An analysis of a large pooled data set from the Pooling Project of Prospective Studies of Diet and Cancer reported by Seungyoun Jung, ScD, Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues in Journal of the National Cancer Institute indicates that high fruit and vegetable consumption, particularly vegetable consumption, is associated with a significantly reduced risk of estrogen receptor (ER)-negative breast cancer.1 The analysis found no significant association between fruit and vegetable intake and risk of overall cancer or risk of ER-positive breast cancer.
Study Details
The study included prospectively collected data from 993,466 women followed for up to 11 to 20 years in 20 cohort studies. The primary analyses examined associations of fruit and vegetable intake with the risk of developing breast cancer subtypes defined by ER status, and secondary analyses evaluated associations with breast cancer subtypes defined by progesterone receptor (PR) status. Studies had to meet the following criteria to be included in the analyses: at least one publication on any diet and cancer association, comprehensive assessment of usual dietary intake, validation of the dietary assessment method or closely related instrument, and at least 25 incident breast cancer cases of the specific hormone receptor subtype being evaluated.
Overall, there were 34,526 incident invasive breast cancers diagnosed during follow-up in the population; hormone receptor status information was available for 24,673 cases, among which there were 19,869 ER-positive cancers, 4,821 ER-negative cancers, 16,162 PR-positive cancers, and 7,488 PR-negative cancers. Across studies, median fruit intake ranged from 118 to 392 g/d and median vegetable intake ranged from 61 to 259 g/d.
Reduced Risk for ER-negative Breast Cancer
In the multivariable analyses, there was no significant association of total fruit and vegetable, fruit, or vegetable intake with risk of total breast cancer. Total fruit and vegetable intake was associated with a significant reduction in risk for ER-negative breast cancer (P = .03 for trend; relative risk [RR] = 0.90 comparing the 5th vs 1st quintile). Total vegetable intake was significantly associated with an 18% lower risk of ER-negative breast cancer (P < .001), comparing the 5th vs 1st quintile. Fruit intake had a nonsignificant inverse association with risk of ER-negative breast cancer (P = .13; RR = 0.94 comparing 5th vs 1st quintile).
There was no significant association between fruit and vegetable, fruit, or vegetable intake and ER-positive breast cancer risk. (P ≥ .06 for trend; RR = 0.99–1.04 for these three food groups comparing 5th vs 1st quintile). There were no significant associations between fruit and vegetable, fruit, or vegetable intake and risk for PR-positive or PR-negative breast cancers.
When the fruit and vegetable intakes were modeled as continuous variables, the relative risks for ER-negative breast cancer for a 300-g/d increment (approximately three servings per day) were 0.94 (95% confidence interval [CI] = 0.91–0.98) for total fruits and vegetables, 0.88 (95% CI = 0.81–0.95) for vegetables, and 0.96 (95% CI = 0.91–1.00) for fruits. Intake of these three food groups was nonsignificantly associated with risk of ER-positive, PR-positive, and PR-negative breast cancer.
Adjustment for intake of beta-carotene, lutein, and fiber—which are concentrated in vegetables and thus could be driving the association between vegetable consumption and reduced ER-negative breast cancer risk—did not substantially change the inverse association observed between vegetable intake and ER-negative breast cancer risk.
Subtype Analysis by ER/PR Status
Multivariable analyses of joint ER and PR status showed no significant associations of total fruit and vegetable intake or fruit intake with any of the breast cancer subtypes defined jointly by ER/PR status. Higher vegetable intake was associated with a significant 16% reduction in risk for ER-negative/PR-negative breast cancer (P = .001 for trend; RR = 0.84 for 5th vs 1st quintile).
Analysis by Botanical Family and Specific Fruits and Vegetables
Analyses according to botanical taxonomy of fruits and vegetables showed that higher intake of the Rosaceae family (eg, apples, peaches) was significantly associated with reduced risk for ER-negative breast cancer (100-g/d increment, RR = 0.91). Nonsignificant inverse associations were observed for intake of Cruciferae (eg, broccoli, cabbage), Cucurbitaceae (eg, melon, squash), and Leguminosae (eg, beans, peas) families and risk of ER-negative breast cancer. No association was observed for intake of any of these families with risk of ER-positive breast cancers (RRs ranged from 1.00 to 1.04). Intake of Rutaceae (eg, grapefruits, oranges) and Solanaceae (eg, potatoes, tomatoes) was not associated with risk of either type of cancer.
Analyses of risks according to intake of specific fruits and vegetables showed significantly reduced risk of ER-negative breast cancer with increased intake of apples/pears (138 g/d increment, RR = 0.92), peaches/nectarines/apricots (87 g/d increment, RR = 0.81), strawberries (75 g/d increment, RR = 0.56), carrots (57 g/d increment, 0.92), and lettuce/salad (56 g/d increment, RR = 0.91), but no association with risk for ER-positive breast cancer.
No significant associations with risk for either ER-positive or ER-negative breast cancers were observed for intake of bananas, cantaloupe, grapefruit, oranges, fruit juice, broccoli, cabbage, spinach, tomatoes, yams, or potatoes.
Analysis by Participant Subgroups
Associations of fruit and vegetable, fruit, and vegetable intake with ER-positive and ER-negative breast cancer risk were also analyzed by participant subgroups, defined by menopausal status, postmenopausal hormone use, oral contraceptive use, multivitamin use, alcohol consumption, smoking status, body mass index, age at diagnosis, family history of breast cancer, and race. Although the differences in risk estimates across subgroups were not appreciably different, risk of ER-negative breast cancer was nonsignificantly reduced in most of the subgroups examined.
With regard to potential mechanisms for the reduced risk of ER-negative breast cancers with increased vegetable consumption, the authors speculated that the beneficial effect of bioactive compounds in vegetables may be more detectable in preventing the less hormonally dependent ER-negative tumors than ER-positive tumors. Epidermal growth factor receptor tends to be overexpressed in ER-negative breast tumors and this overexpression triggers nuclear factor-kappaB, which controls the transcription of DNA that is involved in immune responses. Further, the cell-cycle regulator cyclin E is overexpressed in ER-negative cancers.
The lesser effect of fruit consumption on risk may reflect greater preventive effectiveness of bioactive constituents that are more concentrated in commonly consumed vegetables.
The authors concluded, “[This analysis] provides compelling support for an association of high vegetable and fruit consumption, especially vegetable consumption, and reduced risk of ER-negative breast cancer. Our results support a beneficial effect of overall fruit and vegetable consumption rather than consumption of a few specific fruits and vegetables because associations were observed for several botanical families and several specific fruits and vegetables. In addition, when we controlled for several potential bioactive constituents concentrated in fruits and vegetables…, the inverse association for total vegetable consumption and risk of ER-negative breast cancer remained.” ■
Disclosure: This work was supported by grants from National Institute of Health and the Breast Cancer Research Foundation and a fellowship from Samsung Scholarship to Dr. Jung.
Reference
1. Jung S, Spiegelman D, Baglietto L, et al: Fruit and vegetable intake and risk of breast cancer by hormone receptor status. J Natl Cancer Inst 105:219-236, 2013.
