Impact of Lifestyle Factors on Prognosis Among Breast Cancer Survivors in the USA

Rachel E Ellsworth; Allyson L Valente; Craig D Shriver; Barry Bittman; Darrell L Ellsworth

Disclosures

Expert Rev Pharmacoeconomics Outcomes Res. 2012;12(4):451-464. 

In This Article

Diet & Breast Cancer Prognosis

Dietary Fat, Fiber, Fruit & Vegetable Intake

The Nurses' Health Study (NHS) was established in 1976 to follow 121,700 female nurses over time through periodic health assessment questionnaires. Food frequency data from 1982 NHS participants with invasive breast cancer collected over 10 years showed no association between dietary fat intake and mortality (Table 1).[19] The NHS investigators classified dietary patterns as prudent (high in fruits, vegetables, legumes, whole-grains and seafood) or Western (characterized by high amounts of refined grains, processed red meat, eggs and high-fat dairy products).[20] Among 2619 women with dietary data and a diagnosis of invasive breast cancer, those consuming a Western diet before and after diagnosis had a higher risk of all-cause mortality; however, diet did not impact breast cancer prognosis.[21] Additional research from the NHS showed no relationship between diet quality ­indices and breast cancer mortality.[22]

A second large, prospective cohort study, the LACE study, enrolled 2321 women from a California-based health-maintenance organization and the Utah cancer registry who were diagnosed with breast cancer between 1997 and 2000. Dietary intake of more than 100 foods, beverages, nutritional supplements and medicinal herbs was assessed by food frequency questionnaires. Preliminary data suggested that dietary patterns of women with breast cancer were similar to those in women free from breast cancer in the general population.[23] Similar to the NHS study, a Western diet was associated with an increased risk of all-cause mortality, but was not associated with breast cancer mortality.[24]

In the HEAL study, a significant number of African American and Hispanic participants were recruited from California (USA), Washington (USA) and New Mexico (USA). Women (n = 670) with early-stage breast cancer who consumed a better-quality diet (low in calories, added sugar, alcohol and saturated fat) had a 60% lower risk of all-cause mortality and an 88% lower risk of breast cancer-related mortality.[25] A quality diet was also associated with decreased levels of circulating inflammatory markers.[26] A recent report presented suggestive evidence that high dietary fiber consumption may be associated with reduced breast cancer events and total mortality, but results were not statistically significant.[27]

In contrast to the observational studies described above, the WINS is a randomized trial measuring the effects of a low-fat diet on relapse-free survival. Women in the intervention group (n = 975) undergoing standard treatment for stage I or II breast cancer followed a low-fat dietary intervention, while controls (n = 1462) received minimal nutrition counseling. The intervention group showed a significant decrease in fat intake and maintained lower fat consumption for more than 5 years, while patients in the control group showed no significant change in fat intake. After 60 months of follow-up, relapse-free survival was 24% higher in the intervention group overall; however, subgroup analysis detected more pronounced effects in women with hormone receptor-negative carcinomas, suggesting a differential influence of diet on breast cancer ­recurrence based on hormone receptor status.[28]

In the WHEL study, women with stage I–IIIA breast cancer were randomized to an intervention arm (n = 1537) or control arm (n = 1551). The intervention group consumed a high fruit and vegetable diet, with only 15–20% of calories from fat, while controls were advised to follow the 5-A-Day for Better Health Program diet recommended by the National Cancer Institute. Nutritional intake for both groups was similar at baseline, but after 4 years the intervention group increased vegetable consumption by 65%, fruit consumption by 25%, fiber consumption by 30% and decreased calories from fat by 13% compared with the control group. Despite improvements in nutrition, breast cancer event-free survival and mortality did not differ significantly between the intervention and control groups.[29]

Ethnic and geographic differences among patients may affect the relationship between diet and breast cancer prognosis. Recent studies indicate that breast cancer survivors from racially and ethnically diverse populations differ in levels of physical activity, long-term adherence to dietary interventions and rates of obesity,[30,31] which may predispose certain groups to recurrence or poor prognosis. The HEAL study was one of only a few large studies to detect an association between diet quality and breast cancer mortality, which may reflect an ethnically diverse patient ­population recruited from different geographic locations.

Alcohol

In a large meta-analysis that included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies, the relative risk of breast cancer increased by approximately 7% (95% CI: 5.5–8.7%, p < 0.00001) for each additional 10 g (unit or drink) of alcohol consumed on a daily basis.[32] However, relationships between alcohol consumption and breast cancer survival have not been well defined. One study of 1268 women ≤45 years of age with invasive breast cancer assessed the effect of prediagnostic alcohol consumption on mortality and determined that women who consumed alcohol during the 5-year period prior to diagnosis had a 30% decreased risk (hazard ratio: 0.7; 95% CI: 0.5–0.9) of breast-cancer-related mortality compared with nondrinkers.[33] Similarly, the population-based SEARCH study of 4560 breast cancer patients detected a 2% reduction in mortality risk for every unit of alcohol consumed per week.[34] In contrast, the LACE study detected a 1.3-fold increase in breast cancer recurrence and a 1.5-fold increase in mortality among overweight and obese women who had three to four alcoholic drinks per week.[35] Other studies have shown no relationship between alcohol consumption and survival.[36,37] Given the limitations of currently available data, a personal decision to consume alcohol should balance the protective effects of alcohol for cardiovascular health against the potential for increased breast cancer risk.[38]

Vitamins

Nearly 50% of adults in the USA use vitamin supplements, even though research has provided no convincing evidence of true beneficial effects.[39] At present, the US Preventive Services Task Force and the National Institutes of Health Office of Dietary Supplements and Office of Medical Applications do not recommend use of multivitamins for the prevention of chronic disease.[40,41] Furthermore, two large studies examining the impact of multivitamins on breast cancer risk, the Women's Health Study (WHS) and Women's Health Initiative (WHI), found that multi­vitamin use did not decrease the risk of developing breast cancer or influence overall mortality.[42,43]

Although multivitamin supplements do not appear to impact breast cancer risk, specific vitamins may have beneficial effects on prognosis in breast cancer survivors. One study showed that premenopausal survivors diagnosed with node-positive breast cancer and low levels of retinol-binding protein, the carrier for vitamin A in plasma, had early disease recurrence.[44] In a separate study of postmenopausal women, low vitamin A levels were associated with poor outcomes such as distant metastasis and increased mortality.[45] In a study of 516 postmenopausal women with breast cancer from Orange County (CA, USA), women with the highest folate intake had lower mortality risk and vitamin C was significantly associated with decreased all-cause mortality. Nutrients derived from diet, rather than supplements, were believed to provide the survival advantage.[46] In the LIBCSP (n = 1508 women), vitamins B1 and B3 were associated with a 46 and a 39% lower risk, respectively, of all-cause mortality. Vitamin B1 intake was associated with decreased breast cancer mortality.[47] In the Shanghai Breast Cancer Survivor Study of 4877 women with breast cancer, vitamin C intake was associated with a 44% decrease in all-cause mortality and a 38% decrease in breast cancer recurrence.[48] Finally, although one group found significantly higher levels of circulating 25-hydroxyvitamin D in women with early-stage disease compared with patients with locally advanced or metastatic breast cancer,[49] other studies suggest that vitamin D consumption following treatment may have no survival advantage.[50]

The American Cancer Society (ACS) currently recommends that survivors consider using multivitamins with 100% of the daily recommended values to ensure proper nutrition. Nearly 75% of breast cancer patients report taking multivitamins to bolster their immune system and make treatment more effective. The data presented here demonstrate that levels of specific vitamins, rather than multivitamin consumption, may affect breast cancer outcome, but it is unclear whether these vitamins should be derived through diet or supplements to be most beneficial.

Green Tea

Consumption of green tea has long been customary in Asia, but the purported health-promoting benefits of green tea have been recognized only recently in the USA. Green tea contains a number of active ingredients including polyphenols, which may confer antimutagenic, antidiabetic, antibacterial, anti-inflammatory or hypocholesterolemic advantages.[51] In studies evaluating the effects of green tea consumption in 427 Japanese breast cancer survivors with stage I or II disease, recurrence was 16.7% in women who consumed five or more cups of green tea per day compared with 24.3% in those consuming less than five cups per day. This protective effect was not observed in patients with stage III breast cancer.[52] Likewise, in a second study of 1160 Japanese women, consuming three or more cups of green tea each day was protective against recurrence in women with stage I disease but showed no effect in more advanced cases.[53] A meta-analysis of these datasets showed that increased green tea consumption (more than three cups per day) was inversely associated with breast cancer recurrence.[54]

One possible explanation for the limited protective effects of green tea on recurrence in patients with advanced breast cancer involves the inhibitory action of polyphenols on angiogenesis and invasion. Inhibiting angiogenesis and invasive potential may be more important in early-stage tumors, which must develop a network of blood vessels and have not yet formed successful metastases, than in late-stage tumors that already have an ­extensive blood vessel network and invasive characteristics.[55]

Little information exists on the relationship between green tea consumption and survival in US breast cancer patients. Thus far, studies of green tea and breast cancer have been performed mainly in Japanese populations where green tea is consumed routinely from an early age. It remains unclear whether health benefits observed in Japanese women will occur in women from other countries where lifetime consumption is much less.

Soy

A variety of health benefits have been attributed to consumption of soy-based foods, primarily due to soybean isoflavones such as genistein and diadzein. The chemical structure of isoflavones may enable these compounds to interact with human estrogen receptors, causing effects in the body similar to those induced by estrogen. Experimental studies in both cell lines and animal models suggest that genistein has the potential to stimulate cell proliferation, negatively influence prognosis and impair the effectiveness of tamoxifen therapy in estrogen receptor-positive breast carcinomas.[56,57]

Given the results of the experimental studies outlined above, which suggest that soy constituents can be estrogenic and potentially risk enhancing, an important question remains: do the estrogenic effects of soy influence prognosis and survival in humans? In population-based studies in the USA, women from the LIBCSP diagnosed with a first primary invasive breast carcinoma (n = 1210) showed reduced hazard ratios for all-cause mortality in the highest quintile of dietary intake compared with the lowest quintile for flavones, isoflavones and anthocyanidins. A decrease in breast cancer mortality was detected only in postmenopausal patients.[58] Other studies of diverse populations also observed significant inverse associations between soy consumption and breast cancer recurrence in postmenopausal women.[59,60] A recent meta-analysis observed that soy isoflavone consumption was inversely associated with breast cancer incidence and recurrence, but protective effects were only apparent in Asian ­populations, not in Western populations.[61]

Currently available data suggest that dietary intake of soy-based foods may confer a protective advantage for postmenopausal women with breast cancer; however, these benefits may be largely restricted to Asian populations where long-term soy intake is much higher. Additional health benefits, such as lower cholesterol and improved bone health, have been attributed to consumption of soy-based foods, but intake of isoflavones at high concentrations typically found in dietary supplements may be detrimental. Until the issue is fully resolved, physicians should allow patients receiving hormonal therapy or patients who have estrogen receptor-positive breast cancer to consume moderate amounts of soy as part of a balanced diet, but may recommend avoiding soy supplements.

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