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Background Chemotoxicity risk scores were developed to predict grade 3-5 chemotherapy toxicity in older women with early breast cancer. However, whether these toxicity risk scores are associated with clinically meaningful decline in patient health remains unknown. Methods In a prospective study of women aged 65 years and older with stage I-III breast cancer treated with chemotherapy, we assessed chemotoxicity risk using the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score (categorized as low, intermediate, and high). We measured patient health status before (T1) and after (T2) chemotherapy using a clinical frailty index (Deficit Accumulation Index, categorized as robust, prefrail, and frail). The population of interest was robust women at T1. The primary outcome was decline in health status after chemotherapy, defined as a decline in Deficit Accumulation Index from robust at T1 to prefrail or frail at T2. Multivariable logistic regression was used to examine the association between T1 CARG-BC score and decline in health status, adjusted for sociodemographic and clinical characteristics. Results Of the 348 robust women at T1, 83 (24%) experienced declining health status after chemotherapy, of whom 63% had intermediate or high CARG-BC scores. After adjusting for sociodemographic and clinical characteristics, women with intermediate (odds ratio = 3.14, 95% confidence interval = 1.60 to 6.14, P Conclusions In this cohort of older women with early breast cancer, higher CARG-BC scores before chemotherapy were associated with decline in health status after chemotherapy independent of sociodemographic and clinical risk factors.

PURPOSE To examine longitudinal relationships between levels of C-reactive protein (CRP) and cognition in older breast cancer survivors and noncancer controls. METHODS English-speaking women age ≥ 60 years, newly diagnosed with primary breast cancer (stage 0-III), and frequency-matched controls were enrolled from September 2010 to March 2020; women with dementia, neurologic disorders, and other cancers were excluded. Assessments occurred presystemic therapy/enrollment and at annual visits up to 60 months. Cognition was measured using the Functional Assessment of Cancer Therapy-Cognitive Function and neuropsychological testing. Mixed linear effect models tested for survivor-control differences in natural log (ln)-transformed CRP at each visit. Random effect–lagged fluctuation models tested directional effects of ln-CRP on subsequent cognition. All models controlled for age, race, study site, cognitive reserve, obesity, and comorbidities; secondary analyses evaluated if depression or anxiety affected results. RESULTS There were 400 survivors and 329 controls with CRP specimens and follow-up data (average age of 67.7 years; range, 60-90 years). The majority of survivors had stage I (60.9%), estrogen receptor–positive (87.6%) tumors. Survivors had significantly higher adjusted mean ln-CRP than controls at baseline and 12-, 24-, and 60-month visits (all P < .05). Higher adjusted ln-CRP predicted lower participant-reported cognition on subsequent visits among survivors, but not controls ( P interaction = .008); effects were unchanged by depression or anxiety. Overall, survivors had adjusted Functional Assessment of Cancer Therapy-Cognitive Function scores that were 9.5 and 14.2 points lower than controls at CRP levels of 3.0 and 10.0 mg/L. Survivors had poorer neuropsychological test performance ( v controls), with significant interactions with CRP only for the Trails B test. CONCLUSION Longitudinal relationships between CRP and cognition in older breast cancer survivors suggest that chronic inflammation may play a role in development of cognitive problems. CRP testing could be clinically useful in survivorship care.

Preeclampsia (PE) is a condition that poses a significant risk of maternal mortality and multiple organ failure during pregnancy. Early prediction of PE can enable timely surveillance and interventions, such as low-dose aspirin administration. In this study, conducted at Stanford Health Care, we examined a cohort of 60 pregnant women and collected 478 urine samples between gestational weeks 8 and 20 for comprehensive metabolomic profiling. By employing liquid chromatography mass spectrometry (LCMS/MS), we identified the structures of seven out of 26 metabolomics biomarkers detected. Utilizing the XGBoost algorithm, we developed a predictive model based on these seven metabolomics biomarkers to identify individuals at risk of developing PE. The performance of the model was evaluated using 10-fold cross-validation, yielding an area under the receiver operating characteristic curve of 0.856. Our findings suggest that measuring urinary metabolomics biomarkers offers a noninvasive approach to assess the risk of PE prior to its onset.

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

Background Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients. Methods We enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aβ, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery. Results There were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aβ levels than non-carriers (preoperative median CSF Aβ [median absolute deviation], APOE4 305 pg ml−1 [65] vs 378 pg ml−1 [38], respectively; P=0.001). Controlling for age, APOE4 carriers had significantly greater preoperative functional connectivity than non-carriers between several brain regions implicated in Alzheimer's disease, including between the left posterior cingulate cortex and left angular gyrus (β [95% confidence interval, CI], 0.218 [0.137–0.230]; PFWE=0.016). APOE4 carriers, but not non-carriers, experienced significant connectivity decreases from before to 6 weeks after surgery between several brain regions including between the left posterior cingulate cortex and left angular gyrus (β [95% CI], –0.196 [–0.256 to –0.136]; PFWE=0.001). Most preoperative and postoperative functional connectivity differences did not change after controlling for preoperative CSF Aβ levels. Conclusions Postoperative change trajectories for cognition and CSF Aβ, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aβ-independent mechanisms.

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.

PURPOSE: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. METHODS: Individual-level data was pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36-months after. Cognitive performance was assessed with objective (working memory, processing speed and executive functions) and subjective tests and physical, emotional and functional well-being was also assessed. RESULTS: One hundred and sixty-seven (M age = 67.3 years) women, with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36-months. Measures of well-being improved from prior to systemic therapy to 12-months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. CONCLUSION: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.

Association between the CARG-BC score and clinical decline after adjuvant chemotherapy in fit older adults with breast cancer: Results from the Hurria Older PatiEnts (HOPE) Prospective Study Background: We previously developed and validated a risk prediction model for grade 3-5 chemotherapy toxicity in patients age ≥65 with early breast cancer, known as the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score. The CARG-BC score is calculated by combining eight clinical variables that classify patients as low, intermediate, and high risk for grade 3-5 chemotherapy toxicity. However, whether this score can also identify individuals most likely to experience a clinical decline after chemotherapy remains unknown. Here, we evaluated the association between the CARG-BC score and decline in health status. Methods: This is a pre-specified secondary analysis of the Hurria Older PatiEnts (HOPE) with Breast Cancer Study (NCT01472094). This multicenter, prospective cohort study gathered biological and clinical data from women ≥65 with stage I-III breast cancer scheduled to receive neo/adjuvant chemotherapy. Health status was measured pre- (≤14 days) and post-chemotherapy (≤30 days) using a Deficit Accumulation Index (DAI), derived from geriatric assessment data (Cohen et al Cancer 2017). The DAI categorized patients as robust (0.0< 0.2), prefrail (0.2< 0.35), or frail (≥0.35). Baseline clinical characteristics, blood biomarkers of inflammation (interleukin-6 [IL-6] and C-reactive protein [CRP]), and CARG-BC scores (classified as low [0-5], intermediate [6-11] or high [≥12]) were collected pre-chemotherapy. The population of interest was older women who were clinically fit (defined as robust per the DAI) pre-chemotherapy. The primary outcome was chemotherapy-induced decline in health status, a dichotomized (yes/no) variable defined as a decline in DAI from robust pre-chemotherapy to pre-frail or frail post-chemotherapy. Multivariable logistic regression was used to examine the association between baseline CARG-BC score and chemotherapy-induced decline in health status. Results: Of 392 women included in this analysis, 316 (80.6%) were clinically fit based on DAI assessment pre-chemotherapy. The median age was 70 (range 65-86), 61.7% had stage II or III disease, 31% had HR+/HER2+ disease, 22% had HR-/HER2- disease, 36% received an anthracycline, and 74% received prophylactic WBC growth factors. At baseline, 38.7% had low, 53.4% had intermediate, and 7.9% had high CARG-BC scores. Among the 316 clinically fit patients, 80 (25.3%) experienced a decline in health status at the end of chemotherapy. In univariate analysis, we observed that patients with high IL-6 (odds ratio [OR]=2.24, 95% CI: 1.32-3.79, p=0.003), high CRP (OR=1.84, 95%: CI 1.10-3.09, p=0.02), and intermediate (OR=3.29, 95% CI 1.72-6.29, p< 0.001) or high (OR=6.29, 95% CI 2.36-16.71, p< 0.001) CARG-BC scores were more likely to experience chemotherapy-induced decline in health status. After adjusting for IL-6 and CRP, patients with both intermediate (OR=3.25, 95% CI 1.68-6.27, p< 0.001) and high (OR=5.17, 95% CI 1.90-14.02, p=0.001) CARG-BC scores had significantly higher odds of experiencing chemotherapy-induced clinical decline as compared to patients with low CARG-BC scores. Conclusions: In this cohort of older women with early breast cancer who were clinically fit pre-chemotherapy, 25% experienced a decline in health status after neo/adjuvant chemotherapy. Women with an intermediate/high CARG-BC score prior to chemotherapy had 3-5-fold increased odds of experiencing chemotherapy-induced decline in health status independent of baseline clinical characteristics and biomarkers of inflammation. These findings may be useful to clinicians for predicting individual probability of chemotherapy-induced clinical decline and informing treatment decisions in older adults with early breast cancer. Table 1. Univariate and multivariable association of the CARG-BC score with chemotherapy-induced decline in health status. Multivariable analysis adjusted for baseline demographic, clinical, and inflammatory levels (IL-6 and CRP); *CARG-BC score is calculated using 8 independent predictors (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). The total CARG-BC risk score is the sum of each point derived from these 8 predictors. Each patient’s total CARG-BC score can then be classified into three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). Citation Format: Jingran Ji, Canlan Sun, Hyman B. Muss, Harvey J. Cohen, Mina S. Sedrak. PD6-01 Association between the CARG-BC score and clinical decline after adjuvant chemotherapy in fit older adults with breast cancer: Results from the Hurria Older PatiEnts (HOPE) Prospective Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD6-01.

Purpose: Cancer-related cognitive problems may result from peripheral inflammation effects on the brain. We tested whether differences in cognitive performance between breast cancer survivors and non-cancer controls was explained by elevated inflammatory cytokines. Methods: We enrolled women >60 years, newly diagnosed with primary breast cancer (stage 0-III) (n=400) and frequency-matched non-cancer controls (n=329) from six national centers from 2010- 2020, with blood collection beginning in 2016. Baseline assessments occurred pre-systemic therapy (or enrollment for controls) with annual follow-up to 60-months. The primary outcome was the score on neurocognitive tests of the attention, processing speed and executive function (APE) domain. Plasma levels of IL-6, IL-10, and TNF-alpha were determined using multiplex testing and mixed linear models compared results for each marker across all timepoints by survivor/control group, adjusting for age, race, WRAT scores, recruitment site, comorbidities, and BMI. Multi-level mediation analyses tested the simultaneous direct effects of survivor/control group on cognition and indirect effects of group on each immune marker and the effect of the marker on cognition, controlling for covariates. Results: Participants had an average age of 67.7 years (range: 60-90). Most survivors had stage I (60.9%) estrogen-receptor positive (87.6%) tumors. Survivors had significantly higher adjusted IL-6 levels than controls at baseline, 12-, 24- and 60-months (p=< 0.001 to 0.014), but there were no differences for other markers. Survivors had lower adjusted APE scores than controls, and this effect was due to the indirect effects of being a survivor vs. control on IL-6 (p=0.047). Conclusion: Cancer and its treatments were related to poorer attention, processing speed, and executive function compared to non-cancer frequency matched controls, and this difference was partially explained by elevated IL-6. Citation Format: Jeanne S. Mandelblatt, Brent J. Small, Xingtao Zhou, Zev M. Nakamura, Harvey J. Cohen, Tim A. Ahles, Jaeil Ahn, Traci N. Bethea, Martine Extermann, Heather S.L. Jim, Brenna C. McDonald, Sunita K. Patel, Kelly Rentscher, James Root, Andrew J. Saykin, Kathleen Van Dyk, Wanting Zhai, Elizabeth C. Breen, Judith E. Carroll. Differences in attention, processing speed, and executive function in older breast cancer survivors compared to controls is partially explained by plasma IL-6: The Thinking and Living with Cancer (TLC) Study [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A012.

Cancer and its treatments are thought to increase risk for accelerated aging in survivors, and biological aging may be a key mechanism; however, no research to date has examined epigenetic markers of aging in long-term breast cancer survivors. We used data from the Thinking and Living with Cancer (TLC) study to examine whether older breast cancer survivors have accelerated epigenetic aging compared to non-cancer controls several years after treatment completion and whether epigenetic aging related to cognitive and physical function. Non-metastatic breast cancer survivors ages 62–84 years (n=89) and frequency-matched controls (n=101) provided two blood samples between 24- and 60-months post-diagnosis. DNA methylation profiling (Illumina Infinium EPIC array) derived epigenetic aging measures: Horvath, Hannum, PhenoAge, GrimAge, and Dunedin Pace of Aging Methylation. Participants completed neuropsychological testing and questionnaires to assess cognitive and physical function at each visit. Mixed-effects models adjusted for chronological age and comorbidities and applied false discovery rate correction for multiple testing. Survivors were 1.04–2.22 years older biologically than controls at the first blood sample based on Horvath, Hannum, and GrimAge measures (corrected ps=.025, .025, and .058, respectively), with marginal differences for Dunedin Pace of Aging (corrected p=.096); however, survivors and controls showed similar changes in epigenetic aging over time. Exposure to prior chemotherapy (with or without hormonal therapy; n=29) was associated with an epigenetic age 1.97–2.71 years older than controls (corrected ps=.005 to .065). Among survivors who received chemotherapy, an older Hannum epigenetic age was associated with poorer self-reported cognition relative to controls (coeff=-0.64, uncorrected p=.047; n.s. after correction). Older breast cancer survivors, particularly those receiving chemotherapy, showed an accelerated epigenetic aging profile compared to their peers without cancer at 24 months or more post-diagnosis, following the completion of active therapy. This study also provides preliminary evidence that survivors who received chemotherapy may be at increased risk for poorer age-related survivorship outcomes. Citation Format: Kelly E. Rentscher, Wanting Zhai, Brent J. Small, Jaeil Ahn, Tim A. Ahles, Traci N. Bethea, Elizabeth C. Breen, Harvey J. Cohen, Martine Extermann, Deena M.A. Graham, Paul B. Jacobsen, Heather S.L. Jim, Brenna C. McDonald, Zev M. Nakamura, Sunita K. Patel, James C. Root, Andrew J. Saykin, Danielle B. Tometich, Kathleen M. Van Dyk, Xingtao Zhou, Jeanne S. Mandelblatt, Judith E. Carroll. Long-term epigenetic aging in older breast cancer survivors and non-cancer controls: Preliminary findings from the Thinking and Living with Cancer (TLC) Stud [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B018.

Introduction: While some cancer survivors experience minimal lasting effects of diagnosis and treatment, others report persistent decrements in physical and cognitive function. These changes may represent aging beyond that expected for the chronological age (i.e., “accelerated aging”). Racial minority groups often have an accelerated aging phenotype even before cancer diagnosis, partly due to chronic stress and other multi-level factors that affect aging and the ability to repair physiologic damage, leaving them more vulnerable to poor survivorship outcomes. However, we know little about physical and cognitive aging in this group and few studies have collected objective measures of physical and cognitive aging in minority cancer survivors. Methods: We examined changes in physical and cognitive function across 60 months of follow-up among Black and White survivors in the Thinking and Living with Cancer Study (TLC). TLC is an ongoing prospective multi-site cohort study recruiting non-metastatic breast cancer survivors aged ≥60 years. Participants completed questionnaires and objective assessments prior to systemic therapy with annual follow-up for up to 60 months. Physical function was measured using the timed up and go test (TUG); cognitive function was measured with Z scores on 11 neuropsychological tests for two domains: learning and memory (LM) and attention, processing, and executive function (APE). Mixed linear regression models predicting TUG, APE, or LM adjusted for age, study site, time, and cognitive reserve using the Wide Range Achievement Test (WRAT). Results: Black and White survivors in TLC were similar in age, education, comorbidities, and year of enrollment (p>0.14), but differed by study site (p Citation Format: Traci N. Bethea, Wanting Zhai, Xingtao Zhou, Tim A. Ahles, Jaeil Ahn, Harvey J. Cohen, Asma A. Dilawari, Deena Graham, Heather Jim, Brenna C. McDonald, Zev M. Nakamura, Sunita K. Patel, Kelly E. Rentscher, James C. Root, Andrew J. Saykin, Brent J. Small, Kathleen Van Dyk, Jeanne S. Mandelblatt, Judith E. Carroll. Black-White differences in physical and cognitive aging among older breast cancer survivors in the Thinking and Living with Cancer Study [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B111.

PurposeOlder cancer survivors required medical care during the COVID-19 pandemic despite infection risks, but there are limited data on medical care in this age group. Methods. We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors ages 60-98 from five US regions (n=321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included self-reported interruptions in ability to see doctors, receive treatment or supportive therapies, or fill prescriptions. Logistic regression models evaluated bivariate and multivariate associations between care disruptions and education, medical, psychosocial and COVID-19-related factors. Multivariate models included age, county COVID-19 rates, comorbidity and post-diagnosis time. Results. There was a high response rate (n=262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were significantly higher with more education (OR 1.23 per one-year increase, 95% CI 1.09-1.39, p =0.001) and greater depression (OR 1.04 per one-point increase in CES-D score, CI 1.003-1.08, p=0.033); tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99 per one-point increase, p=0.012). There was a trend for associations between disruptions and comorbidity (unadjusted OR 1.13 per 1 added comorbidity, 95% CI 0.99-1.29, p=0.07). Adjusting for covariates, only higher education (p=0.001) and tangible social support (p=0.006) remained significantly associated with having care disruptions. Conclusions. Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.

Introduction Treatment burden is emerging as an important patient-centered outcome for older adults with cancer who concurrently manage geriatric conditions. Our objective was to evaluate the contribution of geriatric conditions to treatment burden in older adults with non-muscle invasive bladder cancer (NMIBC). Methods We identified 73,395 Medicare beneficiaries age 66+ diagnosed with NMIBC (Stage Results At baseline, 64% had multimorbidity and median 3 conditions (IQR 0–5). Prevalence of other geriatric conditions ranged from 5.9%–15.2%. Adjusted mean health system contact was 8.9 days (95% CI 8.6–9.2). Multimorbidity had the largest effect size (adjusted mean 11.8 contact days (95% CI 8.3–8.8)). Each additional chronic condition conferred a 13% increased average number of health system contact (adjusted IRR 1.132, 95% CI 1.129–1.135). Regardless of number of chronic conditions, rural patients consistently had more treatment burden than urban counterparts. Discussion In this population-based cohort of older NMIBC patients, multimorbidity and rurality were strongly associated with treatment burden in the year following NMIBC diagnosis. These findings highlight the need for interventions that reduce treatment burden due to geriatric conditions among the growing population of older adults with cancer, particularly in rural areas.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

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 The coronavirus disease 2019 (COVID‐19) pandemic has had wide‐ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic. Methods The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web‐based or telephone COVID‐19 survey, between May 27 and September 11, 2020. Mixed‐effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies–Depression [CES‐D] scale) from before to during the pandemic in survivors versus controls and to test survivor‐control differences in the associations between changes in loneliness and changes in mental health, including depression (CES‐D, excluding the loneliness item), anxiety (the State‐Trait Anxiety Inventory), and perceived stress (the Perceived Stress Scale). Models were adjusted for age, race, county COVID‐19 death rates, and time between assessments. Results Loneliness increased from before to during the pandemic (0.211; P = .001), with no survivor‐control differences. Increased loneliness was associated with worsening depression (3.958; P < .001) and anxiety (3.242; P < .001) symptoms and higher stress (1.172; P < .001) during the pandemic, also with no survivor‐control differences. Conclusions Cancer survivors reported changes in loneliness and mental health similar to those reported by women without cancer. However, both groups reported increased loneliness from before to during the pandemic that was related to worsening mental health, suggesting that screening for loneliness during medical care interactions will be important for identifying all older women at risk for adverse mental health effects of the pandemic., Older breast cancer survivors and matched noncancer controls experienced similar increases in loneliness from before to during the COVID‐19 pandemic. Women who reported increased loneliness also experienced worsening depression and anxiety symptoms and higher stress during the pandemic.

PURPOSE Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer. METHODS Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated. RESULTS In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively ( P < .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity ( P < .01). CONCLUSION The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.

Background We evaluated deficit accumulation and how deficits affected cognition and physical activity among breast cancer survivors and non-cancer controls. Methods Newly diagnosed nonmetastatic survivors (n = 353) and matched non-cancer controls (n = 355) ages 60-98 years without neurological impairments were assessed presystemic therapy (or at enrollment for controls) from August 2010 to December 2016 and followed for 36 months. Scores on a 42-item index were analyzed in growth-mixture models to determine deficit accumulation trajectories separately and combined for survivors and controls. Multilevel models tested associations between trajectory and cognition (FACT-Cog and neuropsychological tests) and physical activity (IPAQ-SF) for survivors and controls. Results Deficit accumulation scores were in the robust range, but survivors had higher scores (95% confidence intervals [CI]) than controls at 36 months (0.18, 95% CI = 0.16 to 0.19, vs 0.16, 95% CI = 0.14 to 0.17; P = .001), and averages included diverse deficit trajectories. Survivors who were robust but became frailer (8.8%) had similar baseline characteristics to those remaining robust (76.2%) but experienced a 9.6-point decline self-reported cognition (decline of 9.6 vs 3.2 points; P = .04) and a 769 MET minutes per week decline in physical activity (P < .001). Survivors who started and remained prefrail (15.0%) had self-reported and objective cognitive problems. At baseline, frail controls (9.5%) differed from robust controls (83.7%) on deficits and self-reported cognition (P < .001). Within combined trajectories, frail survivors had more sleep disturbances than frail controls (48.6% [SD = 17.4%] vs 25.0% [SD = 8.2%]; P = .05). Conclusions Most survivors and controls remained robust, and there were similar proportions on a frail trajectory. However, there were differences in deficit patterns between survivors and controls. Survivor deficit accumulation trajectory was associated with patient-reported outcomes. Additional research is needed to understand how breast cancer and its treatments affect deficit accumulation.

Background: Pregnancy triggers longitudinal metabolic alterations in women to allow precisely-programmed fetal growth. Comprehensive characterization of such a “metabolic clock” of pregnancy may provide a molecular reference in relation to studies of adverse pregnancy outcomes. However, a high-resolution temporal profile of metabolites along a healthy pregnancy remains to be defined.Methods: Two independent, normal pregnancy cohorts with high-density weekly urine sampling (discovery: 478 samples from 19 subjects at California; validation: 171 samples from 10 subjects at Alabama) were studied. Urine samples were profiled by liquid chromatography-mass spectrometry (LC-MS) for untargeted metabolomics, which was applied for gestational age dating and prediction of time to delivery.Results: 5,473 urinary metabolic features were identified. Partial least-squares discriminant analysis on features with robust signals (n = 1,716) revealed that the samples were distributed on the basis of the first two principal components according to their gestational age. Pathways of bile secretion, steroid hormone biosynthesis, pantohenate, and CoA biosynthesis, benzoate degradation, and phenylpropanoid biosynthesis were significantly regulated, which was collectively applied to discover and validate a predictive model that accurately captures the chronology of pregnancy. With six urine metabolites (acetylcholine, estriol-3-glucuronide, dehydroepiandrosterone sulfate, α-lactose, hydroxyexanoy-carnitine, and l-carnitine), models were constructed based on gradient-boosting decision trees to date gestational age in high accordance with ultrasound results, and to accurately predict time to delivery.Conclusion: Our study characterizes the weekly baseline profile of the human pregnancy metabolome, which provides a high-resolution molecular reference for future studies of adverse pregnancy outcomes.