Obesity, Cancer Survivorship, and Race Relevance
In addition to the effects obesity may have on treatment efficacy and the challenges of providing treatment to obese compared with nonobese patients, it is also possible that obesity and associated chronic conditions alter the incidence, severity, or clinical course of common adverse effects of cancer treatment. Herein we review the available evidence regarding the potential influence of obesity on the burden of common adverse cancer treatment effects.
Lymphedema is a chronic condition characterized by an accumulation of protein-rich fluid and associated swelling of the affected body part. Cancer treatments such as lymph node dissection and radiotherapy can damage the lymphatic drainage routes, leading to fluid build-up, discomfort, and reduced mobility and function. Excess adiposity may increase risk of lymphedema by increased inflammation, added stress to the lymphatic system, or slower healing times after surgery. Although it may arise as a complication of treatment for several cancers, the majority of lymphedema research has been conducted within breast cancer.
There is convincing evidence that obesity increases risk of lymphedema after treatment for breast cancer. Prospective studies have reported statistically significantly higher lymphedema risk for obese vs normal-weight women, with odds ratios (OR) ranging from 2.93 to 3.60. Women who are overweight, but not obese, appear to be at lower but still statistically significantly increased risk, with odds ratios ranging from 2.00 to 2.24. The dose–response relationship between excess weight and lymphedema risk is further demonstrated by two separate studies, both reporting an odds ratio of 1.08 for each additional BMI unit above the normal weight category [95% CI = 1.05 to 1.12; 95% CI = 1.0004 to 1.165]. Similarly, a study conducted in Hong Kong observed statistically significantly higher BMI in breast cancer patients with lymphedema compared with matched control subjects; this is notable given that BMI was low in both groups (22.9±3.6kg/m for case subjects vs 21.8±3.1kg/m for control subjects). This suggests that adiposity is relevant to lymphedema across a wide range of body sizes, not just for those women who are clinically obese. Although it is unclear whether weight gain after treatment may increase the risk of lymphedema, weight loss has been shown to reduce lymphedema among overweight breast cancer survivors in a pilot study. Further research on the effects of weight loss on breast cancer survivors with lymphedema is ongoing within the Penn TREC Survivor Center.
Beyond breast cancer, the evidence is less consistent regarding the relevance of obesity as a risk factor for lymphedema. Three studies reported no association of BMI and incident lower extremity lymphedema among cervical cancer survivors. By contrast, a prospective cohort study among cervical cancer survivors found that low BMI (<18.5kg/m) was associated with increased frequency of lymphedema. However, these results may be affected by higher tobacco use and stage at diagnosis in this group. A retrospective chart review of 286 Japanese women with endometrial cancer observed no association of BMI and lymphedema, whereas a cross-sectional survey study among 243 Australian women observed a 2.7-fold increased risk for lymphedema among overweight compared with normal-weight endometrial cancer survivors (95% CI = 1.0 to 7.5). Beesley et al. also observed a non-statistically significant increase in lymphedema risk among overweight and obese ovarian cancer survivors compared with normal-weight women (OR = 1.9; 95% CI = 0.8 to 4.5).
Reduced quality of life, including functional impairment, psychosocial distress, limitations in social functioning, and emotional problems, is frequently reported by cancer survivors. Obesity has been associated with lower physical and functional well-being and poorer quality of life among endometrial cancer, breast cancer, prostate cancer, and colorectal cancer survivors. Two other studies with heterogeneous samples of cancer survivors (eg, breast, colorectal, prostate, bladder, uterine, and melanoma) have also demonstrated reduced quality of life among obese vs nonobese participants. Obesity is also associated with higher prevalence and severity of site-specific symptoms, such as incontinence in prostate cancer survivors.
Fatigue may be the most commonly reported and distressing symptom among cancer survivors. The overall prevalence of cancer-related fatigue (CRF) is estimated at 48% among cancer survivors, regardless of tumor type or treatment. Obesity has been positively associated with CRF for a number of cancer sites, including breast, endometrial, and childhood leukemia. Hypothesized pathways through which obesity might influence CRF include chronic inflammation, insulin resistance, and metabolic factors such as abnormalities of energy production and use. Factors predicting clinically significant CRF include a BMI greater than 25kg/m, weight gain, physical inactivity, and low physical functioning. Also, the severity of fatigue symptoms is associated with higher BMI. Additionally, researchers found that breast cancer survivors with CRF had higher BMIs and were more likely to be obese at baseline than survivors not experiencing CRF at 42 months after treatment.
Peripheral neuropathy is a potentially debilitating side effect of neurotoxic chemotherapy regimens and is a frequent reason for early cessation of treatment. Three classes of chemotherapy drugs commonly associated with peripheral neuropathy are taxanes, vinca alkaloids, and platinum compounds. Symptoms include numbness, tingling, burning/stabbing sensations, weakness of the hands or feet, and balance problems. Very little information is available regarding the potential relationship between obesity and peripheral neuropathy. In breast cancer, two studies observed no association between obesity and chemotherapy-induced peripheral neuropathy after taxane administration. Further, a study among multiple myeloma patients found that obesity did not increase the risk of peripheral neuropathy. However, given that obesity is also a strong risk factor for diabetes, which can induce neuropathy, it may be difficult to determine the independent effect of obesity on chemotherapy-induced neuropathy. One population-based cohort study observed that 9% of participants had comorbid diabetes at cancer diagnosis, with higher rates for some cancers (eg, 19% and 14% among pancreatic and uterine cancer patients, respectively).
The negative effect of cancer and its treatments on functional health among cancer patients, as compared with age-matched adults with no cancer history, has been observed in three large observational cohorts. The effect of obesity on functional health is also well demonstrated. No studies that specifically focused on the differential impact of cancer and its treatments on functional status among obese vs nonobese survivors were identified. However, given the evidence that both cancer and obesity are associated with worse functional health, it seems quite likely that functional health would be worse among obese than nonobese survivors.
Cancer treatments can increase survivors' risk for adverse cardiac effects, including hypertension, ischemia, left ventricular dysfunction, venous thromboembolism, and brachycardia. Because obesity is already a strong risk factor for cardiovascular disease and late effects of chemotherapy may not appear for many years after treatment completion, it is difficult to determine the specific role of obesity in treatment-related cardiac toxicities. Other sources of increased cardiovascular risk, such as weight gain after chemotherapy among breast cancer survivors, further complicate the question. The relationships between excess pretreatment weight, weight gain after treatment, and treatment-related cardiovascular outcomes have not been extensively studied.
Obesity and Adverse Treatment Effects
In addition to the effects obesity may have on treatment efficacy and the challenges of providing treatment to obese compared with nonobese patients, it is also possible that obesity and associated chronic conditions alter the incidence, severity, or clinical course of common adverse effects of cancer treatment. Herein we review the available evidence regarding the potential influence of obesity on the burden of common adverse cancer treatment effects.
Lymphedema
Lymphedema is a chronic condition characterized by an accumulation of protein-rich fluid and associated swelling of the affected body part. Cancer treatments such as lymph node dissection and radiotherapy can damage the lymphatic drainage routes, leading to fluid build-up, discomfort, and reduced mobility and function. Excess adiposity may increase risk of lymphedema by increased inflammation, added stress to the lymphatic system, or slower healing times after surgery. Although it may arise as a complication of treatment for several cancers, the majority of lymphedema research has been conducted within breast cancer.
There is convincing evidence that obesity increases risk of lymphedema after treatment for breast cancer. Prospective studies have reported statistically significantly higher lymphedema risk for obese vs normal-weight women, with odds ratios (OR) ranging from 2.93 to 3.60. Women who are overweight, but not obese, appear to be at lower but still statistically significantly increased risk, with odds ratios ranging from 2.00 to 2.24. The dose–response relationship between excess weight and lymphedema risk is further demonstrated by two separate studies, both reporting an odds ratio of 1.08 for each additional BMI unit above the normal weight category [95% CI = 1.05 to 1.12; 95% CI = 1.0004 to 1.165]. Similarly, a study conducted in Hong Kong observed statistically significantly higher BMI in breast cancer patients with lymphedema compared with matched control subjects; this is notable given that BMI was low in both groups (22.9±3.6kg/m for case subjects vs 21.8±3.1kg/m for control subjects). This suggests that adiposity is relevant to lymphedema across a wide range of body sizes, not just for those women who are clinically obese. Although it is unclear whether weight gain after treatment may increase the risk of lymphedema, weight loss has been shown to reduce lymphedema among overweight breast cancer survivors in a pilot study. Further research on the effects of weight loss on breast cancer survivors with lymphedema is ongoing within the Penn TREC Survivor Center.
Beyond breast cancer, the evidence is less consistent regarding the relevance of obesity as a risk factor for lymphedema. Three studies reported no association of BMI and incident lower extremity lymphedema among cervical cancer survivors. By contrast, a prospective cohort study among cervical cancer survivors found that low BMI (<18.5kg/m) was associated with increased frequency of lymphedema. However, these results may be affected by higher tobacco use and stage at diagnosis in this group. A retrospective chart review of 286 Japanese women with endometrial cancer observed no association of BMI and lymphedema, whereas a cross-sectional survey study among 243 Australian women observed a 2.7-fold increased risk for lymphedema among overweight compared with normal-weight endometrial cancer survivors (95% CI = 1.0 to 7.5). Beesley et al. also observed a non-statistically significant increase in lymphedema risk among overweight and obese ovarian cancer survivors compared with normal-weight women (OR = 1.9; 95% CI = 0.8 to 4.5).
Quality of Life
Reduced quality of life, including functional impairment, psychosocial distress, limitations in social functioning, and emotional problems, is frequently reported by cancer survivors. Obesity has been associated with lower physical and functional well-being and poorer quality of life among endometrial cancer, breast cancer, prostate cancer, and colorectal cancer survivors. Two other studies with heterogeneous samples of cancer survivors (eg, breast, colorectal, prostate, bladder, uterine, and melanoma) have also demonstrated reduced quality of life among obese vs nonobese participants. Obesity is also associated with higher prevalence and severity of site-specific symptoms, such as incontinence in prostate cancer survivors.
Fatigue
Fatigue may be the most commonly reported and distressing symptom among cancer survivors. The overall prevalence of cancer-related fatigue (CRF) is estimated at 48% among cancer survivors, regardless of tumor type or treatment. Obesity has been positively associated with CRF for a number of cancer sites, including breast, endometrial, and childhood leukemia. Hypothesized pathways through which obesity might influence CRF include chronic inflammation, insulin resistance, and metabolic factors such as abnormalities of energy production and use. Factors predicting clinically significant CRF include a BMI greater than 25kg/m, weight gain, physical inactivity, and low physical functioning. Also, the severity of fatigue symptoms is associated with higher BMI. Additionally, researchers found that breast cancer survivors with CRF had higher BMIs and were more likely to be obese at baseline than survivors not experiencing CRF at 42 months after treatment.
Peripheral Neuropathy
Peripheral neuropathy is a potentially debilitating side effect of neurotoxic chemotherapy regimens and is a frequent reason for early cessation of treatment. Three classes of chemotherapy drugs commonly associated with peripheral neuropathy are taxanes, vinca alkaloids, and platinum compounds. Symptoms include numbness, tingling, burning/stabbing sensations, weakness of the hands or feet, and balance problems. Very little information is available regarding the potential relationship between obesity and peripheral neuropathy. In breast cancer, two studies observed no association between obesity and chemotherapy-induced peripheral neuropathy after taxane administration. Further, a study among multiple myeloma patients found that obesity did not increase the risk of peripheral neuropathy. However, given that obesity is also a strong risk factor for diabetes, which can induce neuropathy, it may be difficult to determine the independent effect of obesity on chemotherapy-induced neuropathy. One population-based cohort study observed that 9% of participants had comorbid diabetes at cancer diagnosis, with higher rates for some cancers (eg, 19% and 14% among pancreatic and uterine cancer patients, respectively).
Functional Health
The negative effect of cancer and its treatments on functional health among cancer patients, as compared with age-matched adults with no cancer history, has been observed in three large observational cohorts. The effect of obesity on functional health is also well demonstrated. No studies that specifically focused on the differential impact of cancer and its treatments on functional status among obese vs nonobese survivors were identified. However, given the evidence that both cancer and obesity are associated with worse functional health, it seems quite likely that functional health would be worse among obese than nonobese survivors.
Cardiotoxicity
Cancer treatments can increase survivors' risk for adverse cardiac effects, including hypertension, ischemia, left ventricular dysfunction, venous thromboembolism, and brachycardia. Because obesity is already a strong risk factor for cardiovascular disease and late effects of chemotherapy may not appear for many years after treatment completion, it is difficult to determine the specific role of obesity in treatment-related cardiac toxicities. Other sources of increased cardiovascular risk, such as weight gain after chemotherapy among breast cancer survivors, further complicate the question. The relationships between excess pretreatment weight, weight gain after treatment, and treatment-related cardiovascular outcomes have not been extensively studied.