Breast Cancer, Body Weight, Adiposity, and Survival
By Wendy Demark-Wahnefried, PhD, RD, and Cheryl L. Rock, PhD, RD
Relationships between survival among breast cancer patients and body weight, relative adiposity, or other indicators of obesity have been explored in observational studies. A critical review and analysis of 13 cohort studies and one case-control study on the association between obesity at diagnosis and poor prognosis, published in 1990, concluded that increased body weight exerts "a negative, yet modest, prognostic effect" most relative risk estimates ranged from 1.12 to 4.17, with most clustering in the 1.5-2.0 range (confidence intervals were not given).1
Since that time, 25 published studies have examined associations either between premorbid weight status or weight status at the time of diagnosis (estimated by relative weight for height or body mass index [BMI]) and breast cancer recurrence and/or survival. In 16 of the 25 studies, increased BMI and/or body weight increased the risk of recurrent disease and/or decreased survival;2-17 seven studies produced null findings;18-24 and two studies showed an inverse association between weight status and local recurrence25 or mortality.26 In those studies that found a significant association, obese women with breast cancer had a 30-540% increased risk of overall mortality during the time period examined, compared to similarly staged breast cancer patients.
Thus, a majority of studies suggest that obesity is a risk factor for progressive disease. This relationship appears to be more pronounced among women who are diagnosed with early-stage disease5,17 and among those who have estrogen receptor-positive tumors.3 Although BMI was not found to be a risk factor for increased breast cancer mortality in one study,26 android body fat distribution (higher suprailiac:thigh ratio) was found to be a significant prognostic indicator, with a hazard ratio of 2.6 (95% confidence interval [CI] 1.63, 4.17). In most of these studies, the effect of obesity on prognosis was examined using premorbid weight or weight at diagnosis. It is not yet known whether post-diagnosis weight reduction through diet and/or increased physical activity might alter this relationship.
Weight Gain After Diagnosis
After a breast cancer diagnosis, women often gain weight (commonly from 2.5-6.2 kg; however, greater gains are not unusual). Weight gain usually is more pronounced among patients who receive adjuvant chemotherapy and among those who were premenopausal at diagnosis.27 Other factors associated with post-diagnosis weight gain are African-American ethnicity and current energy intake. Higher prediagnosis BMI, older age at diagnosis, higher level of education, and higher exercise level have been found to be associated with less weight gain.28 Evidence on whether weight gain after diagnosis affects prognosis is mixed. Camoriano et al followed 646 patients with breast cancer for a median of 6.6 years and found that premenopausal women who gained more than the median amount of weight (5.9 kg) were 1.5 times more likely to relapse and 1.6 times more likely to die of their breast cancer.9 Results of a study by Chlebowski et al are similar to these findings.29 In contrast, two other studies failed to identify any association between post-diagnosis weight gain and prognosis.30,31 Several reports found that breast cancer survivors find weight gain distressing and that it may negatively impact quality of life.27 In a cross-sectional study conducted among 56 breast cancer patients, as well as 52 healthy women, BMI was directly associated with greater depressive symptomology and abnormal eating attitudes and behavior in both groups.32
The nature of the weight gain among women with breast cancer (at least those who receive adjuvant chemotherapy) is unique. In most adults, weight gain is characterized by gains in both lean and adipose tissue. However, clinical studies on women with breast cancer that have measured body composition change (via computerized tomography, dual energy X-ray absorptiometry, or in vivo neutron capture) consistently have found either no gains in lean tissue mass or actual losses in lean tissue mass as weight and adipose tissue increase.33-37
A few small studies, as well as early data from large diet intervention trials, have examined the effect of dietary guidance and/or increased physical activity on post-diagnosis weight gain. In one report, routine prospective diet counseling aimed at weight maintenance produced small, insignificant reductions in energy intake and weight gain among women receiving adjuvant chemotherapy for resected breast cancer.38 In 290 women enrolled in the feasibility trial of the Women’s Intervention Nutrition Study (WINS), which tested a low-fat diet intervention on risk of recurrence, reducing fat intake from 33% to 21% of total energy intake was associated with an average weight loss of 1.5 kg over 18 months in the intervention group, compared with an average gain of 1.8 kg in the control group (P < 0.01).39 Although percent energy from fat was significantly lower in the intervention group than the control group (P < 0.01), significant changes in reported energy intake were not observed in either group. In the Women’s Healthy Eating and Living (WHEL) study, which tested a high-vegetable, low-fat diet on risk of recurrence, reduced intake of fat did not significantly affect weight loss (although weight loss was not a goal of that study).40 Two small intervention studies incorporating both dietary guidance and increased physical activity produced significant reductions in body weight in overweight women (or weight maintenance in those not overweight).41,42 Aerobic exercise was identified as the strongest predictor of success when the intervention components were analyzed for independent effects.41 Other studies testing various approaches to promoting weight loss or weight maintenance in women with breast cancer are in progress.
Mechanisms
Several mechanisms have been proposed to explain the adverse effect of excess adiposity on progression of breast cancer. Adipose tissue serves as an important extragonadal source of estrogens from precursor adrenal androgens, and increased adipose tissue affects levels of circulating gonadal hormones.43 Obesity consistently has been associated with increased serum concentrations of estrone and estradiol, and decreased levels of sex hormone-binding globulin.44,45 In animals, estrogens promote breast tumorigenesis.46 Another possible mechanism relates to the interactions of insulin and insulin-like growth factor 1 (IGF1) with adiposity and weight gain.47,48 A recent study in 512 non-diabetic women with early breast cancer found that high fasting insulin levels were positively associated with distant recurrence and death; the hazard ratio for distant recurrence for those in the highest (> 51.9 pmol/L) vs. the lowest (< 27.0 pmol/L) insulin quartile was 2.9 (95% CI, 1.2-3.3) and the hazard ratio for death was 3.1 (95% CI, 1.7-5.7).49 Increased BMI also correlated with insulin levels. In cell culture, insulin and IGF1 exhibit mitogenic effects that influence both premalignant and cancerous stages of cell growth.47
Conclusion
The majority of studies have found that increased BMI and/or body weight at the time of breast cancer diagnosis is associated with increased risk of recurrence and death (from multiple causes). Studies are mixed on whether post-diagnosis weight gain affects the risk of recurrence and death. General cancer prevention guidelines currently form the basis of current dietary recommendations for breast cancer survivors. For this population, encouraging healthy weight control by emphasizing exercise to preserve or increase lean body mass may be particularly helpful.
Dr. Demark-Wahnefried is Associate Professor, Department of Surgery, Duke Comprehensive Cancer Center, Cancer Prevention, Detection, and Control Program, Durham, NC; Dr. Rock is Associate Professor, University of California, San Diego, Department of Family and Preventive Medicine, Cancer Prevention and Control Program.
The research included in both of these articles was supported by NCI grants CA69375 (CR), and CA62215, CA92468, and CA81191 (WD). This research also was made possible in part by funds received from the Cancer Research Fund (CRP grant 99-00548V-10147), under Interagency Agreement #97-12013 (University of California, Davis, contract #98-00924V) with the Department of Health Services Cancer Research Section. The views expressed herein represent those of the authors and do not necessarily represent the position of the State of California, Department of Health Services.
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Demark-Wahnefried W, Rock CL. Breast cancer, body weight, adiposity, and survival. Altern Ther Women's Health 2002;4:12-16.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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