A phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects.

BACKGROUND: Cognitive difficulties have been described after chemotherapy for breast cancer, but there is no standard of care to improve cognitive outcomes in these patients. This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during chemotherapy for breast cancer. METHODS: Patients with stage I-III breast cancer, scheduled for neo/adjuvant chemotherapy, completed a cognitive battery prior to and 4 weeks after completing chemotherapy. Memantine (10 mg BID) was administered concurrent with chemotherapy. Our primary cognitive outcome was visual working memory assessed by the Delayed Matching to Sample test. We used the Brief Medication Questionnaire to assess acceptability. RESULTS: Of 126 patients approached, 56 (44%) enrolled. Forty-five (80%) received ≥1 dose of memantine and completed pre-post assessments. Seventy-six percent reported taking ≥90% of scheduled doses. Participants were mean age of 56, 77% White, and 57% had stage I disease. Sixty-four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%-91% across objective cognitive domain composite measures. Sixty-six percent self-reported stable or improved cognitive symptoms. There were seven greater than or equal to grade 3 adverse events; two were possibly related to memantine. Only 5% reported that taking memantine was a disruption to their lives. CONCLUSIONS: Memantine was well-tolerated and consistently taken by a large majority of patients receiving breast cancer chemotherapy. The majority demonstrated stable or improved cognition from pre- to post-assessment. Randomized trials are needed to determine memantine's efficacy to ameliorate cognitive loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT04033419.

A biomarker of aging, p16, predicts peripheral neuropathy in women receiving adjuvant taxanes for breast cancer.

Identifying patients at higher risk of chemotherapy-induced peripheral neuropathy (CIPN) is a major unmet need given its high incidence, persistence, and detrimental effect on quality of life. We determined if the expression of p16, a biomarker of aging and cellular senescence, predicts CIPN in a prospective, multi-center study of 152 participants enrolled between 2014 and 2018. Any women with newly diagnosed Stage I-III breast cancer scheduled to receive taxane-containing chemotherapy was eligible. The primary outcome was development of grade 2 or higher CIPN during chemotherapy graded by the clinician before each chemotherapy cycle (NCI-CTCAE v5 criteria). We measured p16 expression in peripheral blood T cells by qPCR before and at the end of chemotherapy. A multivariate model identified risk factors for CIPN and included taxane regimen type, p16Age Gap, a measure of discordance between chronological age and p16 expression, and p16 expression before chemotherapy. Participants with higher p16Age Gap-higher chronological age but lower p16 expression prior to chemotherapy - were at the highest risk. In addition, higher levels of p16 before treatment, regardless of patient age, conferred an increased risk of CIPN. Incidence of CIPN positively correlated with chemotherapy-induced increase in p16 expression, with the largest increase seen in participants with the lowest p16 expression before treatment. We have shown that p16 expression levels before treatment can identify patients at high risk for taxane-induced CIPN. If confirmed, p16 might help guide chemotherapy selection in early breast cancer.

Weathering the Storm: Managing Older Adults With Breast Cancer Amid COVID-19 and Beyond.

Caring for older patients with breast cancer presents unique clinical considerations because of preexisting and competing comorbidity, the potential for treatment-related toxicity, and the consequent impact on functional status. In the context of the COVID-19 pandemic, treatment decision making for older patients is especially challenging and encourages us to refocus our treatment priorities. While we work to avoid treatment delays and maintain therapeutic benefit, we also need to minimize the risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, myelosuppression, general chemotherapy toxicity, and functional decline. Herein, we propose multidisciplinary care considerations for the aging patient with breast cancer, with the goal to promote a team-based, multidisciplinary treatment approach during the COVID-19 pandemic and beyond. These considerations remain relevant as we navigate the "new normal" for the approximately 30% of breast cancer patients aged 70 years and older who are diagnosed in the United States annually and for the thousands of older patients living with recurrent and/or metastatic disease.

Patient-reported symptom severity, interference with daily activities, and adverse events in older and younger women receiving chemotherapy for early breast cancer.

BACKGROUND: To the authors' knowledge, it is unknown whether patient-reported symptom severity and symptom interference with daily activities differ between younger (aged <65 years) and older (aged ≥65 years) women receiving similar chemotherapy regimens for early breast cancer (EBC). METHODS: Study participants rated 17 side effects of chemotherapy regimens currently in use in clinical practice (2014-2019). RESULTS: Of 284 women with EBC (stage I-III), approximately 57% were aged <65 years and 43% were aged ≥65 years. For anthracycline-based regimens, a higher percentage of younger women reported moderate, severe, or very severe (MSVS) hot flashes (49% vs 18%) (P < .001). For nonanthracycline regimens, a higher percentage of younger women reported MSVS hot flashes (38% vs 19%) (P = .009) and a lower percentage reported MSVS arthralgia (28% vs 49%) (P = .005). With regard to symptom interference with daily activities, a higher percentage of younger women being treated with anthracycline-based regimens reported MSVS hot flashes (32% vs 7%) (P = .001) and myalgia (38% vs 18%) (P = .02). For nonanthracycline chemotherapy, a higher percentage of younger women reported MSVS interference for hot flashes (26% vs 9%) (P = .006) and lower percentages reported abdominal pain (13% vs 28%) (P = .02). Overall, there were no significant differences noted among younger versus older patients with regard to hospitalizations (19% vs 12%; P = .19), dose reductions (34% vs 31%; P = .50), dose delays (22% vs 25%; P = .59), or early treatment discontinuation (16% vs 16%; P = .9546). CONCLUSIONS: Older and younger women with EBC who were treated with identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events. LAY SUMMARY: In this study, women receiving chemotherapy for early breast cancer rated the severity of 17 symptoms and symptom interference with their activities of daily living. Older (aged ≥65 years) and younger (aged <65 years) women who received identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events.

Congruence of patient- and clinician-reported toxicity in women receiving chemotherapy for early breast cancer.

BACKGROUND: The National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, collected alongside the clinician-reported Common Terminology Criteria for Adverse Events, enables comparisons of patient and clinician reports on treatment toxicity. METHODS: In a multisite study of women receiving chemotherapy for early-stage breast cancer, symptom reports were collected on the same day from patients and their clinicians for 17 symptoms; their data were not shared with each other. The proportions of moderate, severe, or very severe patient-reported symptom severity were compared with the proportions of clinician-rated grade 2, 3, or 4 toxicity. Patient-clinician agreement was assessed via κ statistics. Chi-square tests investigated whether patient characteristics were associated with patient-clinician agreement. RESULTS: Among 267 women, the median age was 58 years (range, 24-83 years), and 26% were nonwhite. There was moderate scoring agreement (κ = 0.413-0.570) for 53% of symptoms, fair agreement for 41% (κ = 0.220-0.378), and slight agreement for 6% (κ = 0.188). For example, patient-reported and clinician-rated percentages were 22% and 8% for severe or very severe fatigue, 41% and 46% for moderate fatigue, 32% and 39% for mild fatigue, and 6% and 7% for none. Clinician severity scores were lower for nonwhite patients in comparison with white patients for peripheral neuropathy, nausea, arthralgia, and dyspnea. CONCLUSIONS: Although clinician reporting of symptoms is common practice in oncology, there is suboptimal agreement with the gold standard of patient self-reporting. These data provide further evidence supporting the integration of patient-reported outcomes into oncological clinical research and clinical practice to improve monitoring of symptoms as well as timely interventions for symptoms.

Is "Geriatric" Assessment Just for Older Patients?

Geriatric assessment (GA) is used in oncology to identify deficits in older patients with cancer that may affect treatment choice. We examine GA in 550 patients with early breast cancer, including both younger (<65 years) and older women (aged 65 years or older), to assess the potential value of this tool in younger, presumed "healthier" patients. Although older women have more GA-identified deficits overall, younger patients are more anxious. Suboptimal physical function was problematic across the age spectrum. GA domains can identify major deficits in younger patients beyond those likely to be uncovered in routine investigation.

A Randomized Trial of Real-Time Geriatric Assessment Reporting in Nonelectively Hospitalized Older Adults with Cancer.

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.

Effects of Breast Cancer Adjuvant Chemotherapy Regimens on Expression of the Aging Biomarker, p16INK4a.

BACKGROUND: Although chemotherapy saves lives, increasing evidence shows that chemotherapy accelerates aging. We previously demonstrated that mRNA expression of p16INK4a , a biomarker of senescence and molecular aging, increased early and dramatically after beginning adjuvant anthracycline-based regimens in early stage breast cancer patients. Here, we determined if changes in p16INK4a expression vary by chemotherapy regimen among early stage breast cancer patients. METHODS: We conducted a study of stage I-III breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. p16INK4a expression was analyzed prechemotherapy and postchemotherapy (median 6.2 months after the last chemotherapy) in peripheral blood T lymphocytes. Chemotherapy-induced change in p16INK4a expression was compared among regimens. All statistical tests were 2-sided. RESULTS: In 146 women, chemotherapy was associated with a statistically significant increase in p16INK4a expression (accelerated aging of 17 years; P < .001). Anthracycline-based regimens were associated with the largest increases (accelerated aging of 23 to 26 years; P ≤ .008). Nonanthracycline-based regimens demonstrated a much smaller increase (accelerated aging of 9 to 11 years; P ≤ .15). In addition to the type of chemotherapy regimen, baseline p16INK4a levels, but not chronologic age or race, were also associated with the magnitude of increases in p16INK4a . Patients with lower p16INK4a levels at baseline were more likely to experience larger increases. CONCLUSIONS: Our findings suggest that the aging effects of chemotherapy may be influenced by both chemotherapy type and the patient's baseline p16INK4a level. Measurement of p16INK4a expression is not currently available in the clinic, but nonanthracycline regimens offering similar efficacy as anthracycline regimens might be favored.

Patient-reported and clinician-reported chemotherapy-induced peripheral neuropathy in patients with early breast cancer: Current clinical practice.

BACKGROUND: In the current study, the authors investigated the incidence of moderate to severe chemotherapy-induced peripheral neuropathy (CIPN) for chemotherapy regimens commonly used in current clinical practice for the treatment of patients with early breast cancer. Patient-reported and clinician-assessed CIPN severity scores were compared, and risk factors for CIPN severity were identified. METHODS: Patients completed a Patient-Reported Symptom Monitoring form and oncologists completed a Common Terminology Criteria for Adverse Events form. CIPN reports were collected prospectively during regularly scheduled infusion visits throughout the duration of chemotherapy. RESULTS: The sample included 184 women with a mean age of 55 years; approximately 73% were white. The 4 chemotherapy regimens used were doxorubicin and cyclophosphamide plus paclitaxel (60 patients); docetaxel and cyclophosphamide (50 patients); docetaxel, carboplatin, and anti-human epidermal growth factor receptor 2 (HER2) (24 patients); and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin (18 patients). All patients treated with doxorubicin and cyclophosphamide plus paclitaxel and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin received paclitaxel; all patients treated with docetaxel and cyclophosphamide and docetaxel, carboplatin, and anti-HER2 received docetaxel. The chemotherapy dose was reduced in 52 patients (28%); in 15 patients (29%), this reduction was due to CIPN. Chemotherapy was discontinued in 26 patients (14%), 8 because of CIPN. Agreement between patient-reported and clinician-assessed CIPN severity scores was minimal (weighted Cohen kappa, P = .34). Patient-reported moderate to severe CIPN was higher for paclitaxel (50%) compared with docetaxel (17.7%) (P < .001). Pretreatment arthritis and/or rheumatism (relative risk [RR], 1.58; 95% CI, 1.06-2.35 [P = .023]) and regimens containing paclitaxel (RR, 2.88; 95% CI, 1.72-4.83 [P < .0001]) were associated with higher CIPN severity. Being married (RR, 0.57; 95% CI, 0.37-0.887 [P = .01]) was found to be associated with lower CIPN severity. CONCLUSIONS: The discrepancy between patient-reported and clinician-assessed CIPN underscores the need for both patient and clinician perspectives regarding this common, dose-limiting, and potentially disabling side effect of chemotherapy.

Patient-Reported Toxicities During Chemotherapy Regimens in Current Clinical Practice for Early Breast Cancer.

BACKGROUND: This study explores the incidence of patient-reported major toxicity-symptoms rated "moderate," "severe," or "very severe"-for chemotherapy regimens commonly used in early breast cancer. PATIENTS AND METHODS: Female patients aged 21 years or older completed a validated Patient-Reported Symptom Monitoring instrument and rated 17 symptoms throughout adjuvant or neoadjuvant chemotherapy. Fisher's exact tests compared differences in percentages in symptom ratings, and general linear regression was used to model the incidence of patient-reported major toxicity. RESULTS: In 152 patients, the mean age was 54 years (range, 24-77), and 112 (74%) were white; 51% received an anthracycline-based regimen. The proportion of patients rating fatigue, constipation, myalgia, diarrhea, nausea, peripheral neuropathy, and swelling of arms or legs as a major toxicity at any time during chemotherapy varied significantly among four chemotherapy regimens (p < .05). The mean (SD) number of symptoms rated major toxicities was 6.3 (3.6) for anthracycline-based and 4.4 (3.5) for non-anthracycline-based regimens (p = .001; possible range, 0-17 symptoms). Baseline higher body mass index (p = .03), patient-reported Karnofsky performance status ≤80 (p = .0003), and anthracycline-based regimens (p = .0003) were associated with greater total number of symptoms rated major toxicities (alternative model: chemotherapy duration, p < .0001). Twenty-six percent of dose reductions (26 of 40), 75% of hospitalizations (15 of 20), and 94% of treatment discontinuations (15 of 16) were in anthracycline-based regimens. CONCLUSION: Capturing multiple toxicity outcomes throughout chemotherapy enables oncologists and patients to understand the range of side effects as they discuss treatment efficacies. Continuous symptom monitoring may aid in the timely development of interventions that minimize toxicity and improve outcomes. IMPLICATIONS FOR PRACTICE: This study investigated patient-reported toxicities for 17 symptoms recorded prospectively during adjuvant and neoadjuvant chemotherapy regimens for early breast cancer. An analysis of four commonly used chemotherapy regimens identified significant differences among regimens in both individual symptoms and total number of symptoms rated moderate, severe, or very severe. Longer chemotherapy regimens, such as anthracycline-based regimens followed by paclitaxel, had higher proportions of symptoms rated major toxicities. The inclusion of patient perspectives on multiple toxicity outcomes at the same time at multiple time points during chemotherapy has the potential for improving patient-provider communication regarding symptom management, patient satisfaction, and long-term clinical outcomes.

Management of Triple-Negative Breast Cancer in Older Patients: How Is It Different?

Triple-negative breast cancer, which affects about 10% of older women with breast cancer, represents a major treatment challenge in this population. Treatment decisions for these patients can best be made based on geriatric assessment, estimated life expectancy, whether the treatment goal is prolonged survival or palliation, the potential benefits and toxicities of a specific treatment, and the patient's personal goals for treatment. Treatment outcomes for healthy older and younger women are similar, but great challenges exist in managing the vulnerable and frail patient. The cornerstone of therapy for early-stage triple-negative breast cancer is local therapy (surgery and radiation) and, for most patients, adjuvant chemotherapy. In the management of metastatic triple-negative breast cancer, all therapy is palliative and chemotherapy is the treatment of choice. Since all treatment modalities in older patients-especially chemotherapy-can affect physical and mental function, a geriatric assessment is key in selecting the most appropriate treatment strategy. Many older patients (older than 70 years) are poor candidates for state-of-the-art therapy, and some who have substantial comorbidities not related to breast cancer may opt for palliative and hospice care. In this review, we will discuss the role of geriatric assessment, alternative treatment modalities for older women with triple-negative breast cancer, and other special considerations for this patient population.

Adjuvant treatment for older women with invasive breast cancer.

Older women experience a large share of breast cancer incidence and death. With the projected rise in the number of older cancer patients, adjuvant chemo-, radiation and endocrine therapy management will become a key component of breast cancer treatment in older women. Many factors influence adjuvant treatment decisions including patient preferences, life expectancy and tumor biology. Geriatric assessment predicts important outcomes, identifies key deficits, and can aid in the decision making process. This review utilizes clinical vignettes to illustrate core principles in adjuvant management of breast cancer in older women and suggests an approach incorporating life expectancy and geriatric assessment.

Falls in Older Adults With Cancer: Evaluation by Oncology Providers.

PURPOSE: Falls in older adults are common. Screening for falls is quick, simple, and important because falls increase the risk of morbidity and mortality in older patients with cancer. The aim of this study was to evaluate oncology providers' recognition of and response to falls in older patients with cancer. MATERIALS AND METHODS: From a sample of older patients with cancer who completed a geriatric assessment blinded to oncology providers, we identified patients who self-reported falls within the past 6 months. Their history and physical and/or clinic notes completed by an oncology provider were reviewed for the following: documentation of falls, gait assessment, referral to geriatrics or physical and/or occupational therapy, and measurement of 25-hydroxy vitamin D level. RESULTS: In our sample of older patients with cancer who reported at least one recent fall (N = 125), the average age was 72 years (range, 65 to 93 years), 78% were female, and 62% had a breast cancer diagnosis. Chart reviews showed that 13 (10%) had falls documented, 25 (20%) had a gait assessment, eight (6%) were referred, and 21 (17%) had vitamin D level measured. CONCLUSION: We found that only 10% of older patients with cancer who self-reported a recent fall had appropriate medical record documentation. Oncologists are often the primary care providers for older patients and are largely unfamiliar with the frequency and impact of falls in this population. There is a need to increase awareness of falls prevalence and consequences among oncology providers in order to provide timely interventions to reduce the risks associated with falls.

Geriatric assessment-identified deficits in older cancer patients with normal performance status.

BACKGROUND: We investigated whether a brief geriatric assessment (GA) would identify important patient deficits that could affect treatment tolerance and care outcomes within a sample of older cancer patients rated as functionally normal (80%-100%) on the Karnofsky performance status (KPS) scale. METHODS: Cancer patients aged ≥65 years were assessed using a brief GA that included both professionally and patient-scored KPS and measures of comorbidity, polypharmacy, cognition, function, nutrition, and psychosocial status. Data were analyzed using descriptive statistics and multivariable logistic regression. RESULTS: The sample included 984 patients: mean age was 73 years (range: 65-99 years), 74% were female, and 89% were white. GA was conducted before (23%), during (41%), or after (36%) treatment. Overall, 54% had a breast cancer diagnosis (n = 528), and 46% (n = 456) had cancers at other sites. Moreover, 81% of participants (n = 796) had both professionally and self-rated KPS ≥80, defined as functionally normal, and those patients are the focus of analysis. In this subsample, 550 (69%) had at least 1 GA-identified deficit, 222 (28%) had 1 deficit, 140 (18%) had 2 deficits, and 188 (24%) had ≥3 deficits. Specifically, 43% reported taking ≥9 medications daily, 28% had decreased social activity, 25% had ≥4 comorbidities, 23% had ≥1 impairment in instrumental activities of daily living, 18% had a Timed Up and Go time ≥14 seconds, 18% had ≥5% unintentional weight loss, and 12% had a Mental Health Index score ≤76. CONCLUSION: Within this sample of older cancer patients who were rated as functionally normal by KPS, GA identified important deficits that could affect treatment tolerance and outcomes.

Geriatric assessment as an aide to understanding falls in older adults with cancer.

PURPOSE: In older adults, falls are a common cause of functional decline, institutionalization, and reduced quality of life. This study (1) investigates the prevalence of falls in a large sample of community-dwelling older adults with a cancer diagnosis and (2) evaluates the association of falls with domains of comprehensive geriatric assessment (CGA) that pertain to falls risk. METHODS: Patients completed a CGA that includes a self-reported measure of number of falls in the past 6 months. Summary statistics are used to describe prevalence of falls and associations with hypothesized risk factors using Fisher's exact tests and multivariable logistic regression. RESULTS: A total of 1172 patients were enrolled, mean age 73 (65-99), 74 % female, and 89 % Caucasian. Two hundred fifty-six (22 %) reported one or more falls within the last 6 months. Patients with at least one instrumental activities of daily living (IADL) or physical function deficit had more falls as compared those with no deficits identified (p ≤ 0.001). The number of daily medications, comorbidities, Timed Up and Go score >14 s, and poor vision were also associated with increased falls (p ≤ 0.001). Reduced physical function, poor vision, and low performance status had the highest adjusted odds ratio (3.6, 3.4, and 3.0, respectively) for falls. CONCLUSIONS: There is a high prevalence of falls in community-dwelling older patients with a cancer diagnosis. Falls are significantly associated with several measures of geriatric assessment including IADL, physical function, comorbidities, medications, and vision. Timely identification and management of risk factors for falls are important considerations in the care of older cancer patients.

Effect of cytotoxic chemotherapy on markers of molecular age in patients with breast cancer.

BACKGROUND: Senescent cells, which express p16 (INK4a) , accumulate with aging and contribute to age-related pathology. To understand whether cytotoxic agents promote molecular aging, we measured expression of p16 (INK4a) and other senescence markers in breast cancer patients treated with adjuvant chemotherapy. METHODS: Blood and clinical information were prospectively obtained from 33 women with stage I to III breast cancer at four time points: before anthracycline-based chemotherapy, immediately after anthracycline-based chemotherapy, 3 months after anthracycline-based chemotherapy, and 12 months after anthracycline-based chemotherapy. Expression of senescence markers p16 (INK4a) and ARF mRNA was determined using TaqMan quantitative reverse-transcription polymerase chain reaction in CD3(+) T lymphocytes, telomere length was determined by Southern analysis, and senescence-associated cytokines were determined by enzyme-linked immunosorbent assay. Findings were independently assessed in a cross-sectional cohort of 176 breast cancer survivors enrolled a median of 3.4 years after treatment; 39% previously received chemotherapy. All statistical tests were two-sided. RESULTS: In prospectively analyzed patients, expression of p16 (INK4a) and ARF increased immediately after chemotherapy and remained elevated 12 months after treatment. Median increase in log2 p16 (INK4a) was 0.81 (interquartile range = 0.28-1.62; Wilcoxon signed-rank P < .001), or a 75% absolute increase in expression, equivalent to the increase observed over 14.7 years of chronological aging. ARF expression was comparably increased (P < .001). Increased expression of p16 (INK4a) and ARF was associated with dose-dense therapy and hematological toxicity. Expression of two senescence-associated cytokines (VEGFA and MCP1) was durably increased by adjuvant chemotherapy. Telomere length was not affected by chemotherapy. In a cross-sectional cohort, prior chemotherapy exposure was independently associated with a log2-increase in p16 (INK4a) expression of 0.57 (repeated measures model, P < .001), comparable with 10.4 years of chronological aging. CONCLUSIONS: Adjuvant chemotherapy for breast cancer is gerontogenic, inducing cellular senescence in vivo, thereby accelerating molecular aging of hematopoietic tissues.

Feasibility of geriatric assessment in community oncology clinics.

OBJECTIVE: Emerging results support the value of geriatric assessment (GA) in determining the risk and benefits of cancer treatment in older adults. A brief GA tool consisting of valid and reliable measures has been developed; however, little data exist on the ability to perform the GA in community oncology clinics. The objective of this study was to determine the feasibility of performing the GA in the community. MATERIALS AND METHODS: Patients aged ≥65 were eligible. The GA included a health care provider assessment of performance status, cognitive function, a Timed Up and Go test, and a self-administered patient questionnaire that evaluated measures of functional status, comorbidity, psychological state, social support, and nutritional status. RESULTS: From 2009 to 2013, 1088 patients were assessed including 339 (31%) from seven community clinics across North Carolina. The median amount of time to complete the patient-report portion of the GA was 19min in the academic center versus 22min in the community. The median amount of time to complete the entire GA was 23min in the academic center and 30min in community settings. Significantly more patients in the community required assistance completing the questionnaire (24% vs. 14%); however, most patients required no assistance (76%). CONCLUSION: A brief GA can be performed in community oncology clinics. The time to complete the professional assessments and patient self-assessments were similar in both settings. Future studies are planned to determine if such assessments can improve cancer care for older patients.