Sandahl H. Nelson

Prolonged Nightly Fasting and Breast Cancer Prognosis

IMPORTANCE Rodent studies demonstrate that prolonged fasting during the sleep phase positively influences carcinogenesis and metabolic processes that are putatively associated with risk and prognosis of breast cancer. To our knowledge, no studies in humans have examined nightly fasting duration and cancer outcomes. OBJECTIVE To investigate whether duration of nightly fasting predicted recurrence and mortality among women with early-stage breast cancer and, if so, whether it was associated with risk factors for poor outcomes, including glucoregulation (hemoglobin A1c), chronic inflammation (C-reactive protein), obesity, and sleep. DESIGN, SETTING, AND PARTICIPANTS Data were collected from 2413 women with breast cancer but without diabetes mellitus who were aged 27 to 70 years at diagnosis and participated in the prospective Womens Healthy Eating and Living study between March 1, 1995, and May 3, 2007. Data analysis was conducted from May 18 to October 5, 2015. EXPOSURES Nightly fasting duration was estimated from 24-hour dietary recalls collected at baseline, year 1, and year 4. MAIN OUTCOMES AND MEASURES Clinical outcomes were invasive breast cancer recurrence and new primary breast tumors during a mean of 7.3 years of study follow-up as well as death from breast cancer or any cause during a mean of 11.4 years of surveillance. Baseline sleep duration was self-reported, and archived blood samples were used to assess concentrations of hemoglobin A1c and C-reactive protein. RESULTS The cohort of 2413 women (mean [SD] age, 52.4 [8.9] years) reported a mean (SD) fasting duration of 12.5 (1.7) hours per night. In repeated-measures Cox proportional hazards regression models, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76). Nightly fasting less than 13 hours was not associated with a statistically significant higher risk of breast cancer mortality (hazard ratio, 1.21; 95% CI, 0.91-1.60) or a statistically significant higher risk of all-cause mortality (hazard ratio, 1.22; 95% CI, 0.95-1.56). In multivariable linear regression models, each 2-hour increase in the nightly fasting duration was associated with significantly lower hemoglobin A1c levels (β = -0.37; 95% CI, -0.72 to -0.01) and a longer duration of nighttime sleep (β = 0.20; 95% CI, 0.14-0.26). CONCLUSIONS AND RELEVANCE Prolonging the length of the nightly fasting interval may be a simple, nonpharmacologic strategy for reducing the risk of breast cancer recurrence. Improvements in glucoregulation and sleep may be mechanisms linking nightly fasting with breast cancer prognosis.

Advance Care Planning and Palliative Care Integration for Patients Undergoing Hematopoietic Stem-Cell Transplantation

PURPOSE Advance care planning (ACP) in hematopoietic stem-cell transplantation (HSCT) is challenging, given the potential for cure despite increased morbidity and mortality risk.The aim of this study was to evaluate ACP and palliative care (PC) integration for patients who underwent HSCT. METHODS A retrospective analysis was conducted and data were extracted from electronic medical records of patients who underwent HSCT between January 2011 and December 2015. Patients who received more than one transplant and who were younger than 18 years of age were excluded. The primary objective was to determine the setting and specialty of the clinician who documented the initial and final code status. Secondary objectives included evaluation of advance directive and/or completion of the Physician Orders for Life-Sustaining Treatment form, PC consultation, hospice enrollment, and location of death. RESULTS The study sample comprised 39% (n = 235) allogeneic and 61% (n = 367) autologous HSCTs. All patients except one (n = 601) had code status documentation, and 99.2% (n = 596) were initially documented as full code. Initial and final code status documentation in the outpatient setting was 3% (n = 17) and 24% (n = 143), respectively. PC consultation occurred for 19% (n = 114) of HSCT patients, with 83% (n = 95) occurring in the hospital. Allogeneic transplant type and age were significantly associated with greater rates of advance directive and/or Physician Orders for Life-Sustaining Treatment completion. Most patients (85%, n = 99) died in the hospital, and few were enrolled in hospice (15%, n = 17). CONCLUSION To our knowledge, this is the largest single-center study of ACP and PC integration for patients who underwent HSCT. Code status documentation in the outpatient setting was low, as well as utilization of PC and hospice services.

Randomized controlled trial of increasing physical activity on objectively measured and self‐reported cognitive functioning among breast cancer survivors: The memory & motion study

Increasing physical activity can improve cognition in healthy and cognitively impaired adults; however, the benefits for cancer survivors are unknown. The current study examined a 12‐week physical activity intervention, compared with a control condition, on objective and self‐reported cognition among breast cancer survivors.

Technology- and Phone-Based Weight Loss Intervention Pilot RCT in Women at Elevated Breast Cancer Risk

INTRODUCTION For women with an increased breast cancer risk, reducing excess weight and increasing physical activity are believed to be important approaches for reducing their risk. This study tested a weight loss intervention that combined commercially available technology-based self-monitoring tools with individualized phone calls. DESIGN Women were randomized to a weight loss intervention arm (n=36) or a usual care arm (n=18). SETTING/PARTICIPANTS Participants were women with a BMI ≥ 27.5 kg/m2 and elevated breast cancer risk recruited from the mammography clinic at the Moores Cancer Center at the University of California San Diego. INTERVENTION Intervention participants used the MyFitnessPal website and phone app to monitor diet and a Fitbit to monitor physical activity. Participants received 12 standardized coaching calls with trained counselors over 6 months. Usual care participants received the U.S. Dietary Guidelines for Americans at baseline and two brief calls over the 6 months. MAIN OUTCOME MEASURES Weight and accelerometer-measured physical activity were assessed at baseline and 6 months. Data were collected in San Diego, CA, from 2012 to 2014 and analyzed in 2015. RESULTS Participants (n=54) had a mean age of 59.5 (SD=5.6) years, BMI of 31.9 (SD=3.5), and a mean Gail Model score of 2.5 (SD=1.4). At 6 months, intervention participants had lost significantly more weight (4.4 kg vs 0.8 kg, p=0.004) and a greater percentage of starting weight (5.3% vs 1.0%, p=0.005) than usual care participants. Across arms, greater increases in moderate-to-vigorous physical activity resulted in greater weight loss (p=0.01). CONCLUSIONS Combining technology-based self-monitoring tools with phone counseling supported weight loss over 6 months in women at increased risk for breast cancer.

Statistical approaches to account for missing values in accelerometer data: Applications to modeling physical activity

Physical inactivity is a recognized risk factor for many chronic diseases. Accelerometers are increasingly used as an objective means to measure daily physical activity. One challenge in using these devices is missing data due to device nonwear. We used a well-characterized cohort of 333 overweight postmenopausal breast cancer survivors to examine missing data patterns of accelerometer outputs over the day. Based on these observed missingness patterns, we created psuedo-simulated datasets with realistic missing data patterns. We developed statistical methods to design imputation and variance weighting algorithms to account for missing data effects when fitting regression models. Bias and precision of each method were evaluated and compared. Our results indicated that not accounting for missing data in the analysis yielded unstable estimates in the regression analysis. Incorporating variance weights and/or subject-level imputation improved precision by >50%, compared to ignoring missing data. We recommend that these simple easy-to-implement statistical tools be used to improve analysis of accelerometer data.

The association of the c-reactive protein inflammatory biomarker with breast cancer incidence and mortality in the women's health initiative

Purpose: To examine associations of prediagnosis high-sensitivity C-reactive protein (hsCRP) with breast cancer incidence and postdiagnosis survival and to assess whether associations are modified by body mass index (BMI). Methods: A prospective analysis of the Womens Health Initiative was conducted among 17,841 cancer-free postmenopausal women with baseline hsCRP measurements. Cox proportional hazards models were used to examine associations between hsCRP concentrations and (i) breast cancer risk (n cases = 1,114) and (ii) all-cause mortality after breast cancer diagnosis. HRs are per 1 SD in log hsCRP. Results: hsCRP was not associated with breast cancer risk overall [HR = 1.05; 95% confidence interval (CI), 0.98–1.12]; however, an interaction between BMI and hsCRP was observed (Pinteraction = 0.02). A 1 SD increase in log hsCRP was associated with 17% increased breast cancer risk (HR = 1.17; 95% CI, 1.03–1.33) among lean women (BMI < 25), whereas no association was observed among overweight/obese (BMI ≥ 25) women. Prediagnosis hsCRP was not associated with overall mortality (HR, 1.04; 95% CI, 0.88–1.21) after breast cancer diagnosis; however, an increased mortality risk was apparent among leaner women with higher hsCRP levels (HR, 1.39, 95% CI, 1.03–1.88). Conclusions: Prediagnosis hsCRP levels are not associated with postmenopausal breast cancer incidence or survival overall; however, increased risks are suggested among leaner women. The observed effect modification is in the opposite direction of a previous case–control study finding and warrants further investigation. Impact: Associations of higher CRP levels with incident breast cancer and survival after breast cancer may depend on BMI. Cancer Epidemiol Biomarkers Prev; 26(7); 1100–6. ©2017 AACR.

Advance care planning and palliative care consultation for stem cell transplant patients.

113 Background: Advance care planning (ACP) in stem cell transplantation (SCT) is particularly challenging given the potential for cure for patients with blood cancers despite an increased risk of suffering and even death. Data regarding ACP and palliative care (PC) integration in SCT is limited. METHODS A retrospective chart review was conducted of patients with hematologic malignancies who underwent SCT at UCSD from January 2011 to December 2015. The primary objective was to determine the medical discipline of the initial and last code status documentation. Secondary objectives included evaluation of AD and/or POLST completion, PC consultation, hospice enrollment, and location of death. Data were compiled from a single electronic medical record and descriptive statistical analyses performed. RESULTS A total of 633 SCT were performed from 2011 to 2015 including 39% (n = 245) allogeneic and 61% (n = 388) autologous transplants (n = 29 patients had 2 transplants). Mean age of SCT patients was 55 years (±13). All but one (n = 632) had code status documentation, and 0.8% (n = 5) were initially DNR. The initial code status was documented outpatient for 3% (n = 17), and by the primary SCT physician for 1 patient. The final code status was documented outpatient for 22% (n = 14), and by the primary SCT physician for 0.9% (n = 6). Nearly half (44%, n = 279) had an AD and/or POLST completed. PC consultation occurred for 19% (n = 121) with the majority (83%, n = 101) completed inpatient. PC consultation requests were made by the primary SCT physician (18%, n = 22), inpatient SCT team (68%, n = 82), critical care (8%, n = 10), or other (5%, n = 6).The most common reason for consultation was symptom management (80%, n = 94). As of January 2016, 20% (n = 127) of SCT patients died with a mean time from transplant of 312 days (± 317). Of those that died, the majority (83%, n = 106) died in the hospital, 15% (n = 19) were full code, 48% (n = 62) had an AD and/or POLST, and 14% (n = 18) were enrolled in hospice. CONCLUSIONS These single center data suggest ACP and PC integration in SCT is limited. Opportunities exist to expand integration to the outpatient setting and earlier in the course of illness.

Dimensions of sedentary behavior and objective cognitive functioning in breast cancer survivors

PurposeTo examine associations between dimensions of sedentary behavior and cognitive function in breast cancer survivors.MethodsSedentary behavior variables were measured using thigh-worn activPALs, and included total daily sitting time, time in long sitting bouts, sit-to-stand transitions, and standing time. Cognitive function was assessed using the NIH Toolbox Cognitive Domain. Separate multivariable linear regression models were used to examine associations between sedentary behavior variables with the cognitive domain scores of attention, executive functioning, episodic memory, working memory, and information processing speed.ResultsThirty breast cancer survivors with a mean age of 62.2 (SD = 7.8) years who were 2.6 (SD = 1.1) years since diagnosis completed study assessments. In multivariable linear regression models, more time spent standing was associated with faster information processing (b: 5.78; p = 0.03), and more time spent in long sitting bouts was associated with worse executive function (b: −2.82; p = 0.02), after adjustment for covariates. No other sedentary behavior variables were statistically significantly associated with the cognitive domains examined in this study.ConclusionsTwo important sedentary constructs that are amenable to intervention, including time in prolonged sitting bouts and standing time, may be associated with cognitive function in breast cancer survivors. More research is needed to determine whether modifying these dimensions of sedentary behavior will improve cognitive function in women with a history of breast cancer, or prevent it from declining in breast cancer patients.

Blood transfusions at end of life for stem cell transplant patients.

115 Background: Transfusions are an essential palliative tool in the stem cell transplant (SCT) population. Limited data exist regarding transfusion practices at end-of-life for SCT patients and whether these practices may limit enrollment in hospice. METHODS A retrospective chart review was conducted of deceased patients with hematologic malignancies who underwent SCT at an academic medical center from 2011 to 2015. The primary objective was to determine the difference between the dates of last transfusion and death in patients enrolled and not enrolled in hospice. A secondary objective was evaluation of the number of transfusions between groups. Data were compiled from a single electronic medical record. Descriptive analyses were performed. Days to last transfusion were analyzed using the Wilcoxon-Mann-Whitney test. Number of packed red blood cell (PRBC) transfusions and platelets transfusions on the last day were analyzed using Fisher and chi-squared tests, respectively. RESULTS A total of 633 SCT were performed from 2011 to 2015 including 39% (n = 245) allogeneic and 61% (n = 388) autologous transplants (n = 29 patients had 2 transplants). Mean ± SD age of SCT patients was 55 ± 13 years. As of January 2016, 20% (n = 119) of these SCT patients have died. Of those that died, 15% (n = 18) were enrolled in hospice. For SCT patients enrolled in hospice, the mean ± SD time of last blood transfusion from death was 42.3 ± 63.4 days, with mean ± SD 0.67 ± 0.77 units of PRBCs and 0.72 ± 0.75 units of platelets administered. For SCT patients not enrolled in hospice, the mean ± SD time of last blood transfusion from death was 14.2 ± 47.9 days, with mean±SD total 0.69 ± 1.03 units of PRBCs and 1.14 ± 1 units of platelets administered. Hospice patients had a statistically significant longer number of days until last blood transfusion compared to non-hospice patients (p < 0.001). There was no difference between SCT patients enrolled in hospice and not enrolled in PRBC transfusions (p = 0.069), but there was a significantly higher amount of platelet transfusions in patients not enrolled in hospice (p < 0.005). CONCLUSIONS This data suggests that time to last transfusion may be a significant obstacle for SCT patients when enrolling in hospice, but requires further validation.

Technology- and Phone-Based Weight Loss Intervention Pilot RCT in Women at Elevated Breast Cancer Risk - eScholarship

INTRODUCTION For women with an increased breast cancer risk, reducing excess weight and increasing physical activity are believed to be important approaches for reducing their risk. This study tested a weight loss intervention that combined commercially available technology-based self-monitoring tools with individualized phone calls. DESIGN Women were randomized to a weight loss intervention arm (n=36) or a usual care arm (n=18). SETTING/PARTICIPANTS Participants were women with a BMI ≥ 27.5 kg/m2 and elevated breast cancer risk recruited from the mammography clinic at the Moores Cancer Center at the University of California San Diego. INTERVENTION Intervention participants used the MyFitnessPal website and phone app to monitor diet and a Fitbit to monitor physical activity. Participants received 12 standardized coaching calls with trained counselors over 6 months. Usual care participants received the U.S. Dietary Guidelines for Americans at baseline and two brief calls over the 6 months. MAIN OUTCOME MEASURES Weight and accelerometer-measured physical activity were assessed at baseline and 6 months. Data were collected in San Diego, CA, from 2012 to 2014 and analyzed in 2015. RESULTS Participants (n=54) had a mean age of 59.5 (SD=5.6) years, BMI of 31.9 (SD=3.5), and a mean Gail Model score of 2.5 (SD=1.4). At 6 months, intervention participants had lost significantly more weight (4.4 kg vs 0.8 kg, p=0.004) and a greater percentage of starting weight (5.3% vs 1.0%, p=0.005) than usual care participants. Across arms, greater increases in moderate-to-vigorous physical activity resulted in greater weight loss (p=0.01). CONCLUSIONS Combining technology-based self-monitoring tools with phone counseling supported weight loss over 6 months in women at increased risk for breast cancer.