Abstract
In previous studies of postmenopausal women, overall intake of fruits and vegetables groups has been inversely associated with estrogen receptor negative (ER−) breast cancer. In this analysis, we prospectively examined the associations of specific fruits and vegetables with risk of ER− postmenopausal breast cancer among 75,929 women aged 38 to 63 years at baseline and followed for up to 24 years. Dietary data were collected seven times during this period. Cox proportional hazard models were used, adjusting for potential confounders, including a modified Alternate Mediterranean Diet score. We ascertained 792 incident cases of ER− post-menopausal breast cancer. The multivariate relative risk (RR) for every 2 servings/week consumption for total berries was 0.82 (95% CI=0.71–0.96, p=0.01), and the RR for women who consumed at least one serving of blueberries a week was 0.69 (95% CI=0.50–0.95, p=0.02) compared with non-consumers. Also, the RR for consuming at least 2 servings of peaches/nectarines per week was 0.59 (95% CI=0.37–0.93, p = 0.02). Risk of ER− breast cancer was not associated with intakes of other specific fruits or vegetables. In conclusion, higher intake of berries and peaches was associated with lower risk of ER− breast cancer among post-menopausal women. These results are considered exploratory and need to be confirmed in further studies.
Introduction
The potential for fruits and vegetables in breast cancer prevention has been studied frequently. In a recent pooled analysis, higher intakes of total fruits and vegetables, and vegetables, but not fruits, were associated with a lower risk of estrogen receptor negative (ER−) but not ER+ breast cancer [1]. In an earlier analysis among post menopausal women in the Nurses’ Health Study, we found that the association with fruits and vegetables was also limited to estrogen receptor negative breast cancer [2] and this was confirmed in the Black Women’s Health Study [3]. In recent pooled analyses of dietary carotenoids [4] or blood carotenoid measurements [5], inverse association were also much stronger with or limited to ER− breast cancer. However, specific fruits and vegetables vary greatly in their composition and are not likely to have identical relationships with breast cancer. Although the pooled analysis did examine individual fruits and vegetables and observed inverse association with peaches and strawberries, the number of specific fruits and vegetables was limited to items measured in multiple cohorts. Berries, in particular blueberries, are rich in antioxidants and polyphenols [6] and may influence breast cancer risk, yet were not examined in the pooled analysis. Thus, we prospectively examined associations between specific fruits and vegetables and risk of ER− breast cancer among post-menopausal women in the Nurses’ Health Study. Our detailed food frequency questionnaire allowed us to examine 29 different fruits and vegetables, including blueberries.
Subjects and Methods
Study Population
The Nurses’ Health Study (NHS) is a cohort study of 121,700 female nurses aged 30–55 years living in 11 U.S. states established in 1976. Questionnaires are sent biennially to collect medical, lifestyle, and other health-related information [7]. In 1980, participants completed a 61-item food frequency questionnaire (FFQ). This was expanded to 116 items in 1984 and similar FFQs were sent in 1986, 1990, 1994, 1998, 2002, and 2006.
For this analysis, we used 1984 as baseline as the expanded FFQ provides more detailed information on consumption of fruits and vegetables. We included women who completed the 1984 FFQ with plausible total energy intake (calculated from the FFQ, between 500 and 3500 kcal/day) [8]. After excluding those with a history of cancer (except non-melanoma skin cancer) at baseline, we included 75,929 post-menopausal women with follow-up from 1984 through 2008. This study was approved by the Institutional Review Board of the Brigham and Women's Hospital, Boston, MA.
Dietary Assessment
Self-administered semi-quantitative FFQs were designed to assess average food intake over the preceding year. A standard portion size and nine possible consumption frequency categories, from “never, or <1/month” to “6+ times per day” were given for each food. Total energy and nutrient intake were calculated by summing the contributions from all foods. Previous validation studies in the NHS revealed reasonably good correlations between energy-adjusted nutrients and foods assessed by the FFQ and multiple food records completed over the preceding year [9]. The corrected correlation coefficients for fruits and vegetables between diet records and food frequency questionnaire ranged from 0.16 for winter squash to 0.74 for apples. The corrected correlation coefficients for most fruits and vegetables were above 0.40.
Breast cancer ascertainment
Incident breast cancer was ascertained from 1984 to 2008, a follow-up of up to 24 years. In each biennial questionnaire, participants self-report any diagnosis of breast cancer in the previous 2 years. We then obtained permission to review medical records for confirmation, and we confirmed 99% of the cases for which records were available. Estrogen and progesterone receptor status was obtained from pathology reports and each receptor was classified as positive, negative, or uncertain. Deaths were reported by the postal service, family members, or by searching the National Death Index. In this study, as in our previous report, we included only postmenopausal breast cancer cases to reduce potential etiologic heterogeneity.
Measurement of lifestyle and health factors
Body mass index (BMI) was calculated from weight reported on each biennial questionnaire and height reported on the first questionnaire. Smoking, history of hypertension, aspirin use, multivitamin intake, menopausal status and use of postmenopausal hormone therapy, history of benign breast disease, parity, and age at first birth were assessed every 2 years. Family history of breast cancer was assessed six times during follow-up. Leisure-time physical activity was measured with validated questions on 10 common activities beginning in 1986 [10]. In 1984, we collected hours of vigorous physical activity.
Statistical analysis
We used Cox proportional hazard models to assess the association between intake of specific fruits and vegetables and risk of postmenopausal ER− breast cancer between 1984 and 2008. To reduce random within-person variation and to best represent long-term dietary intake, we calculated cumulative averages of intake from our repeated FFQs [11]. Potatoes were not included as a vegetable in any of our analysis. Because legumes are sources of protein and not generally viewed as vegetables in meal planning, we combined all other vegetables without legumes as low protein vegetables. Groups of fruits and vegetable were classified into quintiles of intake with the first quintile as a reference. For specific fruits and vegetables, we computed the relative risk for every 2 servings/week increase of intake.
In multivariate analysis, we adjusted for age, energy intake (quintiles), alcohol (4 categories), multivitamin use (yes/no), BMI at age 18 (5 categories), weight change since age 18 (7 categories), family history of breast cancer (yes/no), history of benign breast disease (yes/no), physical activity in METs (quintiles), and age at menopause and post-menopausal hormone use (11 categories). We also adjusted for a modified Alternative Mediterranean Diet score in which we excluded fruits and vegetables to avoid redundancy with our primary variables [2]. Statistical adjustment was updated for covariates measured more than once during follow-up.
Results
Women with high intakes of fruits and vegetables were more physically active, and were less likely to be current smokers, but no apparent trend was observed with BMI (table 1). These women also consumed less alcohol and saturated fat but more fiber and folate.
Table 1.
Age standardized baseline (1984) characteristics according to quintile of total fruits and vegetables intake1
| Q1 | Q2 | Q3 | Q4 | Q5 | |
|---|---|---|---|---|---|
| median intake (servings/d) | 2.4 | 3.9 | 5.1 | 6.5 | 9.8 |
| BMI | 24.6 | 24.7 | 24.6 | 24.8 | 24.7 |
| Current smokers (%) | 38 | 30 | 25 | 22 | 18 |
| Physical activity (hrs/wk) | 2.5 | 2.7 | 2.8 | 2.9 | 3.1 |
| Family history (%) | 9 | 9 | 9 | 9 | 10 |
| Alcohol (g/d) | 8 | 7 | 7 | 7 | 6 |
| Polyunsaturated fat (g/d) | 12 | 12 | 12 | 12 | 11 |
| Monounsaturated fat (g/d) | 24 | 23 | 22 | 22 | 20 |
| Saturated fat (g/d) | 24 | 23 | 22 | 21 | 19 |
| Fiber (g/d) | 13 | 15 | 17 | 18 | 22 |
| Folic acid (mcg/d) | 315 | 364 | 390 | 426 | 486 |
| Glycemic load | 97 | 98 | 99 | 100 | 104 |
dietary factors are energy adjusted except for alcohol.
During 24 years of follow-up, we documented 792 cases of ER− post menopausal breast cancer. Intakes of total fruits plus vegetables and total vegetables were only marginally associated with lower risk of ER− breast cancer (table 2). On the other hand, there was no association with total fruits intake. When we explored the associations with individual fruits and vegetables, we noted a RR of 0.82 (95% CI=0.71–0.96, p=0.01) for an increment of 2 servings/week of berries (figure 1). When we separately examined strawberries and blueberries, the two berries item in our FFQ, the RR for every 2 servings/week for strawberries was 0.80 (95% CI=0.65–0.99, p=0.04), and for blueberries was 0.67 (95% CI=0.49–0.94, p=0.02). Intakes of blueberries and strawberries were moderately correlated (Spearman correlation coefficient = 0.47, p < 0.0001), when both were in the model, the relative risks were slightly attenuated and did not reach statistical significance (data not shown). Consumption of peaches and nectarines was also associated with a lower risk for ER− tumors (for every 2 servings/week consumption RR =0.82, 95% CI=0.70–0.97, p=0.02). Among vegetables, winter squash was the only vegetable that showed a marginal inverse association (RR for every 2 servings/week = 0.70, 95% CI=0.49–1.00) (figure 2).
Table 2.
Relative risks (95% CI) of estrogen receptor negative breast cancer by quintiles of fruits and vegetables intakes.
| Q1 | Q2 | Q3 | Q4 | Q5 | P trend | ||
|---|---|---|---|---|---|---|---|
| Total fruits and vegetables | |||||||
| Median servings/d | 3.1 | 4.3 | 5.5 | 6.8 | 9.1 | ||
| No. of cases | 158 | 149 | 184 | 146 | 155 | ||
| Age & energy adjusted | 1 | 0.87 (0.69, 1.09) | 1.01 (0.81, 1.26) | 0.77 (0.61, 0.98) | 0.78 (0.60, 0.99) | 0.06 | |
| Multivariate adjusted1 | 1 | 0.86 (0.69, 1.10) | 1.00 (0.80, 1.27) | 0.80 (0.62, 1.03) | 0.82 (0.62, 1.08) | 0.13 | |
| Total vegetables2 | |||||||
| Servings/d | 1.7 | 2.6 | 3.3 | 4.1 | 5.6 | ||
| No. of cases | 154 | 166 | 172 | 158 | 142 | ||
| Age & energy adjusted | 1 | 1.01 (0.81, 1.26) | 1.00 (0.80, 1.25) | 0.89 (0.71, 1.13) | 0.77 (0.60, 0.98) | 0.047 | |
| Multivariate adjusted1 | 1 | 1.01 (0.80, 1.26) | 1.02 (0.83, 1.28) | 0.91 (0.71, 1.17) | 0.81 (0.61, 1.06) | 0.06 | |
| Total low protein vegetables2 | |||||||
| Servings/d | 1.6 | 2.4 | 3.1 | 3.9 | 5.3 | ||
| No. of cases | 160 | 164 | 167 | 157 | 144 | ||
| Age & energy adjusted | 1 | 0.97 (0.78, 1.11) | 0.94 (0.75, 1.17) | 0.86 (0.68, 1.08) | 0.76 (0.59, 0.96) | 0.049 | |
| Multivariate adjusted1 | 1 | 0.96 (0.77, 1.21) | 0.95 (0.75, 1.19) | 0.87 (0.68, 1.11) | 0.79 (0.60, 1.03) | 0.05 | |
| Total fruits | |||||||
| Servings/d | 0.9 | 1.6 | 2.2 | 2.8 | 3.9 | ||
| No. of cases | 145 | 142 | 170 | 182 | 153 | ||
| Age & energy adjusted | 1 | 0.91 (0.72, 1.15) | 1.05 (0.83, 1.32) | 1.07 (0.85, 1.34) | 0.86 (0.67, 1.11) | 0.30 | |
| Multivariate adjusted1 | 1 | 0.91 (0.72, 1.15) | 1.06 (0.83, 1.34) | 1.11 (0.87, 1.41) | 0.93 (0.71, 1.21) | 0.85 | |
adjusted for age, energy intake, smoking, alcohol, weight change since age 18, height, postmenopausal hormone use, physical activity, BMI at age 18, family history, history of benign breast disease, modified Alternate Mediterranean Diet score
exclude potatoes
excludes legumes and potatoes
Figure 1.
Multivariate1 relative risks for estrogen receptor negative breast cancer of specific fruits for every 2 servings/week intake.
Error bars represent 95% confidence interval
1 adjusted for age, energy intake, smoking, alcohol, weight change since age 18, height, postmenopausal hormone use, physical activity, BMI at age 18, family history, history of benign breast disease, modified Alternate Mediterranean Diet score.
Figure 2.
Multivariate1 relative risks for estrogen receptor negative breast cancer specific of vegetables for every 2 servings/week intake.
Error bars represent 95% confidence interval
1 adjusted for age, energy intake, smoking, alcohol, weight change since age 18, height, postmenopausal hormone use, physical activity, BMI at age 18, family history, history of benign breast disease, modified Alternate Mediterranean Diet score.
When we examined categories of intakes for foods that were significant in continuous analyses, we observed the clearest trends with blueberries and peaches (table 3). Compared to women who did not consume blueberries, those with greater than 1/week intake, the RR for post-menopausal ER− breast cancer was 0.69 (95% CI=0.50–0.95, p =0.02). For peaches, women who consumed at least 2 servings of peaches at week had an RR of 0.59 (95% CI=0.37–0.93, p = 0.02).
Table 3.
Multivariate* relative risks (95% CI) for selected fruits intake
| Never | Up to 2/month | > 2/month to <1/week |
> 1+/week | 1/week to <2/week | 2+/week | p trend | |
|---|---|---|---|---|---|---|---|
| Total berries | |||||||
| No. of cases | 59 | 232 | 184 | 283 | 34 | ||
| Person years | 100,500 | 330,065 | 234597 | 484,552 | 71,322 | ||
| Multivariate RR | 1 | 1.04 (0.78, 1.40) | 1.11 (0.81, 1.50) | 0.87 (0.65, 1.17) | 0.75 (0.49, 1.16) | 0.01 | |
| Strawberries | |||||||
| No. of cases | 63 | 353 | 213 | 142 | 21 | ||
| Person years | 114,010 | 496,968 | 288904 | 283,880 | 37,276 | ||
| Multivariate RR | 1 | 1.14 (0.86, 1.50) | 1.12 (0.83, 1.50) | 0.81 (0.59, 1.10) | 1.02 (0.62, 1.69) | 0.04 | |
| Blueberries | |||||||
| No. of cases | 326 | 352 | 75 | 39 | |||
| Person years | 268,245 | 282,908 | 81,907 | 44,866 | |||
| Multivariate RR | 1 | 1.00 (0.85, 1.17) | 0.79 (0.60, 1.03) | 0.69 (0.50, 0.95) | 0.02 | ||
| Peaches/nectarines | |||||||
| No. of cases | 74 | 306 | 165 | 220 | 27 | ||
| Person years | 118,385 | 445,096 | 233,514 | 353,017 | 71,025 | ||
| Multivariate RR | 1 | 1.00 (0.77, 1.29) | 0.98 (0.73, 1.30) | 0.87 (0.66, 1.15) | 0.59 (0.37, 0.93) | 0.02 |
adjusted for age, energy intake, smoking, alcohol, BMI, weight change since age 18, height, postmenopausal hormone use, physical activity, BMI at age 18, family history, history of benign breast disease
Discussion
Because of previous suggestions that intakes of fruits and vegetables may be inversely associated with risk of ER− breast cancer, we conducted an exploratory analysis to identify specific foods that might account for this relationship. We observed inverse associations between intakes of blueberries, strawberries, and peaches/nectarines.
In an earlier meta-analysis, a weak inverse association was seen between intake of fruits and vegetables combined and overall breast cancer risk but this analysis did not differentiate cases by hormone receptor status [12]. In a recent pooled analysis that included hormone receptor status, greater intake of total vegetables, excluding potatoes and beans, was significantly associated with a lower risk of ER− breast cancer [1]. Although not statistically significant, in our analysis we found a similar relative risk for the group of foods. In addition, in two recent pooled analyses both dietary [13] and circulating [5] carotenoids were inversely associated primarily with risks of ER− tumors. Collectively these finds strongly suggest that higher intakes of fruits and vegetables reduce the risk of ER− breast cancer.
In an examination of specific foods within the recent pooled analysis of prospective studies, which included the Nurses’ Health Study [1], intakes of apples/pears, peaches/nectarines/apricots, and strawberries, carrots, and lettuce/salad were associated with lower incidence of ER− breast cancer. Our results for peaches and strawberries agreed with the pooled analysis [1], and showed similar magnitude of risk reduction. Blueberries were not included in the pooled analysis because few other studies collected data on consumption, and to our knowledge, this is the first human report on blueberries and breast cancer. The greater power of the pooled analysis likely accounted for the statistically significant inverse associations with apples/pears, carrots and lettuce that were not seen in this analysis. In our previous report, consumption of yellow/orange vegetables was associated with lower risk of ER− tumors [2]. In the Shanghai Breast Cancer Study, which was not included in the Pooling Project, higher intakes of citrus was significantly and rosaceae fruits (e.g. apples and peaches) were associated with a lower risk of ER-/PR- tumors [14].
Both strawberry and blueberry extracts have shown to reduce growth in breast cancer cell lines [15–17]. In mice, strawberries extract has reduced tumor progression by enhancing apoptosis[18]. In addition, one study showed quercetin and cholorogenic acid extracted from peaches reduced proliferation in estrogen-independent breast cancer cell lines [19]. Fruits and vegetables may also reduce breast cancer risk as sources of antioxidants [20, 21].
The large number of postmenopausal breast cancer during 24 years of follow-up allowed us to examine specifically ER− tumors, which have been inversely associated with intake of fruits and vegetables. We have extensive information on potential confounders which we carefully controlled for in our analysis. Although error in assessment of long term diet was reduced by many repeated measure, some degree of error is unavoidable as diet and lifestyle information was obtained through self report.
In conclusion, we observed a lower risk for ER− tumors with higher intake of berries and peaches. Our finding of lower risks with higher intake of blueberries needs to be confirmed in other populations.
Acknowledgement
Funding source: NIH grants CA87969, HL60712, CA95589, and 1U54CA155626-01 We would like to thank the participants and staff of the Nurses' Health Study, for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY
Footnotes
Conflict of interest:
The authors declare that they have no conflict of interest.
References
- 1.Jung S, Speigelman D, Baglietto L, Bernstein L, Boggs DA, van den Brandt PA, et al. Fruit and Vegetables Intake and Risk of Breast Cancer by Hormone Receptor Status. Journal of the National Cancer Instutitue. 2013;105:219–236. doi: 10.1093/jnci/djs635. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Fung TT, Hu FB, McCullough ML, Newby PK, Willett WC, Holmes MD. Diet quality is associated with the risk of estrogen receptor-negative breast cancer in postmenopausal women. J Nutr. 2006 Feb;136(2):466–472. doi: 10.1093/jn/136.2.466. PubMed PMID: 16424129. Epub 2006/01/21. eng. [DOI] [PubMed] [Google Scholar]
- 3.Boggs DA, Palmer JR, Wise LA, Spiegelman D, Stampfer MJ, Adams-Campbell LL, et al. Fruit and vegetable intake in relation to risk of breast cancer in the Black Women's Health Study. American Journal of Epidemiology. 2010;172:1268–1279. doi: 10.1093/aje/kwq293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Zhang X, Spiegelman D, Baglietto L, Bernstein L, Boggs DA, van den Brandt PA, et al. Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status: a pooled analysis of 18 prospective cohort studies. American Journal of Clinical Nutrition. 2012;95:713–725. doi: 10.3945/ajcn.111.014415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Eliassen AH, Hendrickson SJ, Brinton LA, Buring JE, Campos H, Dai Q, et al. Circulating Carotenoids and Risk of Breast Cancer: Pooled Analysis of Eight Prospective Studies. Journal of the National Cancer Instutitue. 2012;104:1905–1916. doi: 10.1093/jnci/djs461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Johnson SA, Arjmandi BH. Evidence for Anti-Cancer Properties of Blueberries: A Mini-Review. Anticancer Agnest in Medicinal Chemistry. 2013 doi: 10.2174/18715206113139990137. Epub Jan 24. [DOI] [PubMed] [Google Scholar]
- 7.Colditz GA, Martin P, Stampfer MJ, Willett WC, Sampson L, Rosner BA, et al. Validation of questionaire information on risk factors and disease outcomes in a prospetive cohort of women. American Journal of Epidemiology. 1986;123:894–900. doi: 10.1093/oxfordjournals.aje.a114319. [DOI] [PubMed] [Google Scholar]
- 8.Willett WC. Nutritional Epidemiology. New York: Oxford Univeristy Press; 1998. [Google Scholar]
- 9.Salvini S, Hunter DJ, Sampson L, Stampfer MJ, Colditz GA, Rosner BA, et al. Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. International Journal of Epidemiology. 1989;18:858–867. doi: 10.1093/ije/18.4.858. [DOI] [PubMed] [Google Scholar]
- 10.Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, et al. Compendium of physical activities: an update of activity codes and MET intensities. Medicine and Science in Sports and Exercise. 2000;32(9 Suppl):S498–S504. doi: 10.1097/00005768-200009001-00009. [DOI] [PubMed] [Google Scholar]
- 11.Hu FB, Stampfer MJ, Rimm E, Ascherio A, Rosner BA, Spiegelman D, et al. Dietary fat and coronary heart disease: a comparison of approaches for adjusting for total energy intake and modeling repeated dietary measurements. American Journal of Epidemiology. 1999;149:531–540. doi: 10.1093/oxfordjournals.aje.a009849. [DOI] [PubMed] [Google Scholar]
- 12.Aune D, Chan DS, Vieira AR, Rosenblatt DA, Vieira R, Greenwood DC, et al. Fruits, vegetables and breast cancer risk: a systematic review and meta-analysis of prospective studies. Breast Cancer Research and Treatment. 2012;134:479–493. doi: 10.1007/s10549-012-2118-1. [DOI] [PubMed] [Google Scholar]
- 13.Zhang X, Speigelman D, Baglietto L, Bernstein L, Boggs DA, van den Brandt PA, et al. Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status: a pooled analysis of 18 prospective cohort studies. American Journal of Clinical Nutrition. 2012;95:713–725. doi: 10.3945/ajcn.111.014415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Bao PP, Shu XO, Zheng Y, Cai H, Ruan ZX, Gu K, et al. Fruit, vegetable, and animal food intake and breast cancer risk by hormone receptor status. Nutrition and Cancer. 2012;64:806–819. doi: 10.1080/01635581.2012.707277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Faria A, Pestana D, Teixeira D, de Freitas V, Mateus N, Calhau C. Blueberry anthocyanins and pyruvic acid adducts: anticancer properties in breast cancer cell lines. Phytotherapy Research. 2010;24:1862–1869. doi: 10.1002/ptr.3213. [DOI] [PubMed] [Google Scholar]
- 16.Adams LS, Phung S, Yee N, Seeram NP, Li L, Chen S. Blueberry phytochemicals inhibit growth and metastatic potential of MDA-MB-231 breast cancer cells through modulation of the phosphatidylinositol 3-kinase pathway. Cancer Research. 2010;70:3594–3605. doi: 10.1158/0008-5472.CAN-09-3565. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Wedge DE, Meepagala KM, Magee JB, Smith SH, Huang G, Larcom LL. Anticarcinogenic Activity of Strawberry, Blueberry, and Raspberry Extracts to Breast and Cervical Cancer Cells. Journal of Medical Foods. 2001;4:49–51. doi: 10.1089/10966200152053703. [DOI] [PubMed] [Google Scholar]
- 18.Somassagara RR, Hegde M, Chiruvella KK, Musini A, Choudhary B, Raghavan SC. Extracts of strawberry fruits induce intrinsic pathway of apoptosis in breast cancer cells and inhibits tumor progression in mice. PLoS One. 2012;7:e47021. doi: 10.1371/journal.pone.0047021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Noratto G, Porter W, Byrne D, Cisneros-Zevallos L. Identifying peach and plum polyphenols with chemopreventive potential against estrogen-independent breast cancer cells. Journal of Agriculture and Food Chemistry. 2009;57:5219–5226. doi: 10.1021/jf900259m. [DOI] [PubMed] [Google Scholar]
- 20.Tamini RM, Hankinson SE, Campos H, Spiegelman D, Zhang S, Colditz GA, et al. Plasma carotenoids, retinol, and tocopherols and risk of breast cancer. American Journal of Epidemiology. 2005;161:153–160. doi: 10.1093/aje/kwi030. [DOI] [PubMed] [Google Scholar]
- 21.Sato R, Helzlsouer KJ, Alberg AJ, Hoffman SC, Norkus EP, Comstock GW. Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. Cancer Epidemiology, Biomarkers & Prevention. 2002;11:451–457. [PubMed] [Google Scholar]