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Background Delivery of cancer treatments, such as chemotherapy, requires a complex set of decisions that can change over time. Traditional measures of chemotherapy delivery, such as relative dose intensity, measure the amount of chemotherapy received by the end of treatment but mask the timing of dose reductions, delays, and discontinuation. These events may be important for delivering timely interventions to support adherence and lower the risk of recurrence. Materials and Methods We used an institutional database to identify women diagnosed with stage I-III breast cancer receiving adjuvant chemotherapy with a standard 4-cycle regimen of docetaxel + cyclophosphamide (TC, every 21 days) from April 2014 to December 2019. LCD was calculated as the amount of a given chemotherapy agent delivered at a specified time, t , divided by the total planned standard chemotherapy dose at time t. We visualized LCD curves for each chemotherapy agent and reported the median LCD and interquartile range (IQR) at the end of the regimen, overall and by age group (<65 years vs. 65+ years). Results The study population included 80 women. At the end of treatment, overall median LCDs for both cyclophosphamide and docetaxel were 100% (IQR: 99.6%, 100%), suggesting that TC was well tolerated. However, the lower quartile LCD for cyclophosphamide was 98.7% in older women treated with TC compared with 99.7% in younger women. Conclusion Within our cohort, adjuvant TC was well tolerated with LCD curves showing largely on-time and full-dose administration. Subgroup analyses showed only slight decreases in adjuvant TC LCD for patients aged 65+ versus <65 years. [ABSTRACT FROM AUTHOR]

Purpose: Examine baseline fatigue levels in early-breast cancer survivors (EBCS) compared to inactive controls (CON) and identify associated physical and psychosocial factors with fatigue prior to community-based exercise.Methods: A total of 33 EBCS (53.9 ± 11.4 years) and 21 CON (54.0 ± 8.0 years) were recruited. Participants completed questionnaires for demographics and patient-reported outcome measures pertaining to fatigue, quality of life, mental health, and physical activity, and completed a 6-min walk test, balance assessment, cardiopulmonary exercise test (VO2peak), and muscular strength test. A Mann-Whitney U test compared fatigue between groups and unadjusted univariable linear regressions were used to explore relationships with fatigue.Results: Fatigue in EBCS was not statistically different from CON (EBCS: 16.9 ± 5.75; CON: 14.2 ± 3.4, p = 0.121). Univariable analyses showed lower fatigue in EBCS was associated with better Physical and Mental Health (both R2 = 0.435; p < 0.01), better outcome expectations for exercise (R2 = 0.237; p < 0.01), better self-efficacy (R2 = 0.407; p < 0.01), lower depression (R2 = 0.383; p < 0.001), lower anxiety (R2 = 0.104; p < 0.05), and better balance (R2 = 0.265; p < 0.01). Lower fatigue in the CON group was associated with better sleep quality (R2 = 0.263; p < 0.05) and self-efficacy (R2 = 0.417; p < 0.05).Conclusions: Mild fatigue was prevalent in EBCS, whereas moderate/severe fatigue was not. This discrepancy should be explored provided the benefits of exercise for fatigue management. Further, fatigue in EBCS was associated with multiple psychosocial and functional outcomes, which emphasized both its multi-factorial nature and uniqueness to the EBCS population.Trial Registration: Clinicaltrials: gov Number: NCT03760536. [ABSTRACT FROM AUTHOR]

Background: Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single‐item reports. Materials and Methods: Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log‐binomial regression. Cohen's kappa was used to assess agreement between patient‐ and clinician‐reported symptoms. Results: In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient‐provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk [RR], 2.17; 95% confidence interval [CI], 1.36–3.45) and anxiety (RR, 1.48; 95% CI, 1.05–2.09). Conclusion: Oncologists frequently underestimate patients' depression and anxiety and should consider incorporating patient‐reported outcomes to enhance monitoring of mental health symptoms. Implications for Practice: In this sample of 256 patients with breast cancer, depression and anxiety, measured using single‐item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient‐reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients' mental health symptoms. The use of patient‐reported, single‐item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients' psychological health. Depression and anxiety are underrecognized and undermanaged in oncology practice. This article describes the severity of depression and anxiety and associated factors in women with early breast cancer undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Despite current definitions of geriatric, there is no age at which a patient is technically considered older. Geriatric assessment deficits may have implications for younger patients too. This article explores the frequency of geriatric assessment deficits identified in younger patients and examines the value of this tool in a sample that includes both younger (<65 years) and older (≥65 years) women with early breast cancer. [ABSTRACT FROM AUTHOR]

Background: Despite data demonstrating the safety of omitting axillary surgery in older women with early-stage breast cancer, the incidence of axillary surgery remains high. It was hypothesized that the prevalence of nodal positivity would decrease with advancing age.Methods: The National Cancer Data Base was used to construct a cohort of adult women with early-stage, clinically node-negative, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative breast cancer treated between 2013 and 2015. Multivariable logistic regression was used to assess the relationship between age and nodal positivity, and this was stratified by the axillary surgery category. Modified Poisson regression was used to estimate the proportion of women receiving adjuvant therapy according to age and nodal status.Results: The incidence of axillary surgery among women aged 70 and older (n = 51,917) remained high nationwide (86%). There was a significant decrease in nodal positivity with advancing age in women with early-stage, ER+, clinically node-negative breast cancer from the youngest cohort up to patients aged 70 to 89 years, and this was independent of histologic subtype (ductal vs lobular), race, comorbidities, and socioeconomic factors. Overall, less than 10% of women aged 70 or older who underwent surgery had node-positive disease, regardless of axillary surgery type, and almost 95% of node-positive patients aged 70 or older were at pathological stage N1mi or N1.Conclusions: Axillary surgery may be safely omitted for many older women with ER+, clinically node-negative, early-stage breast cancer. Nodal positivity declines with advancing age, and this suggests varied biology in older patients versus younger patients. [ABSTRACT FROM AUTHOR]

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Purpose: A few previous studies report a direct relationship between older age and chemotherapy‐induced neuropathy. This study further evaluated this adverse event's age‐based risk. Methods: CALGB 40101 investigated adjuvant paclitaxel (80 mg/m2 once per week or 175 mg/m2 every 2 weeks) in patients with breast cancer and served as a platform for the current study that investigated age‐based differences in neuropathy. Grade 2 or worse neuropathy, as per Common Terminology Criteria for Adverse Events version 4, was the primary endpoint; patients were assessed at baseline, every 6 months for 2 years, and then annually for 15 years. Results: Among these 1,881 patients, 230 were 65 years of age or older, 556 were 55–64 years, and 1,095 were younger than 55; 1,226 neuropathy events (commonly grade 1 or 2) were reported in 65% of the cohort. The number of grade 2 or worse events was 63 (27%), 155 (28%), and 266 (24%) within respective age groups (p =.14). In univariate analysis, only motor neuropathy had a higher age‐based incidence: 19 (8%), 43 (8%), and 60 (5%), respectively (p =.04); in multivariate analyses, this association was no longer statistically significant. Other endpoints, such as time to onset of neuropathy (time from trial enrollment to neuropathy development) and time to improvement (time from maximal grade sensory neuropathy to a one‐category improvement), showed no statistically significant age‐based differences. In contrast, obesity was associated with neuropathy, and every 2‐week paclitaxel was associated with trends toward neuropathy. Conclusion: Although paclitaxel‐induced neuropathy is common, older age is not an independent risk factor. Clinical trial identification number. NCT00041119 (CALGB 40101). Implications for Practice: Age alone is not an independent risk factor for paclitaxel‐induced neuropathy. Mixed results have been reported regarding whether older cancer patients are at a greater risk for chemotherapy‐induced neuropathy. This article further evaluates the age‐based risk of this adverse event. [ABSTRACT FROM AUTHOR]

Abstract: Skeletal muscle loss, commonly known as sarcopenia, is highly prevalent and prognostic of adverse outcomes in oncology. However, there is limited information on adults with early breast cancer and examination of other skeletal muscle indices, despite the potential prognostic importance. This study characterizes and examines age‐related changes in body composition of adults with early breast cancer and describes the creation of a novel integrated muscle measure. Female patients diagnosed with stage I‐III breast cancer with abdominal computerized tomography (CT) scans within 12 weeks from diagnosis were identified from local tumor registry (N = 241). Skeletal muscle index (muscle area per height [cm2/m2]), skeletal muscle density, and subcutaneous and visceral adipose tissue areas, were determined from CT L3 lumbar segments. We calculated a novel integrated skeletal measure, skeletal muscle gauge, which combines skeletal muscle index and density (SMI × SMD). 241 patients were identified with available CT imaging. Median age 52 years and range of 23‐87. Skeletal muscle index and density significantly decreased with age. Using literature based cut‐points, older adults (≥65 years) had significantly higher proportions of sarcopenia (63 vs 28%) and myosteatosis (90 vs 11%) compared to younger adults (<50 years). Body mass index was positively correlated with skeletal muscle index and negatively correlated with muscle density. Skeletal muscle gauge correlated better with increasing age (ρ = 0.52) than with either skeletal muscle index (ρ = 0.20) or density (ρ = 0.46). Wide variations and age‐related changes in body composition metrics were found using routinely obtained abdominal CT imaging. Skeletal muscle index and density provide independent, complementary information, and the product of the two metrics, skeletal muscle gauge, requires further research to explore its impact on outcomes in women with curable breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: Background: Our ability to optimize the care of older adults with cancer and comorbid illnesses is insufficient because most clinical trials lack systematic measurement. The primary purpose of this study was to evaluate the association between patient‐reported comorbidity and all‐cause mortality using various comorbidity scoring algorithms. Materials and Methods: The Carolina Senior Registry was linked with the North Carolina Central Cancer Registry to obtain mortality data. Comorbidity was assessed using the patient‐reported Older Americans Resources and Services Questionnaire subscale that assesses 13 specific conditions and the degree to which each impairs activities. Multivariable Cox proportional hazard regression models were used to evaluate the association between comorbidities and all‐cause mortality. Results: The study sample included 539 patients; the median age was 72 years, 72% were female, and 47% had breast cancer. Overall, 92% reported ≥1 comorbid condition, with a mean of 2.7 conditions (range 0–10), with arthritis and hypertension the most common (52% and 50%, respectively). Approximately 60% reported a functional limitation related to comorbidity. After adjusting for time from diagnosis to geriatric assessment, age, cancer type, and stage, the risk of death increased by 5% for each unit increase in comorbidity burden score (adjusted hazard ratio [HR] = 1.05, 95% confidence interval [CI]: 1.01–1.10) and 12% for each comorbid condition impacting function (HR = 1.12, 95% CI: 1.02–1.23). Conclusion: Comorbid conditions in older adults with cancer are highly prevalent and associated with all‐cause mortality, particularly those conditions that impair function. Routine comorbidity assessment should be included in clinical trials and can be measured via a simple one‐page patient‐reported questionnaire. Implications for Practice: In order to optimize and personalize the care of older adults with cancer, systematic measurement of comorbidities is necessary in both clinical trials and routine practice. Patient‐reported comorbid conditions in older adults with cancer are highly prevalent and are associated with increased risk of all‐cause mortality, particularly for those conditions that impair function. Comorbidity can be systematically measured via a one‐page patient‐reported questionnaire and should be incorporated into future clinical trials and considered for use in oncology clinics to aid in assessing older adults with cancer. [ABSTRACT FROM AUTHOR]

Background. Although breast cancer during pregnancy (BCDP) is rare (occurring with only 0.4% of all BC diagnoses in female patients aged 16-49 years), management decisions are challenging to both the patient and the multidisciplinary team. Materials and Methods. Experts in breast cancer at the University of North Carolina conducted a targeted literature search regarding the multidisciplinary treatment approaches to BCDP: medical, surgical, and radiation oncology. Supportive care, including antiemetic agents, and imaging approaches were also reviewed. Results. Review of the literature revealed key points in the management of BCDP. Surgical management is similar to that in nonpregnant patients; pregnant patients may safely undergo breast-conserving surgery. Recommendations should be tailored to the individual according to the clinical stage, tumor biology, genetic status, gestational age, and personal preferences. Anthracycline-based chemotherapy can be safely initiated only in the second and third trimesters. The rate of congenital abnormalities in children exposed to chemotherapy is similar to the national average (approximately 3%). Dosing of chemotherapy should be similar to that in the nonpregnant patient (i.e., actual body surface area). Antihuman epidermal growth factor receptor 2 therapy, radiation, and endocrine treatment are contraindicated in pregnancy and lactation. Care should include partnership with obstetricians. The literature regarding prognosis of BCDP is mixed. Conclusion. To maximize benefit and minimize risk to the mother and fetus, an informed discussion with the patient and her medical team should result in an individualized treatment plan, taking into account the timing of the pregnancy and the stage and subtype of the breast cancer. Because BCDP is rare, it is essential to collect patient data in international registries. [ABSTRACT FROM AUTHOR]

Background: Discordance in hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status between primary tumors and metastatic sites for breast cancer is well established. However, it is uncertain which patient-related factors lead to biopsy when metastases are suspected and whether having a biopsy impacts survival.Methods: The medical charts of metastatic breast cancer (MBC) patients diagnosed January 2000-August 2014 were retrospectively reviewed. A biopsy was defined as a procedure where tissue was obtained and assessed for both HR and HER2. Both bivariate and multivariate analyses were performed to assess patient characteristics related to biopsy and whether having a biopsy was associated with improved survival.Results: Of 409 patients suspected of having MBC, 165 (40%) had a biopsy, and 34% of these had discordant HR or HER2 status when compared to the initial diagnosis. In multivariate analysis, having a biopsy was associated with: recurrence in years 2010-2014, disease-free interval of > =3 years, stage 0-IIA at presentation, suspected locoregional recurrence, being HR+/HER2-, or missing HR/HER2 at diagnosis. A similar multivariate analysis revealed that having a biopsy was associated with improved survival (HR = 0.67, p = 0.002). The association of biopsy and improved survival was noted in specific subgroups: patients with missing HR and HER2 data at initial diagnosis (p = 0.001), those without metastases in liver, lung or brain (p = 0.001), and being younger than 70 years old at recurrence (p < 0.001).Conclusions: Specific clinical factors were associated with biopsy at the time of suspected recurrence. Having a biopsy was associated with reduced mortality. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer survivors on aromatase inhibitors (AI) often experience side effects of joint pain, stiffness, or achiness (arthralgia). This study presents findings from a qualitative study of survivors on an AI regarding their knowledge of potential joint pain side effects and how both AI side effects and their management through moderate physical activity could be discussed during routine visits with their oncology provider.Methods: Qualitative data from semi-structured interviews were content analyzed for emergent themes. Descriptive statistics summarize sample characteristics.Results: Our sample included 36 survivors, mean age of 67 (range 46-87); 86 % Caucasian and 70 % had education beyond high school. AI experience are as follows: 64 % anastrozole/Arimidex, 48 % letrozole/Femara, and 31 % exemestane/Aromasin. Participants expressed interest in having more information about potential joint pain side effects when the AI was prescribed so they could understand their joint symptoms when they appeared or intensified. They were relieved to learn that their joint symptoms were not unusual or "in their head." Participants would have been especially motivated to try walking as a way to manage their joint pain if physical activity had been recommended by their oncologist.Conclusions: Breast cancer survivors who are prescribed an AI as part of their adjuvant treatment want ongoing communication with their oncology provider about the potential for joint pain side effects and how these symptoms may be managed through regular physical activity. The prescription of an AI presents a "teachable moment" for oncologists to recommend and encourage their patients to engage in regular physical activity. [ABSTRACT FROM AUTHOR]

Background: National guidelines recommend that patients with a cancer diagnosis engage in regular physical activity to reduce cancer-related fatigue, maintain quality of life and physical function, and improve overall prognosis and survival. This study investigates oncology provider communications about physical activity during routine clinic visits with patients with early-stage breast, colon, or prostate cancer.Methods: This study used a retrospective chart review for documentation of inquiries or recommendations pertaining to physical activity in clinician notes and after-visit patient summaries.Results: In a 1-month period, 55 oncology providers had 361 encounters (clinic visits) with early-stage cancer patients. Thirty-five percent of these encounters included a provider communication about "physical activity," "exercise," or "activity." Encounters with a medical oncologist resulted in a physical activity communication 55% of the time, whereas encounters with other clinician specialties did so 20% of the time (P < .0001). The likelihood of a physical activity communication increased with patient age (P < .001). When the encounter was with a patient who was being seen for surveillance, chemotherapy, or endocrine treatment, the rate of physical activity communications was significantly higher (46%, 37%, and 58%, respectively) than the rate when the visit was during radiation treatment or surgery (6% and 19%, respectively; P < .0001).Conclusions: This study shows that it is feasible for oncology providers to have physical activity communications during routine clinic visits; however, the frequency of physical activity communications varies among providers. Interventions are needed to remind and encourage all oncology providers to encourage their patients with early-stage cancer to be physically active. . [ABSTRACT FROM AUTHOR]

Purpose. Breast cancer (BC) is a disease of aging and the number of older BC patients in the U.S. is rising. Immunohistochemical data show that with increasing age, the incidence of hormone receptor-positive tumors increases, whereas the incidence of triple-negative tumors decreases. Few data exist on the frequency of molecular subtypes in older women. Here, we characterize the incidence and outcomes of BC patients by molecular subtypes and age. Patients and Methods. Data from 3,947 patients were pooled frompublicly available clinical and gene expression microarray data sets. The PAM50 algorithm was used to classify tumors into five BC intrinsic subtypes: luminal A, luminal B, HER2- enriched, basal-like, and normal-like.The association of age and subtypewithrecurrence-freesurvival (RFS),overallsurvival,and disease-specific survival (DSS) was assessed. Results. The incidence of luminal (A, B, and A1B) tumors increased with age (p , .01, p , .0001, and p , .0001, respectively), whereas the percentage of basal-like tumors decreased (p , .0001). Among patients 70 years and older, luminal B, HER2-enriched, and basal-like tumors were found at afrequencyof32%,11%,and9%,respectively. In olderwomen, luminal subtypes had better outcomes than basal-like and HER2-enriched subtypes. After controlling for subtype, treatment, tumor size,nodal status, and grade, increasingage had no impact on RFS or DSS. Conclusion. MorefavorableBCsubtypes increasewith age, but older patients still have a substantial percentage of high-risk tumor subtypes. After accounting for tumor subtypes, age at diagnosis is notan independent prognostic factor for outcome. [ABSTRACT FROM AUTHOR]

Approximately 40,000 women die as a result of breast cancer each year and many more live with advanced disease. When breast cancer recurs, the goals of treatment often shift from one of cure to controlling the disease for as long as possible while palliating symptoms interfering with the patient's functional status and quality of life. This requires ongoing discussions with the patient and family about the goals of care. Many symptoms depend on the site of metastasis, with bone being the most frequent, and commonly occur with fatigue, depression, insomnia, and pain. The purpose of this paper is to identify and provide an overview of the management of the most common symptoms in patients with breast cancer metastases. [ABSTRACT FROM AUTHOR]

In the U.S., cancer is a disease of aging. The average 65- year-old patient has an anticipated life expectancy of 20 years, and clinicians should take this into account when making breast cancer management decisions. However, older breast cancer patients can present with wide variations in health status, and treatment in older patients should therefore include a careful evaluation of comorbidities, physical function, polypharmacy, and other issues that could potentially impact a patient's ability to undergo chemotherapy without excessive risk. Evaluation tools are under development, including potential molecular markers, to identify which older patients are the best candidates for chemotherapy, as well as those more susceptible to actually developing cancer. Standard chemotherapy regimens are just as effective in older patients as they are in the younger population, and can substantially prolong life expectancy when used in the right patients. This article discusses breast cancer in seniors, including the epidemiology of breast cancer in these patients, the potential impact of comorbidities, and effective adjuvant therapy in selected older patients. [ABSTRACT FROM AUTHOR]

In the U.S., cancer is a disease of aging. The average 65-year-old patient has an anticipated life expectancy of 20 years, and clinicians should take this into account when making breast cancer management decisions. However, older breast cancer patients can present with wide variations in health status, and treatment in older patients should therefore include a careful evaluation of comorbidities, physical function, polypharmacy, and other issues that could potentially impact a patient's ability to undergo chemotherapy without excessive risk. Evaluation tools are under development, including potential molecular markers, to identify which older patients are the best candidates for chemotherapy, as well as those more susceptible to actually developing cancer. Standard chemotherapy regimens are just as effective in older patients as they are in the younger population, and can substantially prolong life expectancy when used in the right patients. This article discusses breast cancer in seniors, including the epidemiology of breast cancer in these patients, the potential impact of comorbidities, and effective adjuvant therapy in selected older patients. [ABSTRACT FROM AUTHOR]

The article presents a medical report concerning estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. The article suggests the much progress has been made in the treatment of early stage breast cancer, and that in patients with hormone-sensitive tumors, tamoxifen reduces the risk of recurrence and death by more than 30%. Additionally, treatment with aromatase inhibitors further reduces the risk of recurrence in post-menopausal women with estrogen-receptor positive tumors.

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.

Breast cancer is the most common cancer in women, with an incidence that rises dramatically with age. The average age at diagnosis of breast cancer is 61 years, and the majority of woman who die of breast cancer are age 65 years and older. Major improvements in public health and medical care have resulted in dramatic increases in longevity. The oldest old (those age 80 years and older) are a rapidly expanding group and now comprise 9 million members of the US population. The treatment of individuals who are age 80 years and older is complex and involves clearly defining the goals and value of treatment while also weighing risks, such as the potential effects of treatment on functional loss and quality of life. Limited evidence-based treatment guidelines exist for the caring of this older cohort of patients with breast cancer. Data from clinical trials that enroll primarily younger patients lack the information needed to estimate the likelihood of toxicities that can be life changing in older adults. Clinicians who make treatment recommendations should place the available evidence in the context of the patient's life expectancy and geriatric assessment results that include an evaluation of a patient's functional status, comorbidities, cognition, social support, nutritional status, and psychological state. Furthermore, these decisions should be placed in the context of the patient's goals for treatment, preferences, and values. This review summarizes the current literature and focuses on the role of geriatric assessment in treatment recommendations for patients age 80 years and older with early and metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated associations among comorbidity, toxicity, time to relapse (TTR), and overall survival (OS) in older women with early-stage breast cancer receiving adjuvant chemotherapy. Methods: Cancer and Leukemia Group B 49907 (Alliance) randomly assigned women 65 years old with stages I-III breast cancer to standard adjuvant chemotherapy or capecitabine. We reviewed data from 329 women who participated in the quality of life companion study CALGB 70103 and completed the Physical Health Subscale of the Older American Resources and Services Questionnaire. This questionnaire captures data on 14 comorbid conditions and the degree to which each interferes with daily activities. A comorbidity burden score was computed by multiplying the total number of conditions by each condition's level of interference with function. Outcomes were grade 3 to 5 toxicity, TTR, and OS. Logistic regression was used to evaluate associations between comorbidity and toxicity, and Cox proportional hazards models for TTR and survival. Results: Number of comorbidities ranged from 0 to 10 (median 2); the comorbidity burden score ranged from 0 to 25 (median 3). The most common conditions were arthritis (58%) and hypertension (55%). Comorbidity was associated with shorter OS, but not with toxicity or TTR. The hazard of death increased by 18% for each comorbidity (hazard ratio [HR]=1.18, 95% CI=1.06 to 1.33) after adjusting for age, tumor size, treatment, node and receptor status. Comorbidity burden score was similarly associated with OS (HR=1.08; 95% CI, 1.03 to 1.14). Conclusions: Among older women enrolled onto a clinical trial, comorbidity was associated with shorter OS, but not toxicity or relapse. [ABSTRACT FROM AUTHOR]

Cancer treatment is associated with skeletal muscle loss, leading to reductions in muscular strength and functional capacity. Exercise training can improve muscular strength in breast cancer survivors (BCS), even without skeletal muscle hypertrophy. Factors such as improved muscle quality (MQ) may contribute to improved function but limited data are available in BCS. PURPOSE: To investigate the effects of exercise training in BCS and healthy controls (HC) on MQ, cross-sectional area (CSA), muscular strength, and physical function and to examine associations between these measures. METHODS: BCS (n=31, 54 [11] y, 27.5 [5.0] kg/m²) and HC (n=15, 54 [8] y, 29.3 [4.9] kg/m²) underwent a 16-week combined aerobic and strength training intervention 3x/week for one-hour at a community-based exercise program for BCS. Isokinetic peak torque and maximal voluntary isometric contraction (MVIC) were assessed in the knee extensor muscles. Ultrasound was used to determine muscle CSA and echo intensity of the vastus lateralis. Functional parameters included 6-minute walk (6MWT) and timed up and go (TUG). All measures were taken pre- and post-intervention and were analyzed using a 2x2 repeated measures ANOVA and Pearson's correlations. Data are mean change [SD]. RESULTS: Echo intensity decreased with training overall (-5.4 [24.6], p=.046), indicating higher MQ, with no change in CSA. A time x group interaction for MVIC showed increased strength after training in BCS (+11.0 [17.2] N·m, p=.001) but not HC (-2.6 [23.7] N·m, p=.673). Physical function improved in both groups (TUG -0.5 [0.9] sec, p<.000; 6MWT 35.5 [45.0] m, p<.001). At baseline, echo intensity was inversely correlated with MVIC, TUG and 6MWT in HC only (r= -0.451-0.490, all p<0.05). No associations in the changes of these variables were observed with training. CONCLUSION: A 16-week exercise intervention improved MQ and functional measures in both BCS and HC, while MVIC increased only in BCS. MQ was moderately correlated with functional and strength measures at baseline in HC but not in BCS. The lack of correlations in BCS suggest that other factors, possibly neural adaptations, may be responsible for the improvements in muscular strength and functional measures seen after an exercise intervention rather than improvements in MQ and CSA. [ABSTRACT FROM AUTHOR]

Breast cancer treatment has been shown to alter carbohydrate, lipid, and lactate metabolism at rest and during acute, steady-state exercise. Currently, it is unknown if chronic exercise training can mitigate the metabolic dysfunction observed in breast cancer survivors (BCS). PURPOSE: To assess differences in substrate utilization between BCS and sedentary-healthy controls (HC) before and after a community-based exercise training program. METHODS: Early stage (0-III), non-metastatic BCS (n=28, age 55±11, BMI 27.4±4.9kg/m²) and age-matched HC (n=15, age 54±8, BMI 29.3±4.9kg/m²) completed a cardiopulmonary exercise test (CPET) before and after a 16-week combined aerobic and resistance training intervention. Respiratory exchange ratio (RER) values were derived based on percentages of absolute peak power output (PPO) achieved during the CPET, along with 3-minute post-exercise blood lactate (3MBL) measures, to estimate substrate utilization. RESULTS: Prior to training, overall RER values increased from 40% to 60% to 70% of PPO (0.84±0.06; 0.93±0.07; 0.98±0.07), with all values being different from each other (all p<0.001), with no group differences. There was a trend towards group differences in 3MBL (BCS: 6.4±1.9 mmol/L, HC: 7.2± 2.0 mmol/L, p=0.072). Following training, CPET PPO increased in BCS (Δ16.3±2.5 W, p<0.001) and HC (Δ6.7±2.5 W, p=0.020). However, RER values were unchanged with training at each intensity. Overall, 3MBL trended towards being higher (PRE: 6.9±1.9 mmol/L, POST: 7.5±2.1 mmol/L, p=0.075). CONCLUSIONS: There were no observed differences in substrate utilization during acute exercise between groups, in contrast to previous work. Additionally, RER at various intensities was not impacted by the training intervention, which may be due to a lack of a steady state during the CPET. Greater PPO after training may have allowed BCS and HC to work at a higher wattage relative to RER, which could have diminished differences in RER. While BL was lower in BCS before training, the response in both groups appeared to increase following the intervention and may reflect improved carbohydrate metabolism. [ABSTRACT FROM AUTHOR]

The ability to maintain balance and postural control are crucial for performing daily activities and preventing falls. Balance worsens with age and decreases can be exacerbated by other conditions, such as breast cancer treatment with chemotherapy. Exercise interventions are one potential method of maintaining or improving balance but have not been extensively investigated in breast cancer survivors (BCS). PURPOSE: To analyze the effect of a 16-week exercise training intervention on balance in BCS and healthy age-matched sedentary controls (HC). Exploratory aims investigated a relationship between muscle strength and balance changes, as well as differences in BCS displaying chemotherapy induced peripheral neuropathy (CIPN) versus those who did not. METHODS: BCS (n=30 women, 54.6 yrs (12.0), BMI 27.8 kg/m² (5.2), n=11 with CIPN) and HC (n=14 women, 54.6 yrs (8.4), BMI 28.9kg/m² (4.9)) had balance assessed using a Neurocom Smart Balance Master Sensory Organization Test (SOT) before and after a 16-week combined aerobic and resistance training intervention, at a community-based program. Visual, somatosensory, vestibular, preference, and composite scores were evaluated from the SOT. Maximal isometric voluntary contraction (MIVC), isokinetic peak torque (PT), and rate of torque development (RTD) of the knee extensors were determined as measures of strength and power, respectively. RESULTS: At baseline, no statistical group differences in SOT scores were observed. Overall, vestibular [Pre: 69(18), Post: 77(14); p=0.016] and composite [73(11), 79(9); p<0.001] scores improved with training. No difference was found between the BCS and control, or CIPN and non-CIPN participants for any of the SOT measures. PT, RTD, and MIVC were not correlated with composite balance scores. CONCLUSIONS: A 16-week exercise intervention program appears to improve vestibular and composite balance scores for BCS and HC. General exercise interventions may be beneficial for both BCS and healthy women in improving balance to prevent falls with age and in clinical populations, although larger sample size are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

PURPOSE: A preliminary analysis was conducted to assess changes in cancer-related fatigue (CRF) after community-based exercise participation, and to identify associations between CRF and commonly assessed physical and psychological outcomes in early breast cancer survivors (EBCS). METHODS: 29 EBCS (I-III) and 13 sedentary age-matched controls (CON) were included in the analysis (age EBCS: 53.9+11.9 years; CON: 53.8+8.4 years). Pre- and post-intervention measurements for each group included the PROMIS Fatigue 7a, VO2peak, lower and upper body strength, quality of life, depression/anxiety, pain, sleep quality, self-efficacy for fatigue management, physical function, and self-reported physical activity/outcome exercise expectations. Both groups completed 1-hour bouts of combined exercise training 3 days/week for 1 hour each day for 16-weeks. A mixed model ANOVA was used to assess the change in CRF between and within each group in addition to generating Cohen's D effect sizes. Univariate linear regressions were conducted and adjusted R² were obtained to identify associations with CRF. RESULTS: Post-exercise, CRF significantly decreased in EBCS (-2.6, p = 0.001, Cohen's D = 0.51) but not in CON (0.0, p = 0.942, Cohen's D = 0.02). Lower CRF in EBCS was also associated with better overall self-reported quality of life (adj R² = 0.364; p<0.001), less depression (adj R² = 0.223; p<0.01), higher self-efficacy for fatigue self-management (adj R² = 0.433; p<0.01), higher outcome expectations for exercise (adj R² = 0.227; p<0.01), better balance (adj R² = 0.136; p<0.05), 6MWT performance (adj R² = 0.163; p<0.05) and VO2peak (adj R² = 0.121; p<0.05). CONCLUSIONS: Community-based exercise is beneficial for alleviating CRF in EBCS. These improvements were primarily associated with psychosocial outcomes, as well as objectively measured physical outcomes. Though encouraging, more research is needed to determine the true efficacy of community-based exercise for CRF management and possible mediators for its observed improvement in EBCS. Supported by funding from the Breast Cancer Research Foundation of New York. [ABSTRACT FROM AUTHOR]

Decreased immune function from breast cancer treatment may be offset using exercise, although limited data on specific cell types exists and acute and chronic exercise have traditionally been investigated independently. Mucosal associated invariant T (MAIT) cells are primarily anti-microbial but have recently been implicated in tumor defense and demonstrate resistance to chemotherapy-induced declines. PURPOSE: To determine the MAIT cell response to acute exercise before (PRE) and after (POST) exercise training in breast cancer survivors (BCS) and healthy controls (CON). METHODS: Age-matched BCS [n=13, 59 (9) yr] and CON [n=13, 58 (7) yr] performed 45 minutes of intermittent cycling at 60% peak power output before and after a 16 week combined exercise intervention delivered in a community-based setting. Blood samples were obtained at rest, immediately (0h) and 1h after acute exercise. MAIT cell counts, frequency, and intracellular cytokine expression following stimulation were determined using flow cytometry. Data are reported as mean (SD) or 95% CI. RESULTS: At PRE, MAIT cell counts increased m CON at 0h (72 cells/µL, 95% CI 55, 89; p<0.001) and BCS tended to increase (15 cells/µL, 95% CI -2, 33; p=0.086), with mobilization being greater in CON (57 cells/µL, 95% CI 33, 81; p<0.001). CON MAIT cell frequency also increased at 0h (1.7%, 95% CI 1.1, 2.4; p<0.001) with only a trend for BCS (0.7%, 95% CI 1.7, 3.3; p=0.068). There were no changes or group differences in intracellular TNFα+ and IFNγ+ MAIT cell frequency. At POST, there was a group x training interaction trend (p=0.095), with BCS demonstrating a 2-fold increase in MAIT cell mobilization at 0h (33 cells/µL, 95% CI 27, 61; p=0.021) while CON was unchanged from PRE (8 cells/µL, 95% CI -13, 29; p=0.967). Independent of group, TNFα+ MAIT cell frequency tended to be higher at 0h (12%, 95% CI 0.15, 24.4; p=0.053) while IFNγ was unchanged. CONCLUSIONS: BCS MAIT mobilization following acute exercise was attenuated. However, exercise training may partially rescue these initial deficits, including greater sensitivity to mitogenic stimulation resulting in the higher TNFα frequency at POST. Using acute stressors before and after exercise interventions provides a unique approach to identify immuno-dysfunction that may be less apparent at rest. [ABSTRACT FROM AUTHOR]