The use of antioxidant supplements was associated with a 16% decreased risk of death from any cause. Vitamin C alone was associated with decreased risk of death from any cause. Vitamin E was associated with a decreased risk of recurrence.
Poole EM, Shu X, Caan BJ, et al. Postdiagnosis supplement use and breast cancer prognosis in the After Breast Cancer Pooling Project. Breast Cancer Res Treat. 2013;139(2):529-537.
The After Breast Cancer Pooling Project is a consortium of prospective studies on women with a history of breast cancer (stages I–IV). The prospective studies composing this consortium include the Shanghai Breast Cancer Survival Study, the Life After Cancer Epidemiological study (LACE), the Women’s Healthy Eating and Living (WHEL) study, and the Nurses’ Health Study (NHS). The total pool of participants contained 12,019 women.
Pooled statistical analysis of the above 4 prospective studies of women with a history of breast cancer
Associations of supplement usage with breast cancer recurrence, breast cancer mortality, and overall mortality were assessed.
The use of antioxidant supplements (multivitamins, vitamin C, or E) was associated with a 16% decreased risk of death from any cause (95% CI: 0.72–0.99). Vitamin C alone was associated with decreased risk of death from any cause (RR: 0.81; 95% CI: 0.72–0.92). Vitamin E was associated with a decreased risk of recurrence (RR: 0.88; 95% CI: 0.79–0.99). Vitamin D was associated with decreased risk of recurrence among ER positive, but not ER negative tumors (P-interaction=0.01). None of the supplements, alone or in combination, was associated with increased risk of recurrence or death. There were no statistically significant associations with breast cancer mortality specifically.
More than 2.8 million women in the United States have a history of breast cancer.1 Empowering women with tools they can use to lessen their risk of recurrence is essential. There is evidence that maintaining normal weight, physical activity, and a diet high in plant-based foods may lessen recurrence,2 and such measures should be the foundation of risk reduction for these patients. The current abstract suggests that there is some benefit to antioxidants taken as supplements, and concludes there is no increased risk with their use.
Until the last decade there was little prospective data to guide our understanding of how lifestyle factors or nutritional supplements may impact the recurrence of breast cancer. The After Breast Cancer Pooling Project (ABCPP) takes 4 ongoing prospective studies and combines the results in a systematic way to preserve the integrity of the data.3 So far, ABCPP has published in several key areas of modifiable risk habits. For example, alcohol intake is generally accepted as a maximum drink limit of 1 per day. Higher levels are associated higher risk of the initial diagnosis of breast cancer. According to ABCPP, associated risk of recurrence with alcohol intake is only relevant for women who are postmenopausal at the time of initial diagnosis.4 While there may be a trend, there is no statistical significance in premenopausal women. The authors concluded, “Overall, compared with nondrinking, regular alcohol intake (≥6.0 g/day) was not associated with risk of recurrence.”
However, postmenopausal women who regularly consumed alcohol (≥6.0 g/day) had an almost 20% increased risk of recurrence. There was no association with overall mortality in any groups. This level of consumption, which is essentially equivalent to 4 drinks daily, is much higher than other studies have reported. There is little offered as explanation for this surprisingly high level, but prudence and considerations for liver health alone would leave us recommending much lower consumption levels for proper health.
A surprising conclusion published by the ABCPP is that women who maintained their prediagnosis weight fared better than those who lost or gained weight.
Another unexpected outcome of all 4 studies separately, as well as in the combined data of the ABCPP, is that soy intake is not associated with any increase in risk of recurrence, all-cause mortality, or breast cancer mortality. While this information is many years old at the time of this writing, most of my patients are still hearing the old mantra, “Soy is estrogenic, so avoid it.” However, the ABCPP clearly disproves this assumption. They found that “isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined.” They found that consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92).”5 A review of soy consumption and recurrence of breast cancer was published in this journal and can be accessed here.
Another interesting conclusion that has come out of the ABCPP is the role of weight, as measured by BMI, on outcomes. They compared those who were underweight (BMI<18.5 kg/m2), normal weight (BMI 18.5–25 kg/m2), overweight (BMI 25–30 kg/m2), obese (BMI 30–35 kg/m2), severely obese (BMI 35–40 kg/m2) and morbidly obese (BMI >40 kg/m2). Using the BMI at time of diagnosis, the ABCPP concluded that there is a statistically significant increase in recurrence in women who are underweight (HR: 1.59; 95% CI: 1.18, 2.13) and morbidly obese (HR: 1.81; 95% CI: 1.42, 2.32). Those who were normal weight or overweight (BMI of 18.5–30 kg/m2) had the least recurrence, while the obese and severely obese had a slight increase that did not reach statistical significance. The morbidly obese women had higher risk of breast cancer–related mortality and overall mortality as well. The study’s authors concluded that the degree of obesity at time of diagnosis appears to confer differential risk on recurrence and mortality in women with a history of breast cancer.
It is not surprising that extremes on the weight spectrum have poorer prognosis. We can assume that those women are more likely to have comorbid conditions, be malnourished, are more sedentary, etc. This however, is all speculation. A surprising conclusion published by the ABCPP is that women who maintained their prediagnosis weight fared better than those who lost or gained weight. The researchers stratified 12,915 women with stages I–III cancer into 5 weight-change categories: within <5% loss or gain (reference); 5%–10% loss or gain, and ≥10% loss or gain. They concluded that stable weight in the early years post diagnosis is associated with the lowest overall mortality risk. “About 14.7% women lost and 34.7% gained weight…. Weight loss ≥10% was related to a 40% increased risk in the United States and over 3 times the risk of death in Shanghai.” The presence of comorbid conditions led to increased risk of death even in those who did lose weight. Whether the women intended to lose weight or not was not tracked or able to be determined from the studies. This is relevant for us as practitioners since we often give a lot of attention to normalizing weight with the assumption that this confers risk reduction. Indeed, a study earlier in 2013 concluded that risk was reduced with bringing BMI to less than 25 kg/m2.6 According to the results of ABCPP, perhaps more emphasis should be placed on managing or reversing comorbid conditions. With this in mind, the authors concluded, “Weight control strategies for breast cancer survivors should be personalized to the individual's medical history.”
While not “set in stone,” the size of the cumulative consortium of women with a history of breast cancer across these studies, along with the rigorous study designs, gives greater weight to the conclusions reached in the ABCPP than prior observational studies. Whether they substantiate or refute our assumptions about weight, alcohol intake, antioxidant usage, and/or soy consumption does not matter. The ABCPP conclusions deserve some extra weight in our minds when assessing the evidence simply because of the large number of women, the study designs (prospective studies designed to assess lifestyle factors), and the international cohorts. Given these factors, the conclusions drawn from the ABCPP are of clinical utility and relevant for a growing number of women in our practices.