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Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502
* To whom correspondence should be addressed. E-mail: rchlebow{at}whi.org.
Interest in the potential influence of lifestyle factors on breast cancer recurrence and survival after breast cancer diagnosis was originally based on observational studies comparing patient survival in countries with high fat consumption such as the United States and the United Kingdom to those with low consumption (such as Japan) (1,2). Based on such evidence, a prospective clinical trial to evaluate the effect of dietary fat intake reduction on breast cancer recurrence was initiated in the early 1980s but not completed (3,4) because interest waned with the emergent success of systemic hormonal therapy and chemotherapy as reported by the Early Breast Cancer Trialists' Collaborative Group (5).
Although the original focus on dietary fat intake reduction as potential mediator of the breast cancer effects provided the rationale for subsequent full-scale clinical trials, which are now nearing completion, preclinical and observational studies have subsequently expanded the range of lifestyle factors with potential influence on breast cancer outcome to include obesity and its correlates of higher caloric intake and lower physical activity as well as the potential role for specific nutrients including vegetables and fruits in this process.
The task of evaluating the influence of individual dietary and other lifestyle factors on breast cancer outcomes in observational studies is limited by the difficulty in accurately measuring exposures given available methodology (6–8), the limited range of exposures seen in a general population, and the common commingling of exposures of interest (8). For example, women who are obese are more likely to have higher caloric intake, higher dietary fat intakes, and be less physically active compared with leaner women. In the sections below, current evidence regarding the role of individual and collective lifestyle factors on breast cancer recurrence risk are reviewed as well as the status of prospective clinical trials in this area.
Dietary intake and breast cancer outcome
A total of 14 articles have examined relationships between breast cancer recurrence and/or survival and dietary intakes in women with diagnosed breast cancer (9,10). As mentioned previously, it is often difficult to separate out individual dietary components. With respect to dietary fat intake, 7 of the 14 reports addressing this issue describe a significant association with breast cancer outcomes. Gregorio et al. (11) described a relative risk (RR) of 1.44 for each 1000 g/mo fat intake for distant disease recurrence (P < 0.01). Nomuar et al. (12) found increased deaths with increased fat intake in white women (RR 3.17, CI 1.17–8.55), and Rohan et al. had similar findings in their overall cohort of 412 patients (13), as did Zhang (14) in a 698 patient cohort. In a 240 breast cancer patient population, a significantly increased risk of treatment failure with increasing fat intake was seen (15). Jain et al. (16) reported increased risk of death with higher energy-adjusted total fat intake in their cohort. Finally, in a 472 patient cohort, breast cancer recurrence risk was significantly associated with age-adjusted butter, margarine, and lard intakes (17). In contrast, no such associations were seen in the other 7 cohort reports (18–24).
The reports relating vegetable intake or related nutrients to breast cancer outcomes also provide a mixed picture and have recently been reviewed (10). Eight studies have examined this question, and 3 found a significant association of increased intakes with decreased risk of death in breast cancer cohorts (16,13,21).
The suggestion of associations with dietary fat and vegetable intake with breast cancer outcome supported the initiation of 2 phase III studies evaluating dietary intake influence on breast cancer recurrence risk.
The Women's Health Eating and Living (WHEL) study has entered 3109 pre- and postmenopausal breast cancer patients to a control condition on a dietary intervention emphasizing vegetable and fruit intake, including 16 ounces of vegetable juice, a target of 15% to 20% energy from fat, and 30 g of dietary fiber daily (25). Importantly, this dietary approach has not been associated with weight loss (26). Follow-up continues with results regarding breast cancer outcomes anticipated in 
1 y.
The Women's Intervention Nutrition Study (WINS) initially demonstrated feasibility of a lifestyle intervention in a multicenter trial setting (27). The WINS outcome study has randomized 2437 women within 1 y of a breast cancer diagnosis to a control group or a dietary intervention group with all receiving standard breast cancer management. The low-fat eating plan intervention targeted fat intake reduction, and interim efficacy results have been presented at the American Society of Clinical Oncology 2005 meeting. After a median of 60 mo, dietary fat intake was significantly lower in the intervention group (P < 0.001), corresponding with a significantly lower (P = 0.005) mean body weight in intervention participants. The hazard ratio in the intervention group compared with control was 0.76 (95% CI 0.60–0.98, P = 0.034 for adjusted Cox model analysis) (28), suggesting benefit for the dietary change. Follow-up of participants continues to meet original protocol design assumptions.
Obesity and breast cancer outcome
More recently, attention has been directed at a potential role of other lifestyle factors on breast cancer patient outcome. Overweight and obese breast cancer patients have poorer survival and increased recurrence risk compared with lighter weight patients. In a recent review of 34 published studies, statistically significant association between obesity and worse prognosis was seen in 25, a nonsignificant effect was seen in 4, and no effect was seen in 2 reports (29). In a recent report from the large Nurses' Health Study cohort, weight and weight gain were significantly associated with recurrence and mortality, but only in nonsmokers (24). However, the results are mixed, with a recent report finding that obesity was not related to recurrence risk in breast cancer patients receiving tamoxifen (30).
Physical activity and breast cancer outcome
Several studies have evaluated the association between a breast cancer diagnosis and decreased physical activity (31), and relations among higher BMI, lower physical activity, and high estrogen levels have been described (32). Against this background, investigators from the Nurses' Health Study examined the relation between physical activity after a breast cancer diagnosis and breast cancer mortality (33). In this setting, higher physical activity was associated with lower risk of death from the disease. The equivalent of walking 3–5 h/wk resulted in the greatest apparent benefit.
These findings have been recently extended by Abrahamson et al. (34), who examined the effects of physical activity 1 y before a cancer diagnosis. They found a modest reduction in risk of death for women with diagnosed breast cancer with the higherst quartile of activity compared with those with the lowest quartile of activity [Hazard Ratio (HR) 0.78 95%, confidence interval (CI) 0.56 to 1.08], especially in women overweight or obese (HR 0.70, 95% CI 0.49 to 0.99). Such accumulated data suggest a relation between physical activity and cancer survival (35).
Taken together, the available observational studies and the interim analysis of a randomized prospective clinical adjuvant breast cancer trial (28) suggest that future studies should examine the addition of increased physical activity and caloric intake reduction (to target weight loss) to a lifestyle intervention targeting fat intake reduction to potentially enhance an anticancer effect. In addition, efforts should be made to facilitate the widescale adoption of such an intervention, if successful, by reducing the breast cancer patient participant burden and overall cost. Such a clinical trial is in the planning stages and should help address remaining questions in this area. For now, we are left with a preliminary signal that lifestyle change may influence breast cancer patient outcome. Pending more definitive evidence, such intervention may soon find a place in standard breast cancer patient management.
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FOOTNOTES |
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2 Author Disclosure: No relationships to disclose.
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LITERATURE CITED |
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