyo, Abraxis BioScience, AB Science, Asana Biosciences, Medivation, Exelixis, ImClone Systems, LEO Pharma, Millennium, Merck KGaA, Shanghai Henlius Biotech, Polyphor, PharmaMar; Advisory boards and consulting: Boehringer Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, Astra Zeneca, Zodiac, Lilly, Sanofi. HDB reports other from Merck, other from Pfizer, other from AbbVie, outside the submitted work. M.T. reports grants and personal fees from Chugai, grants and personal fees from Takeda, grants and personal fees from Pfizer, grants and personal fees from Kyowa-Hakko-Kirin, grants and personal fees from C & C Res Lab, grants and personal fees from Taiho, grants from JBCRG association, grants and personal fees from Eisai, grants and personal fees from Daiichi-Sankyo, grants and personal fees from Astra Zeneca, personal fees from Eli Lilly, personal fees from MSD, personal fees from Genomic Health, personal fees from Novartis, personal fees from Konica Minolta, grants from Astellas, outside the submitted work; and Board of directors; JBCRG association, Organisation for Oncology and Translational Research, Kyoto Breast cancer Research Network. H.M. reports grants from NCI grant to Alliance/CALGB, during the conduct of the study. T.R. reports personal fees from Roche, during the conduct of the study. S.L. reports grants and other from Roche, during the conduct of the study; grants and other from AbbVie, grants and other from Celgene, other from Seattle Genetics, other from PriME/Medscape, personal fees from Chugai, grants and other from Daiichi-Sankyo, other from Lilly, other from Samsung, other from BMS, other from Puma, grants from Immunomedics, grants and other from AstraZeneca, other from Pierre Fabre, other from Merck, other from GlaxoSmithKline, other from EirGenix, grants and other from Bayer, grants and other from Amgen, grants and other from Novartis, grants and other from Pfizer, outside the submitted work; In addition, S.L. has a patent EP14153692.0 pending. All remaining authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Insufficient social support is associated with increased mortality among older adults. Lung cancer is primarily a disease of older adults and is the leading cause of all cancer deaths. We assessed the association of social support with outcomes among older adults with lung cancer., Materials and Methods: Adults age 65 and older with lung cancer with a completed geriatric assessment (GA) were assessed. Emotional social support (ES) and tangible (material, instrumental) support (TS) measures and patient characteristics were obtained from the GA. The electronic health record was used to extract clinical variables. Simple linear regression models evaluated the association between social support scales with patient and clinical factors., Results: 79 adults were assessed. White race was positively associated with ES score (p=.04), while higher BMI (p=.03), depression (p=.03) and anxiety (p=.02) were associated with worse ES. Higher BMI was associated with higher/better TS score (p=.02) while living alone was associated with lower/worse TS score (p=.03). Completion of platinum-based doublet chemotherapy with immunotherapy as planned was associated with higher ES scores (p=.02) and higher TS scores (p=.02). Disease progression was associated with lower ES scores (p=.03)., Conclusion: Social support may influence clinical outcomes in older adults with lung cancer. As lung cancer often portends to poor prognosis, social support may be an important prognostic indicator., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: Triple negative breast cancer (TNBC) is characterized by the presence of immune cells in the tumor microenvironment, however, the response to single-agent immune checkpoint inhibitor (ICI) therapy is modest. Preclinical models have demonstrated that intratumoral regulatory T cells (T regs ) dampen the antitumor response to ICI. We performed a single-arm phase II trial to evaluate the efficacy of a single low dose of cyclophosphamide (Cy) to deplete T regs administered before initiating pembrolizumab., Patients and Methods: 40 patients with pretreated metastatic TNBC were enrolled. The primary endpoints were progression-free survival (PFS) and change in peripheral blood T regs after Cy. Secondary endpoints included overall response rate (ORR), duration of response, overall survival, treatment-related adverse events (AEs), and correlative evaluations., Results: Median PFS was 1.8 months, and the ORR was 21%. T regs were not significantly decreased after Cy prior to ICI (-3.3%, p=0.19), and increased significantly after the first cycle of therapy (+21% between cycles 1 and 2, p=0.005). Immune-related AEs were similar to historical pembrolizumab monotherapy, and were associated with response to therapy (p=0.02). Patients with pretreatment tumors harboring increased expression of B cell metagene signatures and increased circulating B cell receptor repertoire diversity were associated with clinical response and immune-related toxicity (IRT)., Conclusions: Among patients with heavily pretreated TNBC, Cy prior to pembrolizumab did not significantly deplete T regs , and in those with decreased numbers there was rapid recovery following therapy. Increased B cell gene expression in baseline samples was associated with clinical response and IRT., Competing Interests: Competing interests: CKA receives research funding from PUMA, Lilly, MSD, Seattle Genetics, Nektar, Tesaro, and G1 Therapeutics, ZION, Novartis, Pfizer; compensation for consulting from Genentech, Eisai, IPSEN, Seattle Genetics, AstraZeneca, Novartis; and royalties from UpToDate and Jones and Bartlett. BV holds equity in GeneCentric Therapeutics. CP is an equity stockholder and consultant of BioClassifier, and an equity stock holder, consultant, and Board of Directors member of GeneCentric Therapeutics. CP is also listed as an inventor on patent applications for the Breast PAM50 assay. JS receives funding from MSD, GSK, and Carisma, is a scientific consultant for PIQUE Therapeutics and has filed IP for the use of STING agonists to enhance CAR T cell for breast cancer. The other authors have no conflicts requiring disclosure., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Older adults are under-represented in cancer clinical trials. However, it remains unclear which types of trials under-enroll aging patients. We aimed to identify associations between trial characteristics and disparate enrollment of older adults onto trials sponsored by the Alliance for Clinical Trials in Oncology (Alliance)., Methods: Actual age ≥ 65 percentage and trial data were extracted from the Alliance closed study list. Each trial, based on its cancer type and years of enrollment, was assigned an expected age ≥ 65 percentage extracted from the Surveillance, Epidemiology, and End Results (SEER) US population-based database. Enrollment disparity difference (EDD), the difference between the expected age ≥ 65 percentage and the actual age ≥ 65 percentage, was calculated for each trial. Linear regression determined trial variables associated with larger EDDs and variables with an overall association p-value <0.20 were included in a multivariable fixed-effects linear model., Results: The median age of 66,708 patients across 237 trials was 60 years (range 18-102). The average actual age ≥ 65 percentage enrolled per trial was lower than each trial's expected age ≥ 65 percentage average (39% vs. 58%; EDD 19, 95% CI 17.1-21.3%, p < 0.0001). In multivariable analyses, non-genitourinary (GU) cancer types (p < 0.001), trimodality+ trials (estimate 8.78, 95%CI 2.21-15.34, p = 0.009), and phase 2 trials (estimate 4.43 95% CI -0.06-8.91; p = 0.05) were all associated with larger EDDs., Conclusions: Disparate enrollment of older adults is not equal across cancer trials. Future strategies to improve older adult inclusion should focus on trial types associated with the highest disparate enrollment., Competing Interests: Declaration of Competing Interest NV reports advisory board member for Concerto Health AI. RJ has stock options as compensation for her advisory board role in Equity Quotient, a company that evaluates culture in health care companies; she has received personal fees from Amgen and Vizient and grants for unrelated work from the National Institutes of Health, the Doris Duke Foundation, the Greenwall Foundation, the Komen Foundation, and Blue Cross Blue Shield of Michigan for the Michigan Radiation Oncology Quality Consortium. She has a contract to conduct an investigator initiated study with Genentech. She has served as an expert witness for Sherinian and Hasso and Dressman Benzinger LaVelle. She is an uncompensated founding member of TIME'S UP Healthcare and a member of the Board of Directors of ASCO., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Patients with cancer have widely divergent experiences throughout their care from screening through survivorship. Differences in care delivery and outcomes may be due to varying patient preferences, patient needs according to stage of life, access to care, and implicit or explicit bias in care according to patient age. NCCN convened a series of stakeholder meetings with patients, caregivers, and patient advocacy groups to discuss the complex challenges and robust opportunities in this space. These meetings informed the NCCN Virtual Patient Advocacy Summit: Cancer Across the Lifespan held on December 10, 2020, which featured a keynote presentation, multidisciplinary panels, and presentations from patient advocacy organizations. This article encapsulates and expounds upon the findings from the stakeholder meetings and discussions during the summit.

Purpose: To assess potential disparities in guideline-concordant care delivery among women with early-stage triple-negative and HER2-positive breast cancer treated with breast conserving therapy., Methods: Women ≥ 40 years old diagnosed with pT2N0M0 triple-negative or HER2-positive breast cancer treated with primary surgery and axillary staging between 2012 and 2017 were identified using the National Cancer Database (NCDB). The primary outcome was receipt of adjuvant systemic therapy and radiation concordant with current guidelines. Multivariable log-binomial regression was used to assess the prevalence of optimal therapy use across patient and cancer characteristics. Kaplan-Meier curves were used to assess 5-year overall survival. Multivariable Cox proportional hazards regression was used to compare the impact of optimal therapy on 5-year mortality., Results: 11,785 women were included with 7,843 receiving optimal therapy. Receipt of optimal therapy decreased with age even after adjusting for comorbidities and cancer characteristics; other sociodemographic factors were not associated with differences in receipt of optimal therapy. Among patients who did not receive adjuvant systemic therapy, most were not offered the treatment (49%) or refused (40%). Overall 5-year survival was higher among women who received optimal therapy (89% [95% CI 88.0-89.3] vs. 66% [95% CI 62.9-68.5]). Patients who received suboptimal therapy were over twice as likely to die within 5 years of their diagnosis (adjusted HR 2.44, 95% CI 2.12-2.82)., Conclusion: Age is the primary determinant of the likelihood of a woman to receive optimal adjuvant therapies in high-risk early-stage breast cancer. Patients who did not receive optimal therapy had significantly diminished survival., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Stuart LichtmanConsulting or Advisory Role: Remedy One, Magellan Health.No other potential conflicts of interest were reported.

Purpose: This study determined whether an electronic version of the geriatric assessment is feasible in a multi-institutional, diverse setting., Methods: Ten sites within the Alliance for Clinical Trials in Oncology participated. Patients who had active cancer or a history of cancer and were 65 years of age or older were eligible. The geriatric assessment was completed with an electronic data capture system that had been loaded onto iPads. Feasibility was defined a priori as completion in at least 70% of patients either with or without help. To enhance racial diversity, the original sample size was later changed and augmented by 50% with the intention of increasing enrollment of older minority patients., Results: A total of one hundred fifty-four patients were registered with a median age of 72 years (range, 65-91 years). Forty-three (28%) identified themselves as African American or Black. One hundred forty-one patients (92%) completed the electronic geriatric assessment. Feasibility was observed across all subgroups, regardless of race, education, performance status, comorbidities, and cognition; 124 patients (81%) completed the geriatric assessment without help. Reasons for not completing the geriatric assessment are as follows: clinic visit did not occur (n = 6), no iPad connection to the Internet (n = 3), patient declined (n = 2), prolonged hospitalization (n = 1), and patient died (n = 1). Reasons for needing help, as reported by study personnel, were as follows: the patient preferred that research personnel ask the questions (n = 9), vision problem (n = 3), lack of comfort with the iPad (n = 2), questions were not clear (n = 1), less proficient in English (n = 1), and challenge in pressing the green button to go to the next question (n = 1)., Conclusion: The electronic geriatric assessment is feasible in a multi-institutional setting that includes a notable proportion of African American or Black patients.

Background: Fatigue is a common side effect of radiation therapy and can dramatically affect the quality of life in older cancer patients. We compared a home-based graduated walking intervention with a fixed walking recommendation.recommendation to exercise to determine the effects of these interventions during adjuvant radiotherapy (RT) on older women with breast cancer., Methods: A randomized phase 2 trial in women ≥65 years, with stage 0-3 breast cancer. Prior to initiating breast RT, women were randomized to a Home-Based Graduated Walking Program (HBGWP) or a fixed walking recommendation. The primary outcome of fatigue was measured by the Total Disruption Index (TDI) of the Fatigue Symptom Inventory (FSI). Secondary outcomes including a short physical performance battery (SPPB) and questionnaires on exercise, physical function, fatigue (PROMIS Fatigue), and fatigue-related symptoms were collected at 3 time points. The primary goal was to compare the change in TDI between arms at the end of RT. Random coefficients models were used to determine the association between arm, fatigue, and exercise over time. Linear regression models were used to describe the change in outcome variables between visits., Results: Median age of the 54 participants (27 per arm) was 69 years (range 65-84). The baseline characteristics were similar between study arms. The number of minutes walking per week increased in both arms (mean 21 min/wk. baseline to 83 min/wk. end of RT, p < 0.01) and physical function improved over time in both arms (median 10.5 at baseline to 12 at end of RT, p < 0.01).There was no significant difference in change in TDI between arms (2.7 ± 9.9 vs. 1.8 ± 14.0, p = 0.61)between baseline and end of RT. However, in our linear regression model increasing walking over time was associated with statistically significant lower levels of fatigue (-2.44+/- 1.04, p = 0.04), but not in posthoc subgroup analyses., Conclusion: The HBGWP did not decrease fatigue more than the fixed recommendation to exercise. Both the graduated intervention and fixed recommendation lead to increased walking which was associated with lower fatigue in this study of older adult breast cancer patients., Competing Interests: Declaration of Competing Interest NV: Grants: Conquer Cancer Foundation for the submitted work, personal fees: Concerto HealthAI, outside the submitted work. MB: Personal fees: Novocure LLC, outside the submitted work. AV: Grants and Personal fees: Amgen; personal fees and non-financial support: AstraZeneca, Bristol Myers Squibb, Caris Life Sciences, Roche / Genentech, non-financial support: Merck, Lilly, Replimune; personal fees: Compugen, Immunocore, Concerto HealthAI and institutional support from Nektar Therapeutics, all outside the submitted work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hospitalized older adults have significant geriatric deficits that may lead to poor outcomes. We conducted a randomized trial to investigate the effectiveness of providing clinicians with a real-time geriatric assessment (GA) report in nonelectively hospitalized older patients with cancer., Subjects, Materials, and Methods: We developed a web-based software platform for administering a modified GA (Cancer 2005;104:1998-2005) to older (>70 years) nonelectively hospitalized patients with pathologically confirmed malignancy. Patients were randomized to have their GA report provided to their treating clinicians (Intervention arm) or not provided (Control arm)., Results: Our study included 135 patients, median age 76 years, 52% female, 75% white, 21% black, 79% greater than high school education, 59% married, and 17% living alone. All patients had at least one GA-identified deficit, including physical function deficits (90%), cognitive impairment (22%), >5 comorbidities (28%), polypharmacy (>9 medications; 38%), weight loss ≥10% in the past 6 months (40%), anxiety (32%), or depression (30%). There was no difference between the Intervention (6%) and Control arms (9%) in the proportion of patients who were referred by their clinical team for an intervention to address a deficit (p = .53)., Conclusion: Many older nonelectively hospitalized patients with cancer have geriatric deficits that are amenable to evidence-based interventions. Real-time GA reports provided to the care team prior to discharge did not influence provider referral for such interventions. There is a need for systems-level interventions to address deficits in this vulnerable patient population., Implications for Practice: Geriatric deficits are common in hospitalized older adults with cancer and lead to poor outcomes. Addressing modifiable deficits represents an appealing way to improve outcomes. Widespread geriatrician consultation is impractical owing to resource and personnel constraints. This work tested whether prompt delivery of a mostly self-administered, web-based geriatric assessment report to clinicians improved referral rates for evidence-informed interventions. It confirmed frequent geriatric deficits and high readmission rates in this population but found that real-time geriatric assessment reporting did not influence provider referral for evidence-informed interventions on geriatric assessment identified deficits. These findings highlight the need for systems-level intervention to improve outcomes in this vulnerable patient population., (© AlphaMed Press 2020.)

Background: Nutritional status can directly affect morbidity and mortality in older adults with cancer. This study evaluated the association between pretreatment body mass index (BMI), albumin level, and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors., Methods: This was a secondary analysis of a prospective, multicenter study involving chemotherapy-treated patients 65 years old or older. Geriatric assessment, BMI, albumin level, and UWL data were collected before treatment. Multivariable logistic regression models evaluated the associations between nutritional factors and the risk of grade 3 or higher (grade 3+) chemotherapy toxicity., Results: Seven hundred fifty patients with a median age of 72 years (range, 65-94 years) and mostly stage IV disease were enrolled. The median pretreatment BMI and albumin values were 26 kg/m 2 (range, 15.1-52.1 kg/m 2 ) and 3.9 mg/dL (range, 1.0-5.0 mg/dL), respectively. Nearly 50% of the patients reported UWL, with 17.6% reporting >10% UWL. Multivariable analysis revealed no association between >10% UWL and a risk for grade 3+ chemotherapy toxicity (adjusted odds ratio [AOR], 0.87; P = .58). Multivariable analysis showed a trend toward an association between a BMI ≥ 30 kg/m 2 and a decreased risk of grade 3+ chemotherapy toxicity (AOR, 0.65; P = .06), whereas a low albumin level (≤3.6 mg/dL) was associated with a higher risk of grade 3+ chemotherapy toxicity (AOR, 1.50; P = .03). An analysis of the joint effect of BMI and albumin demonstrated the lowest risk of grade 3+ chemotherapy toxicity among patients with high BMIs (≥30 kg/m 2 ) and normal albumin levels (AOR, 0.41; P = .008)., Conclusions: Among older adults with solid tumors, higher BMIs and normal albumin levels are associated with a lower risk of grade 3+ chemotherapy toxicity. Additional research is warranted to define the clinical significance of nutritional markers and to inform future interventions., (© 2020 American Cancer Society.)

Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report. Dr. Klepin was funded by the CARG R21 grant (R21 AG059206).

Background: The evidence that body composition parameters influence multiple cancer outcomes is rapidly expanding. Excess adiposity deposits in muscle tissue, termed myosteatosis, can be detected in CT scans through variations in the density of muscle tissues (Hounsfield Units). Patients with similar muscle mass but different amounts of intramuscular adipose infiltration have increased chemotherapy toxicity, time to tumor progression and other adverse outcomes among different cancer types. Our review examines the impact of myosteatosis on overall survival (OS) in patients with cancer., Methods: A systematic search of the literature was conducted on PubMed/ MEDLINE, Cochrane CENTRAL, and EMBASE. Meta-analysis was conducted using a random-effects model. Risk of bias was evaluated using the Newcastle-Ottawa Quality assessment for cohort studies, funnel plot (publication bias), and GRADE summary of findings tool from Cochrane., Results: A total of 4880 articles were screened from which 40 articles selected, including 21,222 patients. The overall mean proportion of patients with myosteatosis was 48 % (range 11-85 %). Using skeletal muscle density (SMD), patients classified as having myosteatosis had 75 % greater mortality risk compared to non-myosteatosis patients (HR 1.75 95 % CI 1.60-1.92, 40 studies) (p < .00001) (i2 = 62 %). Specifically, myosteatosis was prognostic for worse OS in patients with gynecological, renal, periampullary/pancreatic, hepatocellular, gastroesophageal, and colorectal carcinoma, and lymphomas., Conclusion: Our analysis of the literature shows that cancer patients with myosteatosis have shorter survival. Our findings suggest that in oncological practice, muscle density assessment is valuable as a prognostic parameter., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Less than 3% of older patients with cancer are enrolled in clinical trials. To reverse this underrepresentation, we compared older patients enrolled with older-patient-specific trials, defined as those designed for older patients with cancer, with those enrolled in age-unspecified trials., Materials and Methods: We focused on individual patient data from those ≥65 years (younger patients excluded) and included all Alliance phase III adjuvant breast cancer trials from 1985-2012., Results: Among 2,277 patients, 1,014 had been enrolled to older-patient-specific and 1,263 to age-unspecified trials. The median age (range) in the older-patient-specific trials was 72 (65-89) years compared with 68 (65-84) years in the cohort of older patients in age-unspecified trials; p < .0001. A greater percentage of patients 75 years or older had enrolled in older-patient-specific trials compared with the cohort of age-unspecified trials: 26% versus 6% ( p < .0001). Median overall survival (OS) was 12.8 years (95% confidence interval [CI], 11.9-13.7) and 13.5 years (95% CI, 12.9-14.1) for older-patient-specific and age-unspecified trials, respectively. OS was comparable (hazard ratio [HR], 1.08; 95% CI, 0.92-1.28; p = .34; referent: age-unspecified trials), after adjusting for age, estrogen receptor status, tumor size, and lymph node status. Similar findings were reached for recurrence-free survival. A lower rate of grade 3-5 adverse events (hematologic and nonhematologic) was reported in older-patient-specific trials (43% vs. 58%; p < .0001). Sensitivity analysis with chemotherapy only trials and subset analysis, adjusted for performance score, yielded similar OS results., Conclusion: Older-patient-specific trials appear to address this underrepresentation of older patients with ostensibly comparable outcomes. Clinical trial identification numbers . NCT00003088 (CALGB 9741); NCT00024102 (CALGB 49907); NCT00068601 (CALGB 40401); NCT00005970 (NCCTG N9831) IMPLICATIONS FOR PRACTICE: This work underscores the importance of clinical trials that focus on the recruitment of older patients with cancer., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Objectives: To analyze self-reported changes in physical function in older women with breast cancer receiving adjuvant chemotherapy., Design: Secondary analysis of the Cancer and Leukemia Group B (CALGB) 49907 prospective randomized clinical trial., Setting: CALGB institutions in the United States., Participants: Women aged 65 and older with Stage I to III breast cancer enrolled in CALGB 49907 who had physical function data from before and after receipt of adjuvant chemotherapy (N=256; mean age 71.5, range 65-85)., Measurements: Participants were administered the physical function subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire before chemotherapy, at the end of chemotherapy, and 12 months after chemotherapy initiation. Functional decline was defined as a more than 10-point decrease from baseline at each time point. Resilience was defined as return to within 10 points of baseline. Multivariable regression was used to examine pretreatment characteristics associated with physical function changes., Results: Of 42% of participants who had physical function decline from before to the end of chemotherapy, 47% recovered by 12 months (were resilient). Almost one-third experienced functional decline from before chemotherapy to 12 months later. Pretreatment fatigue was a risk factor for functional decline from before to the end of chemotherapy (P=.02). Risk factors for functional decline at 12 months included pretreatment dyspnea (P=.007) and being unmarried (P=.01)., Conclusion: Functional decline was common in older women receiving adjuvant chemotherapy for breast cancer in a clinical trial. Although half recovered their physical function, one-third had a clinically meaningful decline at 12 months. Strategies are needed to prevent functional decline in older adults receiving chemotherapy. J Am Geriatr Soc 67:920-927, 2019., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Purpose: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM., Patients and Methods: Eligible patients had progressive HER2 + BCBM. The primary endpoint was intracranial response rate (RR); secondary objectives were CNS clinical benefit rate (CBR), extracranial RR, time to progression (TTP), overall survival (OS), and targeted sequencing of tumors from enrolled patients. A two-stage design distinguished intracranial RR of 5% versus 20%., Results: 32 patients were evaluable for toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was 27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2-5). OS was 12.2 mos (95% CI 0.6-20.2). Grade 3-4 toxicities included neutropenia (41%), anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2 amplification was higher in BCBM compared to primary BC; ERBB2 amplification in the primary BC trended toward worse OS., Conclusion: While intracranial RR to ETV was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar to historical control. No new toxicity signals were observed. Further analysis of the genomic underpinnings of BCBM to identify tractable prognostic and/or predictive biomarkers is warranted., Clinical Trial: (NCT01305941).

Background: Falls in older adults with cancer are common, yet factors associated with fall-risk are not well-defined and may differ from the general geriatric population. This study aims to develop and validate a model of factors associated with prior falls among older adults with cancer., Methods: In this cross-sectional secondary analysis, two cohorts of patients aged ≥ 65 with cancer were examined to develop and validate a model of factors associated with falls in the prior 6 months. Potential independent variables, including demographic and laboratory data and a geriatric assessment (encompassing comorbidities, functional status, physical performance, medications, and psychosocial status), were identified. A multivariate model was developed in the derivation cohort using an exhaustive modeling approach. The model selected for validation offered a low Akaike Information Criteria value and included dichotomized variables for ease of clinical use. This model was then applied in the validation cohort., Results: The development cohort (N = 498) had a mean age of 73 (range 65-91). Nearly one-fifth (18.2%) reported a fall in the prior 6 months. The selected model comprised nine variables involving functional status, objective physical performance, depression, medications, and renal function. The AUC of the model was 0.72 (95% confidence intervals 0.65-0.78). In the validation cohort (N = 250), the prevalence of prior falls was 23.6%. The AUC of the model in the validation cohort was 0.62 (95% confidence intervals 0.51-0.71)., Conclusion: In this study, we developed and validated a model of factors associated with prior falls in older adults with cancer. Future study is needed to examine the utility of such a model in prospectively predicting incident falls.

Objectives: To examine longitudinal symptoms, mobility and function, and quality of life (QOL) in adults newly diagnosed with acute leukemia., Sample & Setting: 55 adults undergoing induction chemotherapy at the University of North Carolina Lineberger Comprehensive Cancer Center and the Duke Cancer Institute., Methods & Variables: A prospective, longitudinal study with measures of mobility and function, global physical and mental health, cancer-related fatigue, anxiety, depression, sleep disturbance, pain intensity, and leukemia-specific QOL was conducted. Data were analyzed using descriptive statistics, linear mixed modeling, and one-way analysis of variance., Results: 49 adults with acute leukemia completed assessments during hospitalizations. Global mental health and pain intensity did not change significantly. Global physical health significantly improved. Fatigue, anxiety, depression, and sleep disturbance decreased significantly. QOL increased significantly., Implications for Nursing: The significant decrease in anxiety and fatigue during hospitalization may be attributable to understanding of the disease process, familiarity with the staff, and ability to communicate concerns.

Objective: This study sought to define the role of first-line platinum-based doublet chemotherapy in older patients with non-small cell lung cancer (NSCLC)., Materials and Methods: We analyzed three first-line NSCLC trials: CALGB 9730, CALGB 30203, and CALGB 30801, which tested carboplatin and paclitaxel; carboplatin and gemcitabine; and carboplatin with either pemetrexed or gemcitabine, respectively. Overall survival was the primary endpoint. Age-based comparisons with a cutpoint of 65 years were performed with Cox proportional hazards models with adjustments for sex, tumor histology, cancer stage, chemotherapy, and smoking history and after stratifying by performance score. Secondary endpoints were grade 3-5 adverse events, chemotherapy cycles completed, and whether toxicity prompted chemotherapy discontinuation., Results: 730 patients were included; 337 (46%) were 65+ years of age. No statistically significant difference in survival was observed for older (≥65) versus younger patients (HR = 1.096; 95% CI = (0.94, 1.28); p = 0.25). A trend emerged with increased odds of a grade 3-5 adverse event for patients ≥65 years versus <65 years (OR = 1.52; 95% CI = (0.99, 2.31); p = 0.05). The proportion of completed chemotherapy cycles was marginally lower in older patients (difference = -5%; 95% CI = (-9, 0.2); p = 0.06) for those ≥65 years versus <65 years, but no statistically significant difference occurred in the rate of chemotherapy discontinuation for toxicity (OR = 1.4; 95% CI = (0.85, 2.19); p = 0.21) for patients ≥65 years versus <65 years. A cutpoint of 70 years yielded similar results., Conclusion: These findings support carboplatin doublet-based chemotherapy in select older patients with advanced NSCLC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose MA.17R was a Canadian Cancer Trials Group-led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor as adjuvant therapy for hormone receptor-positive breast cancer. Quality of life (QOL) was a secondary outcome measure of the study, and here, we report the results of these analyses. Methods QOL was measured using the Short Form-36 (SF-36; two summary scores and eight domains) and menopause-specific QOL (MENQOL; four symptom domains) at baseline and every 12 months up to 60 months. QOL assessment was mandatory for Canadian Cancer Trials Group centers but optional for centers in other groups. Mean change scores from baseline were calculated. Results One thousand nine hundred eighteen women were randomly assigned, and 1,428 women completed the baseline QOL assessment. Compliance with QOL measures was > 85%. Baseline summary scores for the SF-36 physical component summary (47.5 for letrozole and 47.9 for placebo) and mental component summary (55.5 for letrozole and 54.8 for placebo) were close to the population norms of 50. No differences were seen between groups in mean change scores for the SF-36 physical and mental component summaries and the other eight QOL domains except for the role-physical subscale. No difference was found in any of the four domains of the MENQOL Conclusion No clinically significant differences were seen in overall QOL measured by the SF-36 summary measures and MENQOL between the letrozole and placebo groups. The data indicate that continuation of aromatase inhibitor therapy after 5 years of prior treatment in the trial population was not associated with a deterioration of overall QOL.

Purpose: National guidelines encourage counseling high-risk women about pharmacologic breast cancer risk reduction. We evaluated the use of integrated health care data to identify and characterize breast cancer chemoprevention use. Chemoprevention included US Food and Drug Administration-approved use of tamoxifen and raloxifene and off-label use of aromatase inhibitors (AIs)., Patients and Methods: Using electronic medical and pharmacy records (EMRs) in the Kaiser Permanente Northern California health care system, we sampled cancer-free women age 35 to 69 years who used tamoxifen, raloxifene, exemestane, anastrozole, or letrozole from 2005 to 2013. Risk-benefit profiles were calculated for tamoxifen and raloxifene using published indices. The proportion of days covered was calculated from pharmacy records to assess adherence., Results: Among 90 chemoprevention users (confirmed with EMR review from a sample of 371 women), 74% used tamoxifen, 11% used raloxifene, and 13% used an AI. For tamoxifen and raloxifene users, the risk-benefit index indicated 23% of women had insufficient evidence that benefits would outweigh risks. For all agents, adherence decreased from an average proportion of days covered of 75% at 1 year to 67% at 5 years. Automated EMR searches identified breast cancer chemoprevention users with 60% positive predictive value overall and 75% for tamoxifen after post hoc modifications., Conclusion: Our study contributes to an emerging picture of breast cancer chemoprevention use in real-world settings, where evidence of net benefit is not uniform and nonadherence is common. Among breast cancer chemoprevention agents, our automated selection best performed for tamoxifen use. We also identified off-label use of AIs for chemoprevention, suggesting that expansion of risk-benefit indices to include AIs is warranted.

Purpose: To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older")., Methods: Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (<1 year); midpoint (1-3 years); and late discontinuation (>3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates., Results: Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p < 0.001), considering covariates, but cognition was not related to discontinuation in the other periods., Conclusions: Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

The aim of this study was to evaluate the mental health consumption among patients with early-stage breast cancer in two radiation oncology departments in two countries (USA and Italy). Data were extracted from the medical records of consecutive patients treated between 2014 and 2015 in two centers. Extracted data included patient's demographics, treatment, referral to psychological supportive care programs, and prescribed psychotropic drugs. Data from the two centers were compared using Student's t, Wilcoxon, Fisher's exact, and Jonckheere-Terpstra tests. Adjusted relative risks (RR) were estimated using Poisson regression. A total of 231 (Italy = 110, USA = 121) patients were included, with a mean age of 60 years. The crude rate of psychological supportive care visits was similar in the US versus the Italian cohort (28.9 vs. 21.8%, p = 0.23). The crude rate of prescribed psychotropic drug was higher in the US cohort versus Italian cohort (43.8 vs. 18.2%, p < 0.0001). These differences remained significant after adjusting for breast cancer subtype, stage, and treatment (RR 1.8, 95 CI 1.17-2.76). Between 20 and 30% of patients receive psychological supportive care during treatment for breast cancer. The use of psychotropic medication was higher in the US cohort than the cohort from Italy. The reasons for these differences might be related to social and cultural differences and the method of prescribing medication.

Purpose: To evaluate the association between functional status based on a geriatric assessment (GA) and outcomes of tolerance to treatment in patients with lung or head and neck cancer receiving radiation therapy (RT) or chemoradiation (CRT)., Methods and Materials: A prospective cohort study was conducted in patients aged ≥65 years with head and neck cancer or lung cancer undergoing curative intent RT or CRT. Pretreatment GA, health-related quality of life (HRQoL), and patient-reported outcomes (PRO) were obtained. Questionnaires were repeated biweekly during RT and at 6 weeks after treatment. Dysfunction was defined as scores <14 on the Instrumental Activities of Daily Living scale. Poor tolerance to treatment was defined by hospitalization, >3-day treatment delay, change in RT or CRT regimen, or death. Associations of dysfunction with tolerance to radiation therapy, HRQoL changes, and PRO ratings were evaluated., Results: Of the 50 patients accrued, 46 had evaluable data. Mean age was 72.5 years (range, 65-92 years). At baseline, 37% had dysfunction. Poor tolerance to RT or CRT occurred in 39%. There was no association between dysfunction and tolerance. Patients with dysfunction had lower baseline HRQoL scores. From baseline to end of RT, those with baseline dysfunction had less of a decline in Role Functioning (P=.01) and Global Health Score (P=.04) domains. However, from end of RT to 6-week follow-up, those with dysfunction were more likely to continue to drop in the Physical, Role Functioning, and Social domains (all P<.01). Dysfunction at baseline was also associated with higher severity of certain PROs., Conclusions: Pretreatment dysfunction was associated with continued decline and lack of recovery of HRQoL in this patient population. Larger studies could further elucidate the GA's predictive value., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Breast cancer patients aged 65+ ("older") vary in frailty status. We tested whether a deficits accumulation frailty index predicted long-term mortality., Methods: Older patients (n = 1280) with non-metastatic, invasive breast cancer were recruited from 78 Alliance sites from 2004 to 2011, with follow-up to 2015. Frailty categories (robust, pre-frail, and frail) were based on 35 baseline illness and function items. Cox proportional hazards and competing risk models were used to calculate all-cause and breast cancer-specific mortality for up to 7 years, respectively. Potential covariates included demographic, psychosocial, and clinical factors, diagnosis year, and care setting., Results: Patients were 65-91 years old. Most (76.6%) were robust; 18.3% were pre-frail, and 5.1% frail. Robust patients tended to receive more chemotherapy ± hormonal therapy (vs. hormonal) than pre-frail or frail patients (45% vs. 37 and 36%, p = 0.06), and had the highest adherence to hormonal therapy. The adjusted hazard ratios for all-cause mortality (n = 209 deaths) were 1.7 (95% CI 1.2-2.4) and 2.4 (95% CI 1.5-4.0) for pre-frail and frail versus robust women, respectively, with an absolute mortality difference of 23.5%. The adjusted hazard of breast cancer death (n-99) was 3.1 (95% CI 1.6-5.8) times higher for frail versus robust patients (absolute difference of 14%). Treatment differences did not account for the relationships between frailty and mortality., Conclusions: Most older breast cancer patients are robust and could consider chemotherapy where otherwise indicated. Patients who are frail or pre-frail have elevated long-term all-cause and breast cancer mortality. Frailty indices could be useful for treatment decision-making and care planning with older patients.

Purpose: The incidence of treatment-related toxicity for adjuvant chemotherapy in breast cancer is well documented in clinical trials. However, the effect of chemotherapy on functional outcomes in older patients is less well known. We identified a cohort of older women diagnosed with early stage breast cancer to examine the association between exposure to chemotherapy and a claims-based measure of function-related adverse events (FAE)., Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset, we identified women aged ≥66 diagnosed with stage I or II breast cancer from 2004 to 2011. FAE were defined as one or more claims suggestive of functional impairment within 24months following chemotherapy including claims for durable medical equipment and skilled care. Women who did not receive chemotherapy were weighted to reflect the covariate distribution of chemotherapy recipients using propensity score weighting for age, stage, baseline healthcare utilization, and comorbidities., Results: The cohort included 44,626 patients, 6892 (15%) received chemotherapy. 19% of the population experienced ≥1 FAE. After propensity weighting, chemotherapy was associated with a small increased risk of FAEs (HR 1.12, 95% confidence interval: 1.04, 1.20). Results were similar in patients 75years and older versus younger patients. In the chemotherapy group, the highest risk of FAE occurred in the first 3months, but persisted through follow-up., Conclusions: Exposure to chemotherapy was associated with a small increased risk of FAE which did not vary by age. These data can be used to inform treatment decision making for older patients with breast cancer who are eligible for adjuvant chemotherapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Tools to estimate survival, such as ePrognosis ( http://eprognosis.ucsf.edu/carey2.php ), were developed for general, not cancer, populations. In older patients with breast cancer, accurate overall survival estimates would facilitate discussions about adjuvant therapies., Methods: Secondary analyses were performed of data from two parallel breast cancer studies (CALGB/Alliance 49907/NCT000224102 and CALGB/Alliance 369901/NCT00068328). We included patients (n = 971) who were age 70 years and older with complete baseline quality of life data (194 from 49907; 777 from 369901). Estimated versus observed all-cause two-year mortality rates were compared. ePrognosis score was calculated based on age, sex, and daily function (derived from EORTC QLQ-C30). ePrognosis scores range from 0 to 10, with higher scores indicating worse prognosis based on mortality of community-dwelling elders and were categorized into three groups (0-2, 3-6, 7-10). Observed mortality rates were estimated using Kaplan-Meier methods., Results: Patient mean age was 75.8 years (range 70-91) and 73% had stage I-IIA disease. Most patients were classified by ePrognosis as good prognosis (n = 562, 58% 0-2) and few (n = 18, 2% 7-10) poor prognosis. Two-year observed mortality rates were significantly lower than ePrognosis estimates for patients scoring 0-2 (2% vs 5%, p = 0.001) and 3-6 (8% vs 12%, p = 0.01). The same trend was seen with scores of 7-10 (23% vs 36%, p = 0.25)., Conclusions: ePrognosis tool only modestly overestimates mortality rate in older breast cancer patients enrolled in two cooperative group studies. This tool, which estimates non-cancer mortality risk based on readily available clinical information may inform adjuvant therapy decisions but should be validated in non-clinical trial populations.

Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a proinflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating cells nonspecifically, often with adverse reactions. In accord with prior work, we show that several chemotherapeutic drugs induce senescence of primary murine and human cells. Using a transgenic mouse that permits tracking and eliminating senescent cells, we show that therapy-induced senescent (TIS) cells persist and contribute to local and systemic inflammation. Eliminating TIS cells reduced several short- and long-term effects of the drugs, including bone marrow suppression, cardiac dysfunction, cancer recurrence, and physical activity and strength. Consistent with our findings in mice, the risk of chemotherapy-induced fatigue was significantly greater in humans with increased expression of a senescence marker in T cells prior to chemotherapy. These findings suggest that senescent cells can cause certain chemotherapy side effects, providing a new target to reduce the toxicity of anticancer treatments., Significance: Many genotoxic chemotherapies have debilitating side effects and also induce cellular senescence in normal tissues. The senescent cells remain chronically present where they can promote local and systemic inflammation that causes or exacerbates many side effects of the chemotherapy. Cancer Discov; 7(2); 165-76. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 115., Competing Interests: All other authors declare no financial interests., (©2016 American Association for Cancer Research.)

Purpose: Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = 500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250)., Patients and Methods: Patients age ≥ 65 years with a solid tumor, fluent in English, and who were scheduled to receive a new chemotherapy regimen were recruited from eight institutions. Risk of chemotherapy toxicity was calculated (low, medium, or high risk) on the basis of the prediction model before the start of chemotherapy. Chemotherapy-related toxicity was captured (grade 3 [hospitalization indicated], grade 4 [life threatening], and grade 5 [treatment-related death]). Validation of the prediction model was performed by calculating the area under the receiver-operating characteristic curve., Results: The study sample (N = 250) had a mean age of 73 years (range, 65 to 94 [standard deviation, 5.8]). More than one half of patients (58%) experienced grade ≥ 3 toxicity. Risk of toxicity increased with increasing risk score (36.7% low, 62.4% medium, 70.2% high risk; P < .001). The area under the curve of the receiver-operating characteristic curve was 0.65 (95% CI, 0.58 to 0.71), which was not statistically different from the development cohort (0.72; 95% CI, 0.68 to 0.77; P = .09). There was no association between Karnofsky Performance Status and chemotherapy toxicity (P = .25)., Conclusion: This study externally validated a chemotherapy toxicity predictive model for older adults with cancer. This predictive model should be considered when discussing the risks and benefits of chemotherapy with older adults., (© 2016 by American Society of Clinical Oncology.)