Consuming more vegetables is associated with a lower risk of estrogen receptor (ER)-negative breast cancer, according to a new study published in the Journal of the National Cancer Institute. Researchers from Harvard Medical School did not observe a link between the total fruit and vegetable intake and overall risk of breast cancer or risk of ER-positive breast cancer.
Seungyoun Jung, ScD, of the Brigham and Women’s Hospital and Harvard Medical School, and colleagues analyzed more than 990,000 women in 20 cohort studies who were followed for 11 to 20 years. The researchers compared breast cancer outcomes among the groups who had the lowest and highest fruit and vegetable consumption.
The combined relative risk of the highest vs the lowest quartile of total vegetable intake was 0.82 for ER-negative breast cancer and 1.04 for ER-positive breast cancer (P < .001). Total fruit consumption was not statistically significantly associated with ER-negative breast cancer risk (0.94 relative risk). Analysis of specific fruits and vegetables showed a statistically significant inverse association for consumption of apples, pears, peaches, nectarines, apricots, strawberries, carrots, and lettuce with risk of ER-negative breast cancer.
Unlike ER-positive breast cancer, few risk factors have been identified for ER-negative breast cancer. Evidence that higher fruit and vegetable intake can lower overall breast cancer risk is inconclusive, but several smaller studies had shown that ER-negative breast cancer risk is lower with higher consumption. Because ER-negative breast cancer accounts for only 15% to 20% of all breast cancers, it is difficult to get a large enough cohort to assess significance. The current study is a large pooled cohort of women that were followed long-term and included many ER-negative breast cancer cases.
The biological mechanism of how components of fruits and vegetables may help to prevent ER-negative breast cancer is not clear. The authors suggest that the active compounds in vegetables and fruit may reduce the expression of epidermal growth factor receptor (EGFR), which is overexpressed in ER-negative breast cancers. Phytochemicals in vegetables have been suggested to lower the level of EGFR. The relevant parts of vegetables may be more concentrated in vegetables compared to fruit and more effective in preventing ER-negative cancer. The authors note that alpha-carotene, beta-carotene, and lutein/zeaxanthin (all of which are particularly abundant in vegetables) have each been inversely linked to the risk of ER-negative breast cancer in previous studies that used the same pooled cohorts as this study. A link was found for beta-cryptoxanthin, a component that is highly abundant in fruits, but it was not statistically significant.
“These findings support the value of examining etiologic factors in relation to breast cancer characterized by hormone receptor status in large pooled analyses because modest associations with less common breast cancer subtypes may have been missed in smaller studies,” state the authors.
Limitations of the study include the variability in reporting food intake and only a single measurement of fruit and vegetable consumption as a baseline reference. Additionally, 10 to 20 years may not be enough time to accurately assess consumption as breast cancer generally has a long duration time for development.
In an accompanying editorial, Cynthia A. Thomson and Patricia A. Thompson, of the College of Public Health at the University of Arizona, highlight that the authors of the study provide evidence, consistent across the 20 pooled studies, for the protective effect of fruit and vegetable consumption for ER-negative breast cancer. Thomson and Thompson also point out that ER-negative disease, and especially triple-negative breast cancer, is disproportionately associated with younger women, Hispanic and black women, and women in areas of low socioeconomic status. The increased risk among these women is thought to reflect different life choices and circumstances—higher parity, socioeconomic status, and not race or ethnicity.
The take-home message? “The findings support the emphasis of public messages for greater vegetable and selective fruit intake by extending a potential benefit for ER-negative breast cancer,” state the editorial authors. The challenge now is to reaffirm these findings in a larger and more diverse population.