Suche
Mein Konto
This article is part of the 2019 Oncology Special IssueJournal of naturopathy. Read the full issue here.
Relation
N. Zheng, E. Hsieh, H. Cai et al. Soy food consumption, exercise and body mass index and osteoporosis fracture risk in breast cancer survivors: the Shanghai Breast Cancer Survival Study. (Link removed). 2019;3(2):1-8.
Study objective
Assessing the Associations Between Soy Diet Intake, Exercise and BMI and Osteoporosis-Related Fractures in Women With a History of Breast Cancer (Stages 0-III)
Draft
Population-based longitudinal study (Shanghai Breast Cancer Survival Study)
Participant
The participants are part of the ongoing Shanghai Breast Cancer Survival Study. A total of 4,139 women, all with a diagnosis of breast cancer (stage 0-III), were examined (1,987 women were pre-/perimenopausal, 2,152 women were postmenopausal).
Study parameters assessed
Osteoporosis-related bone fractures were evaluated 18 months and 3, 5, and 10 years after diagnosis. Exercise and soy isoflavone intake were assessed 6 and 18 months after diagnosis. Weight and height were recorded at baseline.
Primary outcome measures
Outcome measures were the number of osteoporotic fractures, defined as “fractures caused by falls from standing height and at sites associated with osteoporosis” in relation to menopausal status, soy intake, and BMI.
Key insights
The overall risk of osteoporotic fractures was 2.9% for pre-/perimenopausal women and 4.4% for postmenopausal women, respectively. High intake of soy isoflavones was associated with a lower fracture risk for pre-/perimenopausal women, but not for postmenopausal women. Specifically, pre-/perimenopausal women consuming >56.06 mg/d isoflavones had a significantly lower risk of fracture (hazard ratio [HR]: 0.22, 95% confidence interval [CI]: 0.09-0.53) compared to pre-/perimenopausal women consuming <31.31 mg/d (P25 kg/m2) was associated with a higher risk of fracture (HR: 1.81, 95% CI: 1.04-3.14) for pre-/perimenopausal women, but overweight/obesity was not an associated risk for the postmenopausal cohort. Exercise was inversely associated with osteoporotic fractures in postmenopausal women (HR: 0.56, 95% CI: 0.33–0.97 for metabolic equivalent hours > 12.6 vs < 4.5), and exercise followed a dose-response pattern (Ptrend=0.035).
Practice implications
The risk of osteoporosis and bone fractures increases in women diagnosed with estrogen receptor-positive breast cancer.1Selective estrogen receptor modulators (SERMs, such as tamoxifen) for pre-/perimenopausal women and aromatase inhibitors for postmenopausal women lead to a reduction in the estrogenic environment in bone.2-7The publication currently under review is the first to suggest that higher isoflavone intake is associated with fewer osteoporotic fractures in pre-/perimenopausal women. This study also confirms that exercise is inversely associated with fracture risk in a dose-dependent manner.
Osteoporosis and the risk of fractures associated with reduced bone mineral density (BMD) are a consequence of several other types of cancer therapies. Androgen deprivation, stem cell transplantation, and ovarian failure secondary to chemotherapy treatment are all associated with treatment-induced bone loss.8Primary care physicians are often tasked with monitoring bone health in many of these patient populations because oncology standards of care often do not provide such guidance.
In bone, estrogen has a protective effect against loss of BMD. When estrogen binds to its receptor, osteoclast activity decreases; therefore, anything that limits estrogenic effects in bone results in greater osteoclastic activity and a reduction in BMD. Antiestrogenic drugs that generally lower estrogen, such as aromatase inhibitors, reliably lead to bone loss through this mechanism. Similarly, premenopausal women who undergo ovarian ablation due to medication or surgery lose the bone-protective effects of their endogenous estrogens.
In contrast to aromatase inhibitors, which generally reduce estrogen by >95%,9SERMs have a different effect on estrogen receptors, either as aOpponentor aagonist, depending on the tissue/organ. Tamoxifen, the most widely used SERM, is an antagonist when bound to estrogen receptors in breast tissue while having a mild effectagonistEffect on binding to receptors in bone.10This mild agonist effect results in increased BMD in postmenopausal women taking tamoxifen.11However, premenopausal women taking tamoxifen will not achieve this benefit. Premenopausal endogenous estrogens still circulate at relatively high concentrations, making the weak agonist effect of tamoxifen a net reduction in estrogenic effects on bone.12
The publication currently under review is the first to suggest that higher isoflavone intake is associated with fewer osteoporotic fractures in pre-/perimenopausal women.
While isoflavones are commonly referred to as phytoestrogens, they are more similar to “phyto-SERMs,” with effects that depend on the estrogen receptors (alpha/beta) expressed as well as the tissue type.13Previous studies of isoflavone intake from soy foods in women with a history of breast cancer have suggested an inverse association with recurrence as well as all-cause mortality.14-19We know less about high-dose, isolated soy isoflavones; Experimental studies suggest that isoflavones as isolates have unique risks at high doses and no evidence of safety exists.20
Given that this study tracked consumption of isoflavones from whole foods, it is possible that other components in soy are responsible for the reduced risk of osteoporotic fractures observed in premenopausal women. In the current study, an associated decrease in osteoporotic fractures was absent in the postmenopausal cohort, further suggesting the presence of non-estrogen-mediated mechanisms. Like any plant, soy contains a complex spectrum of thousands of phytochemicals. For example, flavonoids derived from soy have dozens of known physiological effects, although none of them alone can explain the bone health observation observed in the current study.20
This study was conducted in China, where consumption of soy foods is dramatically higher than in Western populations. The intake of isoflavones per day in the Shanghai Breast Cancer Survival Study had a mean [SD] value of 45.9 [38.3]. In comparison, in the Women's Healthy Eating and Living (WHEL) study, a US-based cohort examining soy consumption in women with a history of breast cancer, the mean [SD] intake was 2.6 [7.9] mg. In the Life After Cancer Epidemiological (LACE) study, women consumed a mean [SD] 4.1 [11.9] milligrams per day.16While these studies showed an association between the benefits of soy consumption and breast cancer mortality and recurrence at these low levels, it is unclear whether the effects even translate to bone health.
There are several limitations of this study, as described by the authors: Data collection was dependent on self-reports of osteoporotic fractures, which were considered reliable but inherently carry the risk of misclassification. Information on osteoporosis screening, bisphosphonate use, or adherence to osteoporosis prevention guidelines was also not collected. This study used data before the widespread introduction of bone health monitoring in women with a history of breast cancer in China. Similarly, bisphosphonate use was unlikely, although possible, given the years of enrollment in this study from 2002 to 2006.
There is no doubt that bone health is a top priority in women with a history of breast cancer and that active surveillance with sequential bone density scans should occur over time. Given the preponderance of evidence that a whole food soy diet can benefit these women, we now have another reason to reassure them that a serving or two of soy is not only okay, but recommended. While studies on soy do not differentiate between conventional and organic sources, it goes without saying that organic sourcing is advisable.