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By the year 2030 most patients with breast cancer will be aged 65 years or more and many will be frail. Frailty implies diminished physiologic reserve; contributors include diminished organ function, comorbidities, impaired physical function, and geriatric syndromes. Time-efficient tools for assessing frailty are being developed and, once validated, can be used to identify frail cancer patients and help direct therapy. Screening mammography in frail patients is questionable, and a clinical breast exam is likely to identify breast cancers that warrant intervention. Hormonal therapy may be a reasonable primary therapy in older frail women with hormone receptor-positive lesions. For estrogen receptor--and progesterone receptor-negative lesions, excision of the primary tumor may be adequate. Adjuvant hormonal therapy may be appropriate in frail elders with high-risk hormone receptor-positive breast cancer; chemotherapy is rarely indicated regardless of tumor status. The majority of frail elders with metastases will have hormone receptor-positive breast cancers, and endocrine therapy should be considered; those with receptor-negative tumors may be treated with single-agent chemotherapy or supportive care measures. Oncologists need to acquire the skills to appropriately identify frail elders so they select appropriate therapies that will minimize toxicity and maintain quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is common and disabling among cancer survivors. Little is known about the association of CIPN with other measures of the nervous system's integrity, such as executive dysfunction. We compared measures of executive function in older chemotherapy-treated cancer survivors with and without CIPN., Materials and Methods: This cross-sectional study enrolled 50 chemotherapy-treated cancer survivors (65.6 ± 11.5 years, 88% female) post-chemotherapy treatment who were previously referred for outpatient rehabilitation at the request of the cancer survivor or a medical provider. Twenty-two participants (44%) had CIPN defined by patient-reported distal paresthesia or numbness, which began with chemotherapy and continued to the time of cognitive testing. Measures of executive function included Trails-B, Stroop, and rapid reaction accuracy (RRA) and were evaluated between cancer survivors with and without CIPN using t-tests. Multivariable models were then used to determine whether CIPN was an independent determinant of the measures of executive function (Trails-B, Stroop Incongruent, and RRA). Models were adjusted for age, sex, history of anxiety, and benzodiazepine use due to their known associations with CIPN and executive function., Results: Cancer survivors with CIPN (CIPN+) had reduced executive function compared to survivors without CIPN (CIPN-) on Trails-B (CIPN+: 84.9 s ± 44.1 s, CIPN-: 59.1 s ± 22.5 s, p = 0.01), Stroop (CIPN+: 100.6 s ± 38.2 s, CIPN-: 82.1 s ± 17.3 s, p = 0.03), and RRA (CIPN+: 60.3% ± 12.9%, CIPN-: 70.6% ± 15.7%, p = 0.01). There were no differences in cancer stage severity or functional status by patient report or sit-to-stand function. The association between CIPN and reduced executive function was found in multivariable models after adjusting for age, sex, anxiety, and benzodiazepine use for Trails-B (ß:17.9, p = 0.046), Stroop (ß:16.9, p = 0.02), and RRA (ß:-0.072, p = 0.03)., Discussion: In this population, CIPN is associated with reduced executive function in older cancer survivors treated with chemotherapy. Future research is required to further understand this preliminary association, the causality, and the potential risk factors., Competing Interests: Declaration of Competing Interest MKH reports receiving consulting fees from Argenx, Alexion, UCB Pharma, Janssen, and Immunovant; honoraria from Medscape, Springer Health, AANEM, Medlink Neurology, and Continuum Lifelong Learning in Neurology; grants from University of Vermont Medical Center and Myasthenia Gravis Foundation of America; and leadership roles in the Neuromuscular Study Group and AANEM Neuromuscular Fellowship Committee. NK reports funding from the National Cancer Institute; receiving consulting fees from the Eisana Corporation; and receiving honoraria from AANEM. JKR reports funding from the Newman Family Foundation; payment for expert testimony; sharing a patent for the ReacStick with colleagues James Ashton-Miller, James T. Eckner, and Hogene Kim., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The study aimed to determine the feasibility of remotely delivered exercise (tele-exercise) for older, rural cancer survivors and to explore the effects of tele-exercise on physical function, physical activity, and patient-reported outcomes., Methods: Participants were rural cancer survivors age ≥ 60 years (79% female; mean age 70.4 ± 5.7) randomly assigned to the remotely delivered EnhanceFitness (tele-EF) exercise program, inclusive of aerobic, strength, and balance training and led by American Council on Exercise certified instructors for 1 h, 3 days/week for 16 weeks (n = 20) or to a waitlist control group (n = 19). We assessed feasibility, physical function, accelerometer-measured physical activity, and patient-reported outcomes at baseline and post intervention., Results: Among those screened as eligible, 44 (64%) consented to participate with 39 randomized after completing baseline measures. Attrition was equivalent between groups (n = 1, each) with 95% completing the study. The median class attendance rate was 86.9% (interquartile range: 79-94%). Compared to controls, tele-EF participants had statistically significant improvement in the five-time sit-to-stand test (- 3.4 vs. - 1.1 s, p = 0.03, effect size = 0.44), mean daily light physical activity (+ 38.5 vs 0.5 min, p = 0.03, effect size = 0.72) and step counts (+ 1977 vs. 33, p = 0.01, effect size = 0.96). There were no changes in self-efficacy for exercise, fatigue, or sleep disturbance between groups., Conclusions: Findings indicate that tele-EF is feasible in older, rural cancer survivors and results in positive changes in physical function and physical activity., Implications for Cancer Survivors: Tele-EF addresses common barriers to exercise for older, rural cancer survivors, including limited accessible opportunities for professional instruction and supervision., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Declaration of Competing Interest BLM, KM, JM, NK, JAS, HC, MKH, RR, SGB, MR, CR, JKR, NK report no conflicts of interest with the current manuscript. NK reports receiving consulting fees from Eisana Corporation as a medical consultant and honoraria for lectures from AANEM. MKH reports receiving consulting fees from Argenx, Alexion, UCB Pharma, Janssen, and Immunovant and honoraria from Medscape, Springer Health, AANEM, Medlink Neurology, and Continuum Lifelong Learning in Neurology.

Background: Previous studies identified physical function limitations in older cancer survivors, but few have included objective measures and most focused on breast and prostate cancer survivors. The current study compared patient-reported and objective physical function measures between older adults with and without a cancer history., Methods: Our cross-sectional study used a nationally representative sample of community-dwelling, Medicare beneficiaries from the 2015 National Health and Aging Trends Study (n = 7495). Data collected included patient-reported physical function, including a composite physical capacity score and limitations in strength, mobility, and balance, and objectively measured physical performance metrics, including gait speed, five time sit-to-stand, tandem stand, and grip strength. All analyses were weighted to account for the complex sampling design., Results: Thirteen percent of participants (n = 829) reported a history of cancer, of which more than half (51%) reported a diagnosis other than breast or prostate cancer. In models adjusted for demographics and health history, older cancer survivors had lower Short Physical Performance Battery scores (unstandardized beta [B] = -0.36; 95% CI: -0.64, -0.08), slower gait speed (B = -0.03; 95% CI: -0.05, -0.01), reduced grip strength (B = -0.86; 95% CI: -1.44, -0.27), worse patient-reported composite physical capacity (B = -0.43; 95% CI: -0.67, -0.18) and patient-reported upper extremity strength (B = 1.27; 95% CI: 1.07, 1.50) compared to older adults without cancer. Additionally, the burden of physical function limitations was greater in women than in men, which may be explained by cancer type., Conclusions: Our results extend studies in breast and prostate cancer to show worse objective and patient-reported physical function outcomes in older adults with a range of cancer types compared to those without a cancer history. Moreover, these burdens seem to disproportionately affect older adult women, underscoring the need for interventions to address functional limitations and prevent further health consequences of cancer and its treatment., (© 2023 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Introduction: Balance decrements and increased fall risk in older cancer survivors have been attributed to chemotherapy-induced peripheral neuropathy (CIPN). Cognition is also affected by chemotherapy and may be an additional contributing factor to poor balance through changes in executive functioning. We examined the association of executive function with balance and falls in older cancer survivors who had been treated with chemotherapy., Materials and Methods: Fifty cancer survivors (aged 65.6 ± 11.5 years; 88% female) who were all treated with chemotherapy were included in this cross-sectional study at a tertiary medical center. Executive function was measured by Trails-B, Stroop, and rapid reaction accuracy, a measure emphasizing rapid inhibitory function. Balance was measured by five sit-to-stand time (5STS), repetitions of sit-to-stand in thirty seconds (STS30), and unipedal stance time (UST), which was the primary balance outcome measure. Self-reported falls in the past year were also recorded and was a secondary outcome. Bivariate analyses were conducted between executive function measures and balance variables. Multivariable models were constructed for UST and falls outcomes and included covariates of age and chemotherapy induced peripheral neuropathy status., Results: Pearson correlations demonstrated significant relationships between two executive function measures (rapid reaction accuracy, Trails-B) and all the balance measures assessed (UST, STS30, and 5STS). Rapid reaction accuracy correlations were stronger than Trails-B. The Stroop measure correlated solely with UST. In multivariable models, rapid reaction accuracy was associated with better UST (standardized regression coefficient: 64.1, p < 0.01), decreased any fall (odds ratio = 0.000901, p = 0.04), and decreased recurrent falls (odds ratio = 0.0000044, p = 0.01). The interaction of CIPN with the inhibitory measures in the prediction of balance was not significant., Discussion: Measures of executive function were associated with balance, but among the executive function tests, rapid reaction accuracy had the strongest correlations to balance and was independently associated with falls. The findings suggest that executive function should be considered when assessing fall risk and developing interventions intended to reduce fall risk in older chemotherapy-treated cancer survivors., Competing Interests: Declaration of Competing Interest BLM, KM, JM, NK, JAS, HC, MKH, RR, MR, CR, JKR, NK report no conflicts of interest with the current manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Brain gray matter (GM) reductions have been reported after breast cancer chemotherapy, typically in small and/or cross-sectional cohorts, most commonly using voxel-based morphometry (VBM). There has been little examination of approaches such as deformation-based morphometry (DBM), machine-learning-based brain aging metrics, or the relationship of clinical and demographic risk factors to GM reduction. This international data pooling study begins to address these questions. Participants included breast cancer patients treated with (CT+, n = 183) and without (CT-, n = 155) chemotherapy and noncancer controls (NC, n = 145), scanned pre- and post-chemotherapy or comparable intervals. VBM and DBM examined GM volume. Estimated brain aging was compared to chronological aging. Correlation analyses examined associations between VBM, DBM, and brain age, and between neuroimaging outcomes, baseline age, and time since chemotherapy completion. CT+ showed longitudinal GM volume reductions, primarily in frontal regions, with a broader spatial extent on DBM than VBM. CT- showed smaller clusters of GM reduction using both methods. Predicted brain aging was significantly greater in CT+ than NC, and older baseline age correlated with greater brain aging. Time since chemotherapy negatively correlated with brain aging and annual GM loss. This large-scale data pooling analysis confirmed findings of frontal lobe GM reduction after breast cancer chemotherapy. Milder changes were evident in patients not receiving chemotherapy. CT+ also demonstrated premature brain aging relative to NC, particularly at older age, but showed evidence for at least partial GM recovery over time. When validated in future studies, such knowledge could assist in weighing the risks and benefits of treatment strategies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We aimed to examine exercise intensity among older adults participating from home in remotely delivered EnhanceFitness (Tele-EF). Exercise intensity was assessed through Fitbit-measured heart rate and the Borg 10-point rating of perceived exertion over 1 week of a 16-week exercise program. Outcomes included mean minutes spent at or above the heart rate reserve calculated threshold for moderate intensity and mean rating of perceived exertion. Pearson and Spearman rank correlations were used to examine associations between baseline characteristics with exercise intensity. During the 60-min classes, the 55 participants achieved moderate intensity for a mean of 21.0 min (SD = 13.5) and had a mean rating of perceived exertion of 4.9 (SD = 1.2). There were no significant associations between baseline characteristics and exercise intensity. Older adults can achieve sustained moderate-intensity exercise during Tele-EF supervised classes. Baseline physical function, physical activity, and other health characteristics did not limit ability to exercise at a moderate intensity, though further investigation is warranted.

Virotherapy is a promising, novel form of cancer immunotherapy currently being investigated in pre-clinical and clinical settings. While generally well-tolerated, the anti-tumor potency of oncolytic virus-based monotherapies needs to be improved further. One of the major factors limiting the replication efficiency of oncolytic viruses are the antiviral defense pathways activated by tumor cells. In this study, we have designed and validated a universal expression cassette for artificial microRNAs that can now be adapted to suppress genes of interest, including potential resistance factors. Transcripts are encoded as a primary microRNA for processing via the predominantly nuclear RNase III Drosha. We have engineered an oncolytic measles virus encoding this universal expression cassette for artificial microRNAs. Virally encoded microRNA was expressed in the range of endogenous microRNA transcripts and successfully mediated target protein suppression. However, absolute expression levels of mature microRNAs were limited when delivered by an oncolytic measles virus. We demonstrate that measles virus, in contrast to other cytosolic viruses, does not induce translocation of Drosha from the nucleus into the cytoplasm, potentially resulting in a limited processing efficiency of virus-derived, cytosolically delivered artificial microRNAs. To our knowledge, this is the first report demonstrating functional expression of microRNA from oncolytic measles viruses potentially enabling future targeted knockdown, for instance of antiviral factors specifically in tumor cells.

Executive function (EF) impacts behavior associated with health outcomes. EF can be measured using self-report and/or performance measures, but the correlations between these types of measures are mixed in the extant literature. This study examined self-report and performance-based measures of EF using data from 6 studies, including community and clinical populations (410 participants, ages 19-80, 71% female). Partial correlations revealed significant relationships between performance on the Trail making, Delay Discounting, and Stop Signal tasks with self-reported EF ( p < .006 after controlling for age). Mood scores were significantly related to all self-reported domains of EF ( p < .0001), and mood and EF scores were correlated over time. When also controlling for mood, correlations between delay discounting and stop signal tasks with self-reported EF remained significant ( p < .006). Finally, examining EF scores in participants with and without clinically elevated mood scores showed a wider distribution of self-reported EF scores among those with clinically elevated mood symptoms than among those without. We conclude that self-reported EF is associated with tasks measuring delay discounting and response inhibition in our large, heterogenous population and that assessing EF may be particularly important for those with high levels of mood symptoms.

Purpose: Cyberattacks targeting health care organizations are becoming more frequent and affect all aspects of care delivery. Cancer care is particularly susceptible to major disruptions because of the potential of immediate and long-term consequences for patients who often rely on timely diagnostic testing and regular administration of systemic therapy in addition to other local treatment modalities to cure or control their diseases. On October 28, 2020, a cyberattack was launched on the University of Vermont Health Network with wide-ranging consequences for oncology, including loss of access to all network intranet servers, e-mail communications, and the electronic medical record (EMR)., Methods: This review details the immediate challenges faced by hematology and oncology during the cyberattack. The impact and response on inpatient, outpatient, and special patient populations are described. Steps that other academic- and community-based oncology practices can take to lessen the brunt of such an assault are suggested., Results: The two areas of immediate impact after the cyberattack were communications and lack of EMR access. The oncology-specific impact included loss of the individualized EMR chemotherapy plan templates and electronic safeguards built into multistep treatment preparation and delivery. With loss of access to schedules, basic patient information, encrypted communications platforms and radiology, and laboratory and pharmacy services, clinical outpatient care delivery was reduced by 40%. The infusion visit volume dropped by 52% in the first week and new patients could not access necessary services for timely diagnostic evaluation, requiring the creation of command centers to oversee ethical and transparent triage and allocation of systemic therapies and address new patient referrals. This included appropriate transfer of patients to alternate sites to minimize delays. Inpatient care including transitions of care was particularly challenging and addressing patient populations whose survival might be affected by delays in care., Conclusion: Oncology health care leaders and providers should be aware of the potential impact of a cyberattack on cancer care delivery and preventively develop processes to mitigate the impact., Competing Interests: Steven AdesResearch Funding: Lilly, EMD Serono Alissa A. ThomasResearch Funding: Novocure, Spectrum Pharmaceuticals, Spectrum Pharmaceuticals Julian SpragueStock and Other Ownership Interests: Gilead Sciences, Johnson and Johnson, Merk and Company, Roche/Genentech, Pfizer Peter A. KaufmanStock and Other Ownership Interests: AmgenHonoraria: Lilly, Polyphor, Macrogenics, EisaiConsulting or Advisory Role: Polyphor, Roche/Genentech, Lilly, Eisai, Macrogenics, Pfizer, Merck, AstraZenecaSpeakers' Bureau: LillyResearch Funding: Eisai, Polyphor, Roche/Genentech, Lilly, Novartis, Macrogenics, Pfizer, SanofiTravel, Accommodations, Expenses: Lilly, Polyphor, MacrogenicsNo other potential conflicts of interest were reported.

Purpose: Cancer therapy diminishes strength and physical function in cancer survivors. Whether oncology rehabilitation (OR) exercise training following therapy can correct these deficits, and whether its effectiveness differs by age, is not clear. We examine the utility of a clinically based, 12-week, combined aerobic and resistance training intervention on muscle strength and physical function in two age groups of cancer survivors., Methods: Strength and physical function measures were assessed in middle-aged (45 to 64 years) and older (≥ 65 years) patients following treatment for stage 0-III cancer before and after the OR training program., Results: Older patients had lower physical function compared to middle-aged patients across a range of subjective and objective measures at baseline, and exercise improved all indices of physical function and strength in both age groups. Compared to the middle-aged individuals, older participants tended to have less improvement leg strength and the 5 time sit to stand (5TSTS) test as a result of OR. In models predicting post-intervention measures, older age contributed to less improvement in walking distance and power as well as the 5TSTS test., Conclusion: Prior to beginning the OR exercise program, middle-aged patients had higher physical function compared to older patients. However, a 12-week aerobic and resistance training intervention improved physical function across both age groups, although older age did limit responsiveness in some physical function measures. The physical function and strength of middle-aged and older cancer survivors improve in response to an exercise-based OR program after cancer treatment.

Exercise has numerous benefits for patients with cancer, but implementation is challenging because of practical and logistical hurdles. This study examined whether neuromuscular electrical stimulation (NMES) can serve as a surrogate for classic exercise by eliciting an exercise training response in skeletal muscle of women diagnosed with breast cancer undergoing chemotherapy. Patients ( n = 22) with histologically confirmed stage I, II, or III breast cancer scheduled to receive neoadjuvant or adjuvant chemotherapy were randomized to 8 wk of bilateral neuromuscular electrical stimulation (NMES; 5 days/wk) to their quadriceps muscles or control. Biopsy of the vastus lateralis was performed at baseline and after 8 wk of intervention to assess muscle fiber size, contractility, and mitochondrial content. Seventeen patients (8 control/9 NMES) completed the trial and were included in analyses. NMES promoted muscle fiber hypertrophy ( P < 0.001), particularly in fast-twitch, myosin heavy chain (MHC) IIA fibers ( P < 0.05) and tended to induce fiber type shifts in MHC II fibers. The effects of NMES on single-muscle fiber contractility were modest, and it was unable to prevent declines in the function in MHC IIA fibers. NMES did not alter intermyofibrillar mitochondrial content/structure but was associated with reductions in subsarcolemmal mitochondria. Our results demonstrate that NMES induces muscle fiber hypertrophy and fiber type shifts in MHC II fibers but had minimal effects on fiber contractility and promoted reductions in subsarcolemmal mitochondria. Further studies are warranted to evaluate the utility of NMES as an exercise surrogate in cancer patients and other conditions. NEW & NOTEWORTHY This is the first study to evaluate whether neuromuscular electrical stimulation (NMES) can be used as an exercise surrogate to improve skeletal muscle fiber size or function in cancer patients receiving treatment. We show that NMES promoted muscle fiber hypertrophy and fiber type shifts but had minimal effects on single-fiber contractility and reduced subsarcolemmal mitochondria.

Purpose: Physical activity minimizes the side effects of cancer; yet, participation rates among cancer survivors are low. Technological innovations are promoted as efficient means for communication and remote monitoring, but little is known about acceptability among female cancer survivors. The purpose of this study was to examine female cancer survivor perspectives on remote monitoring and communication to support independent, physical activity maintenance after completing a structured, facility-based program., Methods: Participants were 19 female cancer survivors (mean age 56.3) recruited after completing a 12-week exercise-based oncology rehabilitation program. Semi-structured interviews were conducted with participants following a 4-week pilot trial of a tailored text message, FitBit®, and health coach intervention to support independent physical activity maintenance. All interviews were audio-recorded and transcribed. Transcripts from the interviews were iteratively coded by two team members using a thematic analysis., Results: Participants reported acceptance and satisfaction with remote monitoring and communication. Emergent themes related to technology-based support for physical activity maintenance included the following: (1) accountability to a remote partner; (2) plan Bs, planning for barriers; (3) the habit cycle; (4) convenience through technology; and (5) reclaiming health ownership following a cancer diagnosis., Conclusions: Participants attributed physical activity maintenance to accountability enabled by technology. Communication based on remote monitoring was perceived as encouraging and not intrusive, during the transition to a home program., Implications for Cancer Survivors: This study highlights the importance of accountability and support for physical activity adherence and the positive role that technology can provide for female cancer survivors to regain control of health management.

Purpose: We aimed to determine the effect of a health coach, text message, and Fitbit intervention on moderate-to-vigorous physical activity (MVPA) maintenance in cancer survivors following a supervised exercise program compared to provision of a Fitbit alone., Methods: Participants were recruited during the last month of an exercise-based oncology rehabilitation program and randomly assigned to the full intervention (n = 34) or Fitbit-only control groups (n = 32). In total, 59 cancer survivors completed the program (81% female; mean age 61.4 ± 9.0). Group by time differences in accelerometer-measured MVPA was assessed using linear mixed models. Additionally, we examined mean weekly Fitbit-derived MVPA levels., Results: Intervention participants maintained weekly MVPA from pre- (295.7 ± 139.6) to post-intervention (322.0 ± 199.4; p = 0.37), whereas those in the Fitbit-only group had a significant decrease in MVPA (305.5 ± 181.1 pre vs 250.7 ± 166.5 post; p = 0.03, effect size 0.57). The intervention participants maintained recommended levels of MPVA for health benefits during the 8-week intervention, whereas the Fitbit-only control group did not., Conclusions: The findings demonstrate that a remote intervention delivered through health coaching, text messages, and Fitbit can promote maintenance of MVPA after a structured program for cancer survivors. However, use of a Fitbit alone was not sufficient to prevent expected decline in MVPA. Additional research is warranted to examine long-term impacts and efficacy in a more diverse population of cancer survivors., Implications for Cancer Survivors: Use of a wearable tracker alone may not be sufficient for exercise maintenance among cancer survivors after transition to an independent program. Additional planning for relapse prevention is recommended.

How breast cancer and its treatments affect skeletal muscle is not well defined. To address this question, we assessed skeletal muscle structure and protein expression in 13 women who were diagnosed with breast cancer and receiving adjuvant chemotherapy following tumor resection and 12 nondiseased controls. Breast cancer patients showed reduced single-muscle fiber cross-sectional area and fractional content of subsarcolemmal and intermyofibrillar mitochondria. Drugs commonly used in breast cancer patients (doxorubicin and paclitaxel) caused reductions in myosin expression, mitochondrial loss, and increased reactive oxygen species (ROS) production in C2C12 murine myotube cell cultures, supporting a role for chemotherapeutics in the atrophic and mitochondrial phenotypes. Additionally, concurrent treatment of myotubes with the mitochondrial-targeted antioxidant MitoQ prevented chemotherapy-induced myosin depletion, mitochondrial loss, and ROS production. In patients, reduced mitochondrial content and size and increased expression and oxidation of peroxiredoxin 3, a mitochondrial peroxidase, were associated with reduced muscle fiber cross-sectional area. Our results suggest that chemotherapeutics may adversely affect skeletal muscle in patients and that these effects may be driven through effects of these drugs on mitochondrial content and/or ROS production.

Purpose: The purpose of this study was to evaluate a new care model to reduce chemotherapy-induced neuropathic symptoms. Neuropathic symptom usual care was prospectively compared to an automated symptom-monitoring and coaching system, SymptomCare@Home (SCH), which included nurse practitioner follow-up triggered by moderate to severe symptoms., Methods: Patients beginning chemotherapy were randomized to usual care (UC) or to the SCH intervention. This sub-analysis included only taxane/platin therapies. Participants called the automated telephone symptom-monitoring system daily to report numbness and tingling. The monitoring system recorded patient-reported neuropathic symptom severity, distress, and activity interference on a 0-10 scale. UC participants were instructed to call their oncologist for symptom management. SCH participants with symptom severity of ≥ 4 received automated self-care strategies, and a nurse practitioner (NP) provided guideline-based care., Results: There were 252 participants, 78.6% of which were female. Mean age was 55.1 years. Mean follow-up was 90.2 ± 39.9 days (81.1 ± 40.3 calls). SCH participants had fewer days of moderate (1.8 ± 4.0 vs. 8.6 ± 17.3, p < 0.001) and severe chemotherapy-induced peripheral neuropathy symptoms (0.3 ± 1.0 vs. 1.1 ± 5.2, p = 0.006). SCH participants had fewer days with moderate and severe symptom-related distress (1.4 ± 3.7 vs. 6.9 ± 15.0, p < 0.001; 0.2 ± 0.9 vs. 1.5 ± 6.1, p = 0.001) and trended towards less activity interference (3.3 ± 1.9 vs. 3.8 ± 2.1, p = 0.08). Other neuropathic symptoms were addressed in 5.8-15.4% of SCH follow-up calls., Conclusions: The SCH system effectively identified neuropathic symptoms and their severity and, paired with NP follow-up, reduced symptom prevalence, severity, and distress compared to usual care.

Purpose: Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS., Methods: A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test., Results: Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population., Conclusion: A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Cancer survivors are at increased risk of chronic disease and diminished quality of life. The presence of overweight and obesity can exacerbate these health risks. Fortunately, even small weight losses have been found to produce clinically meaningful health outcomes. However, effective obesity treatment is difficult to access, and recently, efforts have been made to disseminate interventions using eHealth or distantly delivered technology. This review aims to focus on the efficacy and limitations of these technologies for female cancer survivors. Suggestions are also provided to encourage further meaningful work in this area.

Purpose: Physical activity is known to minimize the long-term side effects of cancer treatment. Yet, rates of physical activity participation by cancer survivors are significantly lower compared to the general population. The purpose of this pilot study was to examine the efficacy, feasibility, and acceptability of a technology-based intervention to promote maintenance of physical activity after completing an exercise-based oncology rehabilitation program., Methods: The pre-post 4-week intervention included support delivered through tailored text messages, Fitbit® self-monitoring, and brief health coaching sessions. The primary outcome measure was accelerometer-assessed physical activity levels. Self-efficacy, self-regulation, social support, fatigue, sleep disturbance, depression, and Fitbit® step counts were assessed as secondary outcomes., Results: Twenty-four participants (20 females; mean age = 57.9 years ± 10.4) completed the intervention. Mean daily step counts and weekly minutes of moderate-to-vigorous intensity physical activity were maintained after the intervention, as compared to baseline levels achieved at the end of 12 weeks of exercise-based oncology rehabilitation. Both self-regulation (goal setting, relapse prevention) and fatigue severity increased significantly post intervention as compared to baseline (p = 0.05 and p = 0.02, respectively). Qualitative responses demonstrated overall satisfaction with intervention components., Conclusions: Results demonstrate efficacy of the intervention for maintenance of physical activity levels achieved during exercise-based oncology rehabilitation. Low attrition and high satisfaction provide evidence for both the acceptability and feasibility of the intervention components. Exercise interventions post oncology treatment provide multiple benefits for cancer survivors, yet continued maintenance after program completion is challenging. Technological options offer low-cost, accessible modes to deliver continued monitoring and support beyond traditional facility-based programs.

The combination of personalized therapy with immunotherapy might lead to rapid complete remission in patients who are too sick to be eligible for clinical trials. We report 2 such extraordinary responders. A discussion on the use and purpose of clinical trials in this new era of very active anticancer drug discovery concludes that a paradigm shift is urgently needed., (© 2016 S. Karger AG, Basel.)

Background & Aims: Cancer patients frequently experience weight loss, with negative consequences for functionality and prognosis. The extent to which muscle atrophy contributes to weight loss, however, is not clear, as few studies have directly measured muscle fiber morphology in cancer patients., Methods: Whole body and regional tissue composition were measured, along with the cross-sectional area (CSA) and fiber type of mechanically-isolated, single muscle fibers, in 19 cancer patients (8 with a history of weight loss, 11 weight-stable) and 15 non-diseased controls., Results: Whole body fat mass was reduced in cancer patients with a history of weight loss, but no differences in whole body or leg fat-free mass were apparent. In contrast, reductions (∼20%) in single muscle fiber CSA were found in both slow-twitch, myosin heavy chain (MHC) I and fast-twitch, MHC IIA fibers in both weight-stable patients and those with a history of weight loss. Fiber type distribution showed a shift towards a fast-twitch phenotype compared to controls, which may preserve muscle function in cancer patients despite atrophy, as positive relationships were found between the fractions of hybrid MHC IIAX and I/IIA fibers and 6-min walk performance., Conclusions: Our results suggest that, although not apparent from whole body or regional measurements, cancer is associated with reduced skeletal muscle fiber size independent of weight loss history and a shift towards fast-twitch fibers, phenotypes that resemble adaptations to muscle disuse., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose: This is a case study of an aerobically trained, multisport, female athlete (age = 39) diagnosed with stage IIIc human epidermal growth factor receptor 2 positive breast cancer. The focus of the study is on measures of cardiorespiratory fitness (V˙O2peak) through the course of cancer therapy., Methods: A symptom-limited cardiopulmonary exercise tolerance test was performed to determine V˙O2peak. The tests were performed at five different time points: 1) at diagnosis of breast cancer and before initiating chemotherapy, 2) after completion of chemotherapy (5 months postdiagnosis), 3) 2.5 months after bilateral mastectomy surgery (9 months postdiagnosis), 4) immediately after radiation therapy (11 months postdiagnosis), and 5) recovery (32 months postdiagnosis)., Results: At diagnosis and before initiating chemotherapy, V˙O2peak was 50.1 mL O2·min·kg. The most precipitous decline in fitness, approximately 14%, was observed from initial diagnosis through the completion of chemotherapy. The subject regained 9% of her fitness after chemotherapy, despite an intervening mastectomy surgery. Radiation therapy was associated with an approximately 4% decline in fitness from her postmastectomy surgery value. Ultimately, 32 months after diagnosis and 22 months after the completion of radiation therapy, the subject was able to regain pretreatment fitness levels., Conclusion: The results of the case study describe the effects of undergoing extensive breast cancer therapy on measures of V˙O2peak for a highly aerobically trained, multisport athlete. In this case, exercise training reversed the decrement in measured V˙O2peak that occurred during cancer therapy.

Background: The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors., Methods: Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression., Results: DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups., Conclusions: Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2810-2818. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that comprises approximately 20% of new breast cancer diagnoses. DCIS is predominantly detected by screening mammography prior to the development of any clinical symptoms. Prognosis following a DCIS diagnosis is excellent, due to both the availability of effective treatments and the frequently benign nature of the disease. However, a DCIS diagnosis and its treatment have psychological and physical impacts that often lead to adverse changes in health-related behaviors, including changes in physical activity, body weight, alcohol intake, and smoking, which may represent a greater threat to the woman's overall health than the DCIS itself. Depending on age at diagnosis, women diagnosed with DCIS are 3-13 times more likely to die from non-breast cancer related causes, such as cardiovascular disease, than from breast cancer. Thus, the maintenance and improvement of healthy behaviors that influence a variety of outcomes after diagnosis may warrant increased attention during DCIS management. This may also represent an important opportunity to promote the adoption of healthy behaviors, given that DCIS carries the psychological impact of a cancer diagnosis but also a favorable prognosis. Particular focus is needed to address these issues in vulnerable patient subgroups with pre-existing higher rates of unhealthy behaviors and demonstrated health disparities., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The pathophysiology of cancer cachexia remains complex. A comprehensive literature search was performed up to April 2013 using PubMed, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and the Google search engine. In this review, we focus on the different mediators of impaired anabolism and upregulated catabolism that alter the skeletal muscle homeostasis resulting in the wasting of cancer cachexia. We present recent evidence of targeted treatment modalities from clinical trials along with their potential mechanisms of action. We also report on the most current evidence from randomized clinical trials using multimodal treatments in patients with cancer cachexia, but also the evidence from head and neck cancer-specific trials. A more complete understanding of the pathophysiology of the syndrome may lead to more effective targeted therapies and improved outcomes for patients., (© 2015 Wiley Periodicals, Inc.)

Cachexia is a profoundly debilitating wasting syndrome that affects patients with head and neck cancer and often contributes to their demise. A comprehensive literature search was performed up to April 2013 using PubMed, the Cochrane Library, CINAHL, and the Google search engine. For the meta-analyses, pooled prevalence estimates were calculated with a confidence interval of 95% (95% CI) by using random effects modeling. In this review, we outlined the unique challenges of cancer cachexia among patients with head and neck cancer by reviewing its impacts on quality of life (QOL), morbidity, and mortality. We explored the prevalence of different clinical markers of cachexia at the time of diagnosis and before and after treatment. Finally, we present updates regarding the diagnosis of cancer cachexia and recent findings, such as cardiac dysfunction that warrant clinical attention to more carefully identify patients at risk and potentially lead to better outcomes., (© 2014 Wiley Periodicals, Inc.)

Background: There is emerging evidence that adjuvant treatments for breast cancer negatively impact cardiorespiratory fitness (CRF) or Vo2max, a key predictor of cardiovascular risk. Although a number of studies have measured CRF in breast cancer patients, there is currently limited data regarding expected CRF values in this patient population. Given that CRF is a poor prognostic sign and recently highlighted as a key measure to standardize by the American Heart Association, we sought to review the available literature on CRF among breast cancer patients., Methods and Results: We identified 27 clinical trials and observational studies measuring Vo2max in the pre- and post-adjuvant treatment setting for breast cancer. We compared Vo2max before to Vo2max after adjuvant therapy and compared Vo2max in female breast cancer patients with Vo2max in healthy controls., Conclusions: We found that CRF was substantially lower in women with a history of breast cancer compared with healthy women and this was most pronounced among breast cancer patients in the post-adjuvant setting. We conclude that knowledge of normative CRF values is critical to tailor appropriately timed exercise interventions in breast cancer patients susceptible to low CRF and subsequent cardiovascular risk.

Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, 1 month after, and 1 year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity 1 month after chemotherapy that partially returned to baseline at 1 year in the dorsal attention network. Decreased connectivity was seen in the default mode network at 1 month and 1 year following chemotherapy. In addition, increased subjective memory complaints were noted at 1 month and 1 year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment.

Background: Controversy remains regarding the frequency of screening mammography. Women with different risks for developing breast cancer because of body mass index (BMI) may benefit from tailored recommendations., Objective: To determine the impact of mammography screening interval for women who are normal weight (BMI < 25), overweight (BMI 25-29.9), or obese (BMI ≥ 30), stratified by menopausal status., Design: Two cohorts selected from the Breast Cancer Surveillance Consortium. Patient and mammography data were linked to pathology databases and tumor registries., Participants: The cohort included 4,432 women aged 40-74 with breast cancer; the false-positive analysis included a cohort of 553,343 women aged 40-74 without breast cancer., Main Measures: Stage, tumor size and lymph node status by BMI and screening interval (biennial vs. annual). Cumulative probability of false-positive recall or biopsy by BMI and screening interval. Analyses were stratified by menopausal status., Key Results: Premenopausal obese women undergoing biennial screening had a non-significantly increased odds of a tumor size > 20 mm relative to annual screeners (odds ratio [OR] = 2.07; 95 % confidence interval [CI] 0.997 to 4.30). Across all BMI categories from normal to obese, postmenopausal women with breast cancer did not present with higher stage, larger tumor size or node positive tumors if they received biennial rather than annual screening. False-positive recall and biopsy recommendations were more common among annually screened women., Conclusion: The only negative outcome identified for biennial vs. annual screening was a larger tumor size (> 20 mm) among obese premenopausal women. Since annual mammography does not improve stage at diagnosis compared to biennial screening and false-positive recall/biopsy rates are higher with annual screening, women and their primary care providers should weigh the harms and benefits when deciding on annual versus biennial screening.

Importance: Controversy exists about the frequency women should undergo screening mammography and whether screening interval should vary according to risk factors beyond age., Objective: To compare the benefits and harms of screening mammography frequencies according to age, breast density, and postmenopausal hormone therapy (HT) use., Design: Prospective cohort., Setting: Data collected January 1994 to December 2008 from mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium (BCSC) mammography registries., Participants: Data were collected prospectively on 11,474 women with breast cancer and 922,624 without breast cancer who underwent mammography at facilities that participate in the BCSC., Main Outcomes and Measures: We used logistic regression to calculate the odds of advanced stage (IIb, III, or IV) and large tumors (>20 mm in diameter) and 10-year cumulative probability of a false-positive mammography result by screening frequency, age, breast density, and HT use. The main predictor was screening mammography interval., Results: Mammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of women's breast density or HT use. Among women aged 40 to 49 years with extremely dense breasts, biennial mammography vs annual is associated with increased risk of advanced-stage cancer (odds ratio [OR], 1.89; 95% CI, 1.06-3.39) and large tumors (OR, 2.39; 95% CI, 1.37-4.18). Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibroglandular densities (30.7% and 21.9%, respectively) or fatty breasts (17.4% and 12.1%, respectively)., Conclusions and Relevance: Women aged 50 to 74 years, even those with high breast density or HT use, who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography. When deciding whether to undergo mammography, women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advanced-stage disease but the cumulative risk of false-positive results is high.

Many patients with cancer experience physical disability following diagnosis, although little is known about the mechanisms underlying these functional deficits. To characterize skeletal muscle adaptations to cancer in humans, we evaluated skeletal muscle structure and contractile function at the molecular, cellular, whole-muscle, and whole-body level in 11 patients with cancer (5 cachectic, 6 noncachectic) and 6 controls without disease. Patients with cancer showed a 25% reduction in knee extensor isometric torque after adjustment for muscle mass (P < 0.05), which was strongly related to diminished power output during a walking endurance test (r = 0.889; P < 0.01). At the cellular level, single fiber isometric tension was reduced in myosin heavy chain (MHC) IIA fibers (P = 0.05) in patients with cancer, which was explained by a reduction (P < 0.05) in the number of strongly bound cross-bridges. In MHC I fibers, myosin-actin cross-bridge kinetics were reduced in patients, as evidenced by an increase in myosin attachment time (P < 0.01); and reductions in another kinetic parameter, myosin rate of force production, predicted reduced knee extensor isometric torque (r = 0.689; P < 0.05). Patients with cancer also exhibited reduced mitochondrial density (-50%; P < 0.001), which was related to increased myosin attachment time in MHC I fibers (r = -0.754; P < 0.01). Finally, no group differences in myofilament protein content or ultrastructure were noted that explained the observed functional alterations. Collectively, our results suggest reductions in myofilament protein function as a potential molecular mechanism contributing to muscle weakness and physical disability in human cancer.

Background Uncertainty exists about the appropriate use of screening mammography among older women because comorbid illnesses may diminish the benefit of screening. We examined the risk of adverse tumor characteristics and false positive rates according to screening interval, age, and comorbidity. Methods From January 1999 to December 2006, data were collected prospectively on 2993 older women with breast cancer and 137 949 older women without breast cancer who underwent mammography at facilities that participated in a data linkage between the Breast Cancer Surveillance Consortium and Medicare claims. Women were aged 66 to 89 years at study entry to allow for measurement of 1 year of preexisting illnesses. We used logistic regression analyses to calculate the odds of advanced (IIb, III, IV) stage, large (>20 millimeters) tumors, and 10-year cumulative probability of false-positive mammography by screening frequency (1 vs 2 years), age, and comorbidity score. The comorbidity score was derived using the Klabunde approximation of the Charlson score. All statistical tests were two-sided. Results Adverse tumor characteristics did not differ statistically significantly by comorbidity, age, or interval. Cumulative probability of a false-positive mammography result was higher among annual screeners than biennial screeners irrespective of comorbidity: 48.0% (95% confidence interval [CI] = 46.1% to 49.9%) of annual screeners aged 66 to 74 years had a false-positive result compared with 29.0% (95% CI = 28.1% to 29.9%) of biennial screeners. Conclusion Women aged 66 to 89 years who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners, regardless of comorbidity.

The progression of breast cancer from early-stage to metastatic disease results from a series of events during which malignant cells invade and travel within the bloodstream to distant sites, leading to a clonogenic accumulation of tumor cells in non-breast tissue. While mechanistically complex, an emerging literature supports hemostatic elements as an important patient factor that facilitates the metastatic potential of breast cancer. Hemostatic elements involved include platelets, coagulation, and fibrinolysis. Key steps in breast tumor progression, including cellular transformation, proliferation, tumor cell survival, and angiogenesis, can be mediated by components of the hemostatic system. Thus, the hemostatic system provides potential targets for novel therapeutic approaches to breast cancer therapy with drugs in current use and in development. The present article provides a comprehensive overview of the evidence and mechanisms supporting the roles played by platelets, coagulation activation, and the fibrinolytic system in breast cancer progression.

Cancer is a physically disabling condition. Functional disability, defined as an inability or impaired ability to perform simple tasks of daily life, afflicts a large majority of the cancer population and dramatically impacts patient well-being, negatively affecting treatment decisions, quality of life, and clinical outcomes. Our current understanding of the fundamental mechanisms underlying physical disability in cancer patients, however, is limited. This review will evaluate how cancer and cancer treatments and their pathological sequelae alter skeletal muscle structure and function to promote functional disability. Briefly, factors associated with cancer and its treatment can diminish skeletal muscle size and contractile function, which lead to a reduced physiological capacity for work and, in turn, functional disability. We outline the clinical evidence for the involvement of each of these factors in disability in cancer patients and then review structural and functional evidence at various anatomic levels to explore the tissue, cellular, and molecular mechanisms underlying cancer-related disability.

Many causes of esophagitis exist in immunocompromised patients. Uncommon pathogens must be considered to facilitate timely and appropriate therapy. A limited number of cases of esophageal actinomycosis have been reported. This report describes an unusual case of esophageal actinomycosis in a patient with persistent dysphagia. The broad differential may have delayed definitive diagnosis in the case study patient. Biopsy and culture are essential for accurate diagnosis. Although actinomycosis is a rare disease, it should be included in the differential diagnosis of patients presenting with oral or esophageal complaints. It may also be considered as an opportunistic infection in immunocompromised patients. The treatment of choice is parenteral penicillin G, 18 to 24 million units for 2 to 6 weeks followed by oral therapy for 6-12 months.

Myocardial infarction is a common life-threatening condition. Multiple agents can be used to treat acute coronary syndrome (ACS). These therapeutic agents pose potential life-threatening complications when used outside the realm of the acute coronary syndrome. Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder, occurring in 1 in 500 individuals, which may mimic ACS. The hypertrophy most typically involves the septum in patients with HCM. As many as 25% of Japanese patients with HCM have predominately apical involvement. Apical hypertrophic cardiomyopathy (AHC) occurs in only 1 to 2% of the non-Japanese population. Despite its low incidence, physicians caring for patients with chest pain need to consider AHC in their differential diagnosis. We present the case of a patient with chest pain and electrocardiographic changes suggestive of ACS who was later found to have AHC.

A study was conducted to compare the pharmacokinetic profile of three oral magnesium supplements--magnesium chloride solution, slow-release magnesium chloride tablets, and magnesium gluconate tablets--at 16 mmol/dose. Twelve healthy normomagnesemic subjects were evaluated during an initial baseline study, followed by three magnesium supplementation studies. Supplements were administered in a randomized, crossover fashion at weekly intervals. During each of the four trials, subjects followed the same routines and consumed identical diets. Magnesium concentrations were measured in urine samples collected from 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours. Intraleukocyte, total serum, and ultrafiltrable magnesium were measured in blood samples drawn at 0, 1, 2, 3, 4, 8, 12, and 24 hours. Compared with baseline, 24-hour urinary magnesium excretion significantly increased (P < 0.05) after the administration of the magnesium chloride solution and also increased after the administration of the other supplements, but the difference was not significant. The 24-hour areas under the curve (AUCs) for total serum, ultrafiltrable, and leukocyte magnesium were greater after the administration of each of the supplements when compared with baseline, although the differences were not statistically significant. Differences in delta AUCs (supplement AUC minus baseline AUC) for total magnesium, ultrafiltrable magnesium, and 24-hour urinary magnesium excretion were statistically different from zero or between supplements. Statistically significant differences (P < 0.05) in total serum, ultrafiltrable, and leukocyte magnesium concentrations were observed at various time points. These results suggest that there were no major differences in the overall effect of these supplements on total serum, ultrafiltrable, and leukocyte magnesium concentrations but do reveal differences in the time-concentration profiles in magnesium levels in blood and urine among the three supplement forms.