Weight and weight change following breast cancer: evidence from a prospective, population-based, breast cancer cohort study

Maintaining a healthy body weight and avoiding excessive weight gain throughout life are common public health messages with respect to breast cancer prevention and recovery [1,2]. Overweight or obesity following breast cancer is associated with greater morbidity [3] and mortality [4,5]. Specifically, overweight or obesity are associated with higher rates of treatment-related sequelae, such as lymphedema, fatigue and arthralgia [6-14], and have been associated with increased risk (up to four-fold) of developing other chronic diseases, such as type II diabetes and cardiovascular disease [15,16]. Findings from a meta-analysis also demonstrated that risk of breast cancer-specific and all-cause mortality was 1.3 times higher (HR = 1.3, 95% CI: 1.2- 1.5; and 1.3: 1.2-1.5, respectively) in obese women compared with non-obese women [17]. Weight loss, in particular for those who enter their cancer diagnosis malnourished and underweight, has also been linked with poor outcomes [1,18]. However, to date, weight gain rather than weight change, with consideration to gains as well as losses, has been the focus of research attention for women with breast cancer.

Following a breast cancer diagnosis, weight gains exceeding five kilograms have been observed over periods between six months [19-22] and sixty months [23] post-surgery and have been observed in retrospective [24-26], as well as prospective [19-23,27-35] studies. Cohorts studied have included both pre- and post-menopausal women [33,36], and those followed during and following chemotherapy [19,20,22,27,28,31,34,37], radiotherapy [22,28] and endocrine therapy [30]. While chemotherapy has long been associated with weight gain, changes in chemotherapy regimens (including type and duration of administration) make its current contribution to weight gain unclear. Other factors that have been associated with weight gain post-breast cancer, though inconsistently, include younger age, pre-menopausal status and/or having a lower body mass index (BMI) at time of diagnosis [38].

While earlier studies, particularly those that assessed the effects of chemotherapy compared changes in weight and body composition against patients who just received localised treatment [22,28], the question of whether these observed changes can be attributed to aging or to breast cancer and its treatment remain. Understanding the contribution of the disease itself to weight change is important for determining the optimal setting (patient or public health/community), timing, type and need for breast cancer specific advice (e.g., taking into account treatment-related sequelae) for weight control. The purpose of this work is to describe changes in body weight in a population-based sample of women diagnosed with breast cancer, assessed prospectively between six and 72 months post-surgery, to compare weight with age-matched normative data, and to explore the personal, diagnostic, treatment and behavioral characteristics associated with body weight following breast cancer.

Ethical approval was obtained from a university human research ethics committee (Queensland University of Technology, Reference Number 2179H) and access to patients followed the standard procedures of the local cancer registry. All women provided written, informed consent.

This is the first, population-based, study of its size to assess weight and change in body weight over a six-year period following breast cancer and to compare weight changes with age-matched normative data. At six-months post-surgery, more than half of women (57%) were overweight or obese, and by six-years post-breast cancer 68% of women were overweight or obese; this compares to fewer than 50% of age-matched controls [44]. While median weight gain for all study participants over the six-year follow-up period was less than one kilogram, measures of central tendency can be misleading since these data also include weight losses that may result from the cachexia of advanced disease. Thus, studying individual trajectories is important.

In this cohort, the two women reporting the most extreme weight losses (23 and 24 kg) had early stage disease and good prognosis, suggesting that extreme weight loss was unlikely to be associated with cachexia of advanced disease. Nonetheless, for the 15% to 24% of the sample who lost weight, it is unclear from our data whether this loss was intentional, or not, and if intentional whether it resulted from weight loss strategies that are aligned with current guidelines aimed at durable change (i.e., weight loss resulting from energy restricted diets that promote a loss of weight of between 0.5 and 1 kg per week, combined with increased physical activity and behavior modification) [45]. Moreover, because data on body composition were not collected, changes in absolute levels of adiposity within the weight loss group are unknown. This is important to highlight, since sarcopenic changes are prevalent in this population, especially among those who receive chemotherapy [22,24], and as such, it is unclear from our data whether weight losses were likely advantageous or detrimental to overall long-term health.

Over half of the PTS participants gained weight in the short (6 to 18 months) and longer-term (6 to 72 months) post-surgery. Of these women, 80% gained more weight than the average weight gain experienced by age-matched counterparts. Further, by 18- and 72-months post-breast cancer diagnosis, 24% and 39% of women, respectively, gained a magnitude of weight (that is, weight gain that led to more than one unit increase in BMI [43]) that is linked with adverse health [43], risk of chronic disease [1,16] and poorer survival [17,46].

Understanding characteristics associated with weight at diagnosis and weight change post-surgery may provide insight into the potential for identifying subgroups of women who would benefit most from a ‘healthy weight’ program. Our results suggest that women treated on the non-dominant side, those with more extensive axillary lymph node dissection, those receiving radiation treatment and those not engaging in sufficient levels of physical activity each week tended to be heavier post-surgery. With the exception of physical activity, these characteristics are non-modifiable, are modest confounders of the association between physical activity and weight, and warrant further exploration as potential effect modifiers in future research. Nonetheless, since overweight, obesity and weight gain post-breast cancer are common and persistent contemporary breast cancer survivorship issues that challenge quality and quantity of life, the integration of healthy weight management into standard breast cancer care for all women appears necessary.

Our findings demonstrating that those meeting national physical activity guidelines (i.e., at least 150 minutes of moderate activity/week) have clinically lower body weights than those insufficiently active or sedentary are not surprising. Evidence-based clinical recommendations for achieving healthy weight and/or weight loss for the general population (and also for cancer survivors) includes a multicomponent approach, involving physical activity, as well as diet and behavior modification [18]. It is acknowledged however that more information within this specific patient population is required to determine optimal timing of intervention, sequencing of behavioral components, as well as the need to evaluate impact of weight maintenance on breast cancer-specific and overall health outcomes. Nonetheless, findings from this study clearly highlight the need for intervention.

Potential limitations of this work are that the PTS sample was diagnosed over 10 years ago (2002) and loss to follow-up in this cohort was greater than 20%, which threatens the generalizability of findings [47,48]. Nonetheless, our data contribute the most recent prospectively and clinically-measured body weight data within the literature and our study represents one of the few that have compared weight change among breast cancer survivors to population-based controls. Published literature suggests that during chemotherapy (first 6/12 months) weight does fluctuate [19,24,29]. Clinical weight was not collected pre-treatment, however based on self-reported weight pre-diagnosis, body weight did not change significantly during the treatment period. Future studies should build in data collection periods that might address this issue. Further, although not perfectly matched, the follow-up period between the PTS sample (2002–2008) and the AusDiab normative sample (1999/2000-2004/2005) are similar, which in turn enabled informative weight comparisons with age-matched data. Importantly, the PTS sample has characteristics representative of the wider breast cancer population and study design involved a long follow-up period (six years post-surgery) enabling short and longer-term weight change to be evaluated. Further, previous work has reported weight changes for the group as a whole [19,23,30,32,34]; our results show that group means mask key findings.

In summary, weight at six months post-diagnosis of breast cancer and weight change post-surgery remains a contemporary public health issue. There is a real need for the incorporation of weight management strategies into breast cancer care for all women diagnosed, though it may be even more important for women in certain subgroups (e.g., those participating in insufficient levels of physical activity). In doing so, the potential for prevention and/or attenuation of breast cancer treatment-sequelae, subsequent chronic disease and improvements in quality and quantity of life following breast cancer is significant.