Breast Cancer and weight gain

WEIGHT GAIN IS a common and distressing problem in women with newly diagnosed breast cancer. Since this phenomenon was first reported in 1978,¹research has led to a better understanding of those at greatest risk for weight gain (premenopausal women, those receiving chemotherapy), but the underlying basis for weight gain has remained poorly understood. Although widely believed to be due to overeating, available research provides little evidence that overeating plays a role in this weight gain, and at least one randomized trial has reported no benefit for dietary counseling.²

The study by Demark-Wahnefried et al³ that appears in this issue of the Journal of Clinical Oncology provides important insight into the problem of weight gain in premenopausal breast cancer patients receiving adjuvant chemotherapy. These researchers studied body composition and energy balance over the first year after breast cancer diagnosis in 53 women, 36 of whom received adjuvant chemotherapy. They reported that weight gain during adjuvant chemotherapy was associated with a simultaneous increase in fat mass and decrease in lean body mass, a pattern that is consistent with sarcopenic obesity. This form of obesity occurs in association with a number of medical conditions, including chronic corticosteroid use or prolonged physical inactivity, and in association with natural processes such as aging or menopause. All women who received chemotherapy in this study became menopausal, and it is certainly possible that menopause onset contributed in some indirect way to the development of sarcopenic obesity. However, a significantly lower level of physical activity throughout the year of observation was clearly demonstrated in the chemotherapy group. This lower level of physical activity resulted in reduced energy expenditure and was associated with lower lean body mass and weight gain. It seems to be a very plausible explanation for the weight gain seen in the chemotherapy group. Of equal importance is the fact that there was no evidence that either excess energy intake or a reduction in resting energy expenditure contributed to weight gain in women receiving chemotherapy. Thus the results of Demark-Wahnefried et al support the hypothesis that reduced physical activity is the primary factor responsible for weight gain during adjuvant chemotherapy for breast cancer. This reduced physical activity leads to an increase in fat mass and a reduction in lean body mass, consistent with sarcopenic obesity.

There were baseline imbalances between the two groups, with respect to weight, body mass index, lean body mass, and percent body fat. These differences are consistent with previous reports of an association of obesity with more advanced stage (involved axillary nodes) at breast cancer diagnosis,^4-6 and they reflect the fact that node-positive patients were more likely to receive chemotherapy. Adjustment for these baseline differences tended to reduce the statistical significance of the differences in body composition that were identified and highlight the need for confirmatory studies, however, the conclusions regarding physical activity remain valid.

Is it possible that the importance of overeating was underestimated in this study? Yes. The study involved only 53 women. Measurement of dietary intake is associated with a sizable measurement error regardless of the technique used. The methods used by the investigators (Food Frequency Questionnaire and 24-Hour Dietary Recall) did not involve prospective measurement of intake, with detailed ascertainment of portion sizes. This may have reduced the accuracy of their dietary measurements and increased measurement error. The 2.1-kg average weight gain over 1 year reported by Demark-Wahnefried et al³ reflects an energy imbalance of approximately 45 kcal/d (well within the range of measurement error of energy intake). It is possible that a small increase in energy intake was missed; however, the results reported here are consistent with earlier research, lending credibility to the authors’ conclusions. Nonetheless, future studies should measure dietary intake to further substantiate these observations.

The observations by Demark-Wahnefried et al³ regarding physical activity are consistent with an earlier report by our group⁷ that, in the context of a multidimensional intervention that included individual dietary counseling, individual physical activity recommendations and group psychosocial support, adoption of a regular physical activity program was the most important predictor of successful weight management in women with newly diagnosed breast cancer. The likelihood of successful weight management increased 1.7-fold for every 30 minutes of regular weekly physical activity, the most usual activity being brisk walking. Demark-Wahnefried et al’s results are also consistent with a report by Rock et al⁸ stating that routine physical activity predicted weight stability in breast cancer survivors.

How feasible is physical activity in this population of patients? Another recent report in the Journal of Clinical Oncology addresses this important question. Segal et al⁹randomized 123 recently diagnosed breast cancer patients to a control group, a self-directed physical activity group, or a supervised physical activity group. These 123 women comprised approximately one third of all those invited to participate, suggesting that many women receiving adjuvant chemotherapy for breast cancer are not interested in a physical activity program. However, this participation rate is similar to that for many randomized trials and may tell us more about breast cancer patients’ willingness to participate in randomized trials than their interest in physical activity. Segal et al reported an overall dropout rate of just under 20% in those who agreed to be randomized (which is low compared with exercise programs in the general population) and a compliance rate of more than 70% for those continuing in the intervention. No adverse outcomes of exercise were reported. An improvement in physical functioning was reported in those randomized to exercise, and this improvement was significant in the self-directed exercise group. Weight gain in all groups was less than might have been predicted. It tended to be lower in the exercise groups. This report provides strong evidence for the feasibility of exercise in women with newly diagnosed breast cancer, and it suggests that physical activity may minimize the problem of weight gain seen in this population. Others^10-12 have also demonstrated the safety and acceptability of physical activity in breast cancer patients, and have documented benefits that extend beyond weight control, such as reduced nausea and fatigue and enhanced quality of life.

Almost a quarter century after the original report of weight gain in women receiving adjuvant chemotherapy for breast cancer, it seems that we can finally appreciate one of the important underlying factors for this weight gain and begin to develop more effective strategies for its prevention. Should all women receiving adjuvant chemotherapy for breast cancer be advised to undertake a physical activity program? It would certainly be reasonable to advise these women that physical activity is safe, may prevent or minimize weight gain, and may be associated with enhanced physical functioning and quality of life. Additional research is needed to confirm the observations of Demark-Wahnefried et al,³ to identify optimal types and amounts of physical activity (for example, aerobic activity v resistance training), and to determine which approaches will be most effective in enhancing physical activity in these women. Women who are currently physically active or who are self-motivated to undertake physical activity should be supported in their attempts to be physically active. However, widespread recommendations for exercise in the absence of effective programs to promote physical activity are probably premature and may lead to frustration and reduced quality of life in other women.

There is a major unresolved question surrounding weight gain in women with newly diagnosed breast cancer. It continues to be unclear whether weight gain leads to an increased risk of recurrence and a worsened survival.^13-16 Obesity at diagnosis is associated with poorer outcomes in this group of patients.^17-20 What is not clear is whether an additional weight gain of 2% to 5% in those receiving adjuvant chemotherapy increases this effect. Demonstration of an adverse prognostic effect of weight gain would underscore the importance of research in this area and provide additional motivation for women with breast cancer, and their physicians, to develop and implement strategies to reduce weight gain. Resolution of this question should be a major research priority in early-stage breast cancer.