On average, breast cancer patients in our study gained 1.7 kg of weight and 2.1% body fat over 2 years. More than 68% and 74% of the women experienced gains in weight and percent body fat, respectively. The mean increases for those who gained weight and percent body fat were 3.9 kg and 3.6%, with a range of 0.1 kg to 27.0 kg and 0.1% to 15.0%. The weight gain that we observed is comparable to that reported by others in women with recently diagnosed breast cancer. Goodwin et al (4
) reported that 84% of 535 breast cancer patients gained weight in the first year after diagnosis, with a mean weight gain of 1.6 kg overall. In a study by Rock et al (1
), 60% of 1116 women enrolled in the WHEL Study reported weight gain from one year before diagnosis to within four years after diagnosis. The mean weight gain was 2.7 kg.
The weight gain we and others have observed in breast cancer survivors is larger than that observed by others in healthy women. Williamson et al (32
) studied weight gain over a 10-year period in the 1970’s in 6,135 women who participated in the NHANES I Study. Over 10 years, women aged 45 to 55 years gained only 0.79 kg (0.08 kg/yr), whereas those aged 55 years and older lost weight. Our findings cannot be compared directly with the NHANES I study, however, women with breast cancer may experience a greater weight gain than women in the general population.
The effects of weight gain on breast cancer recurrence have been debated in the literature. Some (7
), but not all (33
) investigators have associated weight gain with an earlier disease recurrence. Camoriano et al (8
) followed 646 breast cancer patients for a median of 6.6 years and found that premenopausal women who gained more than 5.9 kg were 1.5 times more likely to relapse and 1.6 times more likely to die of their breast cancer than were women gaining less weight.
Although it remains to be determined whether post-diagnosis weight gain influences risk for progressive disease, it is known that weight gain adversely affects risk for cardiovascular disease, hypertension, and diabetes (15
). Furthermore, many studies have identified obesity as an important negative prognostic factor for breast cancer survival (10
). In a review by Chlebowski et al (10
), 17 of 26 studies found increased weight to be a significant risk factor for recurrent disease and decreased survival; seven studies produced null findings; and two studies found an inverse association between weight and recurrence. In the studies that found a significant positive association between overweight and progressive disease, women categorized in the higher vs. lower levels of obesity exhibited a 30% to 540% increased risk of death. Data from the National Surgical Adjuvant Breast and Bowel Project in 3,385 women indicated that while obesity did not increase risk for breast cancer recurrence or death, obesity did increase risk of overall death, risk of other cancers, and death from cardiac disease (38
). It is currently unknown whether post-diagnosis weight reduction modifies the relationship between obesity and breast cancer recurrence and mortality.
Several mechanisms have been proposed to explain the adverse effect of adiposity and weight gain on breast cancer prognosis. One mechanism rests on greater peripheral conversion of androstenedione to estradiol and inhibition of synthesis of sex hormone binding globulin with an increase in free estradiol which stimulates neoplastic cells (39
), especially in postmenopausal women (23
). We have previously reported an association between increased adiposity and increased concentrations of estrone, estradiol, and free estradiol in the HEAL cohort of breast cancer survivors (23
). Another mechanism relates to insulin and IGF-1 and the interactions of these hormones with adiposity (40
). Insulin and IGFs exhibit mitogenic effects that influence both premalignant and cancerous stages of cell growth. Both insulin and IGF-1 stimulate the synthesis of sex steroids, and thus, their cancer-promoting effects in the progression of breast cancer may be mediated by an effect on sex hormones. Another explanation for poorer survival may be associated with obese women failing to respond to treatment as a result of the common practice of chemotherapy capping at a body surface area of 2 m2
, which may offer suboptimal treatment benefit (41
In our study, higher disease stage, being postmenopausal, and less participation in physical activity were significantly related to gains in body weight. Receiving chemotherapy was also associated with greater weight gain, however this observation was limited to postmenopausal women and women who did not increase their physical activity from baseline to within 3 years after diagnosis. Goodwin et al. (4
) examined factors associated with weight gain during the subsequent year after diagnosis in 535 newly diagnosed breast cancer survivors. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain.
A study by Demark-Wahnefried studied energy balance over the first year after breast cancer diagnosis in 53 premenopausal women (2
). Weight gain during chemotherapy was associated with an increase in fat mass and decrease in lean body mass, a pattern consistent with sarcopenic obesity. This form of obesity is associated with reduced physical activity, aging, and menopause. A significantly lower level of physical activity throughout the year of observation was demonstrated. The authors conclude that reduced physical activity is the primary factor responsible for weight gain during chemotherapy for breast cancer. Demark-Wahnefried et al’s results are also consistent with a report by Rock et al (1
) stating that physical activity predicted weight stability in 1116 breast cancer survivors participating in the WHEL Study.
Despite strong evidence suggesting that regular physical activity can protect against gains in body fat and weight, only 32% of breast cancer survivors enrolled in the HEAL Study engaged in the recommended level of physical activity defined as 150 min per week of moderate- to vigorous-intensity physical activity (24
). This percentage is similar to the proportion of healthy U.S. women (27%) meeting the current recommendation (29
). Recently, we reported that women diagnosed with breast cancer were significantly less physically active within their first year after diagnosis than they were one year before diagnosis (22
). While physical activity levels reported three years after diagnosis increased to pre-diagnosis levels for approximately 50% of the sample, this was mostly limited to non-obese women (24
). Exercise interventions and physical activity programs focused on increasing physical activity among breast cancer survivors with the ultimate goal of testing the effects on prognosis are needed. Previous research has also shown beneficial effects of dietary interventions on breast cancer prognosis in breast cancer survivors (42
). Studies examining the combination of diet and physical activity on prognosis are also needed.
The HEAL Study has several strengths. It is one of a handful that has examined changes in measured body weight for a relatively long follow-up period, and the largest study reporting changes in body fat measured via DEXA. However, a limitation of our study is that we were unable to measure weight and percent body fat at other time points (e.g., within the second year after diagnosis). Women may have initially gained and then lost weight during this time. Thus, we are unable to report the maximal gains in body weight and body fat within three years after a breast cancer diagnosis. Another limitation of the study is that some women were recruited into the study while undergoing treatment, while others had not begun treatment or had completed treatment. Some women may have already experienced changes in weight or body fat after diagnosis, but prior to enrollment in the study. Lastly, our sample was highly educated and mostly non-Hispanic White, therefore, we cannot be sure that these findings pertain to all breast cancer survivors.
Weight gain is a concern of many women after a diagnosis of breast cancer. In a community-based study (44
), the majority of breast cancer survivors were dissatisfied with their weight and stated that they were ready to take steps necessary to reduce their weight. A study conducted among 531 breast cancer survivors found that 52% wanted nutritional guidance at the time of diagnosis or soon after, although few reported having ever received dietary recommendations from their physicians (45
In conclusion, over two-thirds of women in our study gained weight and body fat within the first three years after a diagnosis of breast cancer, and to a greater degree than that previously reported in studies of healthy women. Weight and body fat gains were greatest in women who reported less participation in physical activity. Since higher levels of body fat are associated with increased breast cancer recurrence and decreased survival, it is imperative that research be conducted on the prognostic effect of physical activity and weight loss in overweight and obese breast cancer survivors.