Introduction

Many breast cancer survivors experience problems with cognitive functioning that can persist years after treatment. Increasing physical activity has been shown to improve cognitive functioning in healthy and cognitively impaired adults, but has not yet been tested in cancer survivors. The primary aim of this randomized controlled trial is to examine the effects of a 3-month physical activity intervention compared to a waitlist Control arm on neuropsychological outcomes and subjective cognitive concerns in breast cancer survivors.

Methods

Eighty sedentary breast cancer survivors, self-reporting difficulties with cognition, will be randomized into an Exercise arm or Control arm. The Exercise arm includes an activity tracker (i.e., a Fitbit), phone calls, plus tailored and non-tailored email content. The Control arm will receive emails on women's health topics on the same schedule as the Exercise arm. Assessments conducted at baseline and 3 months include: neuropsychological testing, cognitive concerns and other aspects of quality of life, and 7 days of a hip-worn accelerometer. Participants will also provide fasting blood draws to assess brain-derived neurotropic factor, Insulin-like growth factor 1, insulin resistance, and C-reactive protein. Primary and secondary outcomes are changes in neuropsychological testing and cognitive concerns. Biomarkers will be examined to further understand the underlying relationship between physical activity and cognition.

Conclusion

The Memory & Motion study is designed to test whether increasing physical activity can improve cognitive functioning in breast cancer survivors. Results from this study could be used to guide development of interventions to improve cognitive functioning in breast cancer survivors.

Excess weight and physical inactivity are modifiable risk factors for breast cancer. Behavioral intervention is particularly important among women with an elevated risk profile. This trial tested an intervention that trained women to use a self-monitoring website to increase activity and lose weight. Women with BMI ≥27.5 kg/m(2) at elevated breast cancer risk were randomized to the intervention (N = 71) or usual care (N = 34). The intervention group received telephone-based coaching and used web-based self-monitoring tools. At 6 months, significant weight loss was observed in the intervention group (4.7 % loss from starting weight; SD = 4.7 %) relative to usual care (0.4 % gain; SD = 3.0 %) (p < 0.0001). By 12 months, the intervention group had lost 3.7 % of weight (SD = 5.4 %), compared to 1.3 % (SD = 4.2) for usual care (p = 0.003). At 12 months, accelerometer-measured moderate-to-vigorous physical activity increased by 12 min/day (SD = 24) compared to no change in usual care (p = 0.04. In summary, this web- and phone-based approach produced modest but significant improvements in weight and physical activity for women at elevated breast cancer risk.

Purpose

To explore contraceptive counseling and utilization among breast cancer survivors.

Methods

We enrolled reproductive-aged women with a history of breast cancer for a cross-sectional study. Participants were recruited via the Athena Breast Health Network and via the Young Survival Coalition's social media postings. Descriptive statistics were calculated to understand utilization of and feelings about contraceptive methods before, during, and after breast cancer treatment.

Results

Data presented here are from an online survey of 150 breast cancer survivors who completed the survey. Seventy-one percent (n = 105) of respondents reported being sexually active and not pregnant during their primary cancer treatment (surgery, chemotherapy, and/or radiation). Of these, 90% (n = 94) reported using any form of contraceptive, and the most common method was condoms (n = 55, 52%). Respondents reported that safety concerns had the biggest influence on their contraception method choice. Sixty-one percent (n = 92) reported receiving contraceptive counseling by their oncologist either before or after treatment; however, 49% (n = 45) of those did not receive a specific recommendation for a contraceptive method. Of respondents who reported receiving contraceptive counseling from their gynecologist, 44% (n = 35) reported that their gynecologist specifically recommended a copper intrauterine device (IUD). The majority of respondents (n = 76, 52%) wanted their oncologist to discuss contraceptive options with them and preferred to receive this counseling at the time of diagnosis (n = 81, 57%).

Conclusions

Breast cancer survivors in this study remained sexually active across the cancer care continuum and predominantly used condoms as their contraceptive method during treatment. Breast cancer patients would prefer contraceptive counseling from their oncologist at the time of their cancer diagnosis.

Implication for cancer survivors

Education efforts in the future should focus on initiatives to improve comprehensive contraceptive counseling at the time of diagnosis by an oncologist.

Objective

Breast cancer survivors experience problems with cognition that interfere with daily life and can last for years. In the general population, obesity and diabetes are risk factors for cognitive decline, and weight loss can improve cognition; however, the impact of intentional weight loss on cancer survivors' cognition has not been tested. We investigated the impact of weight loss and metformin on changes in cognitive function in a sample of breast cancer survivors.

Methods

Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomized to a weight loss intervention versus control and metformin versus placebo in a 2 × 2 factorial design. Outcomes were changes in five cognitive domains from baseline to 6 months measured by objective neurocognitive tests.

Results

There were no statistically significant intervention effects for the metformin or weight loss interventions in five neurocognitive domains. Baseline body mass index (BMI) was a significant effect modifier of the changes in verbal functioning for the weight loss (P = 0.009) and metformin interventions (P = 0.0125). These effect modifications were independent of percent weight loss achieved during the 6-month study period.

Conclusions

This randomized controlled trial of weight loss and metformin interventions that examined changes to cognition among breast cancer survivors suggests that these interventions may not improve cognitive functioning among breast cancer survivors in general. However, weight loss may improve verbal functioning among individuals with a higher BMI.

Background

Direct-to-consumer trackers and devices have potential to enhance theory-based physical activity interventions by offering a simple and pleasant way to help participants self-monitor their behavior. A secondary benefit of these devices is the opportunity for investigators to objectively track adherence to physical activity goals across weeks or even months, rather than relying on self-report or a small number of accelerometry wear periods. The use of consumer trackers for continuous monitoring of adherence has considerable potential to enhance physical activity research, but few studies have been published in this rapidly developing area.

Objective

The objective of the study was to assess the trajectory of physical activity adherence across a 16-week self-monitoring intervention, as measured by the Fitbit tracker.

Methods

Participants were 25 overweight or obese, postmenopausal women enrolled in the intervention arm of a randomized controlled physical activity intervention trial. Each participant received a 16-week technology-based intervention that used the Fitbit physical activity tracker and website. The overall study goal was 150 minutes/week of moderate to vigorous intensity physical activity (MVPA) and 10,000 steps/day; however, goals were set individually for each participant and updated at Week 4 based on progress. Adherence data were collected by the Fitbit and aggregated by Fitabase. Participants also wore an ActiGraph GT3X+ accelerometer for 7 days prior to the intervention and again during Week 16.

Results

The median participant logged 10 hours or more/day of Fitbit wear on 95% of the 112 intervention days, with no significant decline in wear over the study period. Participants averaged 7540 (SD 2373) steps/day and 82 minutes/week (SD 43) of accumulated "fairly active" and "very active" minutes during the intervention. At Week 4, 80% (20/25) of women chose to maintain/increase their individual MVPA goal and 72% (18/25) of participants chose to maintain/increase their step goal. Physical activity levels were relatively stable after peaking at 3 weeks, with only small declines of 8% for steps (P=.06) and 14% for MVPA (P=.05) by 16 weeks.

Conclusions

These data indicate that a sophisticated, direct-to-consumer activity tracker encouraged high levels of self-monitoring that were sustained over 16 weeks. Further study is needed to determine how to motivate additional gains in physical activity and evaluate the long-term utility of the Fitbit tracker as part of a strategy for chronic disease prevention.

Trial registration

Clinicaltrials.gov NCT01837147; http://clinicaltrials.gov/ct2/show/NCT01837147 (Archived by WebCite at http://www.webcitation.org/6d0VeQpvB).

INTRODUCTION: Cancer related cognitive decline is a common long-term side effect of cancer and its treatments among breast cancer survivors. Physical activity is a modifiable risk factor related to cognitive decline. However, existing research lacks consensus regarding the relationship between cognition and exercise as well as the impact of cancer treatments on this relationship. Baseline data from an ongoing randomized clinical trial was utilized to examine the relationship between self-reported and objectively measured cognition with physical activity. Exploratory analyses examined cancer treatments as potential moderators. METHODS: Breast cancer survivors (N = 253) completed a battery of neurocognitive tests, the PROMIS Cognitive abilities questionnaire, medical charts abstracted for treatment information, and wore an ActiGraph accelerometer at the waist for 7 days. Data were analyzed using multiple linear regression models. RESULTS: Participants were on average 58.5 (SD = 8.88) years old, diagnosed 3 years prior to enrollment (SD = 1.27) with 57% treated with chemotherapy and 80% receiving hormone therapy at baseline. Better self-reported cognitive ability was significantly associated with greater min of moderate to vigorous physical activity (MVPA; β = 0.070, se = 0.028, p = 0.012). There were no significant associations with any objectively measured cognitive domains. Time since diagnosis (years) was a significant moderator of MVPA and Processing Speed (β = -0.103, se = 0.043, p = 0.017). Treatment with chemotherapy and/or hormones did not significantly moderate the relationship between MVPA and any of the cognitive measures or domains. CONCLUSION: Findings suggest that physical activity is related to self-reported cognition but not objectively measured cognition. Greater physical activity was associated with faster processing speed in participants closer in time to their cancer diagnosis. These results emphasize the need for more research to understand when cancer survivors may benefit from physical activity and what aspects of cognition may be improved.

Background

The insulin-like growth factor-I (IGFI) receptor is a potential target for breast cancer treatment and may be influenced by dietary intake.

Methods

Nested, case-control study of 265 postmenopausal breast cancer survivors; primary breast cancer tissue was stained to determine IGFI receptor status. Change in carbohydrate intake from baseline to year 1 of study was estimated from 24-hour dietary recalls. Breast cancer recurrence cases (91) were matched to two controls (n = 174) on disease and study characteristics and counter matched on change in carbohydrate intake. Weighted conditional logistic regression models fit the risk of recurrence on IGFI receptor status and dietary change.

Results

Half of the tumors were IGFI receptor positive. Increased risk of recurrence was associated with IGFI receptor-positive status [HR 1.7; 95% confidence interval (CI), 1.2-2.5] and, separately, with a stable/increased intake of carbohydrates (HR 2.0; 95% CI, 1.3-5.0). There was a borderline significant interaction between those two variables (P = 0.11). Specifically, carbohydrate intake had no significant impact on risk of recurrence among women who were receptor negative, yet increased the risk of recurrence by more than 5-fold among women who were receptor positive (HR 5.5; 95% CI, 1.8-16.3).

Conclusions

Among women whose tumor tissue is positive for the IGFI receptor, reducing carbohydrate intake after diagnosis could reduce the risk of breast cancer recurrence. These findings need replication in a larger sample.

Impact

This is the first study to suggest that it may be possible to personalize dietary recommendations for breast cancer survivors based on molecular characteristics of their primary tumor tissue. .

Cyclin genes are key regulatory components of the cell cycle. With the development of new agents, cyclin-related genes are becoming increasingly important as they can be targeted. Yet, the biological implications of these alterations have not been fully studied. Clinical characteristics and outcome parameters were compared for patients harboring cyclin alterations versus not. CCN alterations were found in 13% of our population (50/392; all amplifications) and were associated with breast cancer (P < 0.0001), a higher median number of concomitant molecular alterations (P < 0.0001), and liver metastases (P = 0.046). Harboring a cyclin amplification was not associated with overall survival, the time to metastasis/recurrence, nor with the best progression-free survival. In a Cox regression model, gastrointestinal histology (P < 0.0001), PTEN (P < 0.0001), and CDK alterations (P = 0.041) had a significant association with poorer overall survival. CCN amplifications significantly correlated with alterations in FGF/FGFR family genes as well as in MET and ARFRP1. An extended correlation study shed light on a network of co-amplifications influenced in part by genes that were localized on the same amplicons. CCN amplifications are common across cancers and had distinctive biological associations. Customized combinations targeting the cyclin pathway as well as the extended co- amplification network may be necessary in order to address resistance mechanisms.

Purpose

Multiplex genomic tests are enabling oncologists to interrogate the DNA of their patients. However, few oncologists are proficient with respect to the implications of complex molecular diagnostics. We initiated a Molecular Tumor Board that focused on individual patients with advanced cancer whose tumors underwent genomic profiling, and here report our experience with breast cancer.

Methods

A multidisciplinary team that included physicians, scientists, geneticists, and bioinformatics/pathway specialists attended. All molecular tests were performed in a Clinical Laboratory Improvement Amendments environment (next-generation sequencing, 182 or 236 genes).

Results

Forty of 43 patients (93%; mean age, 59 years) had at least one theoretically actionable aberration (mean, 4.79 anomalies/patient). Median time from ordering to report was 27 days (median of approximately 11 days for specimen acquisition and approximately 14 days for diagnostic processing). Even if we considered distinct abnormalities in a gene as the same, there were only two patients with an identical molecular profile. Seventy-three genes (206 abnormalities; 119 distinct) were aberrant. Seventeen of the 43 patients (40%; median, seven previous therapies in the metastatic setting) were treated in a manner consistent with Molecular Tumor Board discussions; seven (16% of 43, or 41% of 17) achieved stable disease for 6 or more months (n = 2) or partial remission (n = 5). Lack of access to targeted medication was the most common reason that patients could not be treated.

Conclusion

Multidisciplinary molecular tumor boards may help to optimize the management of patients with advanced, heavily pretreated breast cancer who have undergone genomic testing. Facilitating availability of appropriately targeted drugs and clinical trials is needed.