DISCUSSION
ovarian cancer, cancer
OVARIAN CANCER, RECURRENCE, RECURRENT OVARIAN CANCER, BREAST CANCER, CANCER, DISEASE, RECRUITMENT, TUMORIGENESIS
Our exercise intervention among women with ovarian cancer resulted in changes in two prespecified biomarkers in the exercise group compared to the attention‐control group, a 57.4% reduction in serum leptin and a 14.9% reduction in IGF‐1. No exercise intervention effect was seen for CA‐125, CRP, or insulin. An exercise intervention effect was observed for VEGF with a 20.0% increase in the exercise compared to the attention‐control group, but no effect of exercise was seen for the other exploratory biomarkers, adiponectin, IL‐6, or TNFα. To our knowledge, this is the first intervention study reporting the effects of exercise on cancer‐related circulating biomarkers in women with ovarian cancer.Similar to our findings, a recent randomized controlled trial in women with breast cancer, showed a favorable exercise effect on serum IGF‐1.The relationship of post diagnostic serum IGF‐1 levels and cancer survival has not been well studied. It is thought that IGF‐1 increases cellular growth and may, therefore, promote tumorigenesis.Leptin levels are strongly influenced by both physical activityEvidence suggests that leptin may be involved in the metastatic processVEGF plays a key role in angiogenesis,Over the course of our 6‐month study, circulating VEGF concentrations increased significantly in those assigned to the exercise intervention group compared to those in the attention‐control group. Our result is in contrast to two independent randomized controlled trials in inactive but health postmenopausal women. In a 12‐month RCT, Brenner et al., reported that there was no difference in circulating VEGF between study arms in which women were randomized to 150 (Unlike a meta‐analysis of women with breast cancer,To the best of our knowledge, no randomized trials have been reported examining the effect of exercise on overall survival in women with ovarian cancer. In our exploratory analysis, we found no benefit on overall survival of our 6‐month exercise intervention. This contrasts with several observational studies that have reported exercise post diagnosis associated with reduced mortality of ovarian cancer.As changes in cancer‐related biomarkers occurred as a result of the 6‐month exercise intervention, future research may be warranted to investigate the effect of exercise on mortality in women soon after diagnosis, as our study population was enrolled after completing initial treatment, on an average of 1.7 years post‐diagnosis, or investigate an exercise intervention of longer duration.Study strengths included a 6‐month study duration, randomized design, and the population‐based recruitment approach. The external validity of our findings was strengthened by the limited study exclusion criteria which resulted in recruitment of a broad sample of ovarian cancer survivors. However, it should be noted that the generalizability of our results may be affected by the limited racial diversity in our study population. Additionally, the home‐based, telephone‐delivered exercise program allows for straightforward implementation into a clinic‐ or community‐based setting and is cost‐effective. Lastly, adherence to the exercise intervention was excellent.Our study is not without limitations. First, our study involved the use of self‐reported physical activity; however, the prospective study design, daily exercise recording, and weekly phone calls with the exercise trainer minimized potential recall bias. In addition, the population had variability in disease stage and clinical characteristics at enrollment with a substantial number of women experiencing recurrent ovarian cancer during the 6‐month study and the effect of this disease burden on the biomarkers assessed is unclear. Notably, the effect of exercise on leptin was only evident in those women who had a recurrence during the study, suggesting a differing effect of exercise on those who had a recurrence versus women who remained disease free. However, this finding should be interpreted with caution as the recurrence status of some women could not be determined. As a subset of participants were included in the biomarker analysis and survival was an exploratory outcome all results are exploratory and thus should be interpreted cautiously.In summary, we found that a 6‐month home‐based exercise intervention in women with ovarian cancer resulted in a reduction in leptin and IGF‐1 levels which may have a beneficial effect on cancer‐related outcomes, but also an increase in circulating levels of VEGF. We did not observe any effect of the exercise intervention on survival. Future studies examining the impact of modifiable lifestyle behaviors on ovarian cancer outcomes are needed. The LIVES study is examining the impact of a diet and exercise intervention on ovarian cancer survival.