Vegetables and breast cancer.
Total breast cancer risk: Data about total vegetables in relation to total breast cancer risk was provided by a pooled analysis of 8 cohorts, and 8 additional
cohorts, including a total of 18,023 cases.
A weak significantly increased risk was found in one cohort of very large size, including 5,815 cases (George SM [38]). No other (non)significant associations were found.
The average RR = 1.00 (excluding incomplete data from Hirvonen T [29], Iwasaki M [20], Jarvinen R [11]).
Inclusion of intermediate levels of consumption:
(Non)significant effects at any level of consumption were as follows:
- Zhang S (4) Significant protective at 154-223, and ≥ 385 g/day among premenopausal women.
- van Gils CH (21) Significant protective at > 109-≤ 160 g/day.
- Sonestedt E (24) Significant protective at 218 g/day.
- George SM (38) Though the trend increased significantly, the risk increased nonsignificantly at ≥ 440 g/day.
Disease progression: Data about total vegetables in relation to disease progression was provided by 2 cohorts, including a total of 626 cases.
A nonsignificant protective effect against breast cancer recurrence among postmenopausal women was found in the smallest cohort (Hebert JR [12]), but no association was found
in the larger cohort (Pierce JP [35]). The average RR = 0.88
Breast cancer mortality: Results were included about a) breast cancer mortality, and b) all-cause mortality following diagnosis of breast cancer. If data about
both total mortality, and breast cancer-specific mortality were available following diagnosis of breast cancer, total mortality was chosen as end point.
Data about total vegetables in relation to breast cancer death was provided by 9 cohorts, including a total of 1,144 + X cases (no amount of cases was defined
for one cohort (Ewertz M [3]).
A significant protective effect was found in one cohort (McEligot AJ [31]), and nonsignificant effects were found in 3 other cohorts (Ewertz M [3], Holmes D [4],
Hebert JR [12]), including a total of 547 + X cases for all 4 cohorts combined (> 48% of all cases). No other (non)significant associations were found. The average
RR = 0.90 (excluding incomplete data from Goodwin PC [23], Ingram D [6], Ewertz M [3]).
Inclusion of intermediate levels of consumption:
Significant protective effects at any level of consumption were restricted to one cohort, including 96 cases at the level of consumption of ≥ 154 g/day
(31; McEligot AJ). No other (non)significant associations were found.
Conclusion: A significantly increased risk was found in one cohort, but no associations with breast cancer risk were found in the remaining cohorts.
Furthermore, no significant associations were found with breast cancer recurrence. No evidence was found for an association between total vegetables and either
breast cancer risk or breast cancer recurrence.
Protective associations against mortality were found in 4 cohorts, but these were mostly nonsignificant. The cohorts included 48% of all cases. Suggestive
evidence was found for a protective effect of total vegetables against breast cancer mortality (- 10%). No level of consumption could be defined for this effect.
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 38) George SM (2008) | The NIH-AARP Diet and Health Study | 5,815 | RR = 1.08 (1.00-1.18; P = 0.009) |
| 29) Hirvonen T (2006) | The SU.VI.MAX Study | 95 | No significant association (P = 0.98) |
| 24) Sonestedt E (2008) | The Malmö Diet and Cancer Cohort | 544 | HR = 0.84 (0.64-1.11; P = 0.18) |
| 22) Maynard M (2003) | The Boyd Orr cohort | 82 | OR = 1.43 (0.70-2.92; P = 0.59) |
| 21) van Gils CH (2005) | The EPIC Study | 3,659 | RR = 0.98 (0.84-1.14) |
| 20) Iwasaki M (2008) | The JPHC Study | 144 | No significant association (P = 0.20) |
| 15) Smith-Warner SA (2001) | Pooled analysis of 8 cohort studies | 7,377 | RR = 0.96 (0.89-1.04; P = 0.54) |
| 11) Jarvinen R (1997) | The Finnish Mobile Clinic Health Study | 88 | No significant association (no data shown) |
| 1) Shibata A (1992) | The Leisure World Study | 219 | RR = 0.96 (0.69-1.34) |
| Total number of cases: 18,023 | Average RR = 1.00 |
| Author | Cohort name | Cases | End point | Relative Risk (RR) | Dietary assessment following cancer diagnosis |
|---|---|---|---|---|---|
| 35) Pierce JP (2007) | The WHEL Trial | 517 | Breast cancer events | HR = 0.97 (0.67-1.40) | yes |
| 12) Hebert JR (1998) | No cohort name defined | 109 | Breast cancer recurrence | RR = 0.46 (P = 0.08) among postmenopausal women | Yes |
| Total number of cases: 626 | Average RR = 0.88 |
| Author | Cohort name | Cases | Relative Risk (RR) | Dietary assessment following cancer diagnosis |
|---|---|---|---|---|
| 35) Pierce JP (2007) | The WHEL Trial | 314 | HR = 1.19 (0.74-1.90) | Yes |
| 32) Fink BN (2006) | The Long Island Breast Cancer Study Project | Premenopausal: 43. Postmenopausal: 131. | Premenopausal: HR = 1.40 (0.71-2.76; P = 0.53). Postmenopausal: HR = 0.92 (0.57-1.48; P = 0.52) | Yes |
| 31) McEligot AJ (2006) | No cohort name defined | 96 | HR = 0.57 (0.35-0.94; P = 0.02) | Yes |
| 23) Goodwin PJ (2003) | No cohort name defined | 52 | No significant effect (no data shown) | Yes |
| 22) Maynard M (2003) | The Boyd Orr Cohort | 36 | OR = 0.86 (0.30-2.47; P = 0.35) | No |
| 12) Hebert JR (1998) | No cohort name defined | 73 | RR = 0.31 (P = 0.08) among postmenopausal women | Yes |
| 6) Ingram D (1994) | No cohort name defined | 21 | No significant associaton (P = 0.94) | Yes |
| 4) Holmes D (1999) | The Nurses' Health Study | 378 | RR = 0.81 (0.59-1.11; P = 0.07) | Yes |
| 3) Ewertz M (1991) | No cohort name defined | Not defined | A nonsignificant slightly decreased risk (no data shown) | Yes |
| Total number of cases: 1,144 + X | Average RR = 0.90 |
| Author | Cohort name | Subjects | Years of follow-up | Cases | End point | Consumption of | Relative Risk (RR) | Adjustments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 38) George SM (2008) | The National Institutes of Health-AARP Diet and Health Study. | 195,229 women aged 50-71. (USA) | 1995-2003 | 5,815 | Breast cancer incidence | Vegetables (excluding potatoes) |
RR = 1.08 (1.00-1.18; P = 0.009) for the highest vs lowest quintile of consumption. Amount specific data (range of intake [cup equivalents/1000 kcal]): 0-0.56: RR = 1. 0.56-0.79: RR = 0.98 (0.90-1.06). 0.79-1.04: RR = 1.01 (0.92-1.09). 1.04-1.43: RR = 1.04 (0.96-1.13). 1.43-4.38: RR = 1.08 (1.00-1.18). 1 cup = 237 mL. One cup is 1 cup of raw/cooked vegetable, 1 cup of 100% juice, or 2 cups of raw leafy greens. | Age, smoking, energy intake, BMI, alcohol, physical activity, education , race, marital status, family history, menopausal hormone therapy, and fruit intake. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 29) Hirvonen T. (2006) | the SUpplementation en VItamines et Mineraux AntioXydants study (SU.VI.MAX). | 4,396 women (aged 35-60) in a double-blind placebo-controlled primary-prevention trial undertaken to determine wether supplementation with antioxidant vitamins and minerals at nutritional doses can decrease the incidence of cancers and cardiovascular diseases. (France) | 6.6 (1994-2002) | 95? | breast cancer risk | Vegetables (not defined) | No significant difference was found between cases (174 g/d) and noncases (175 g/d) in their consumption of vegetables (P = 0.98). | None. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 24) Sonestedt E (2008) | The Malmö Diet and Cancer Cohort | 15,773 women age 46-75. (Sweden) | 10.3 (1991-96 to 2004) | 544 | Invasive breast cancer incidence (excluding in situ cases) | Vegetables (not defined) |
HR = 0.84 (0.64-1.11; P = 0.18) for the highest vs lowest quintile of consumption. Amount specific data (g/day): 82: HR = 1. 130: HR = 0.83 (0.63-1.08). 170: HR = 0.85 (0.65-1.11). 218: HR = 0.75 (0.57-0.99). 312: HR = 0.84 (0.64-1.11).
The risk estimates were essentially the same when restricting analyses to individuals .55 years at baseline (data not shown). Season of data collection, diet interviewer, method version, age, total energy, weight, height, educational status, smoking habits, leisure tiime physical activity, hours of household activities, alcohol consumption, age at menopause, parity and current use of MHT. |
24) Mattisson I. (2004) | The Malmö Diet And Cancer Cohort. | 11,726 postmenopausal women aged ≥ 50. | (Sweden) 7.6 | 342? | Breast cancer risk | (including in situ cases) Total vegetables (not defined) | No significant difference between cases (154 g/day), and controls (158 g/day). | Unadjusted? |
22) Maynard M. (2003) | The Boyd Orr Cohort. | 3.878 children -mean age 8 years- (1.959 women/1.919 men). (England/Scotland) | > 60 years (1937-39 to 2000) | 82? | breast cancer incidence | Vegetables (Not defined. Excluding potatoes) |
OR = 1.43 (0.70-2.92; P = 0.59) for the highest vs lowest quartile of consumption. | Amount specific data (mean intake in g/day): 23.1: OR = 1. 47.3: OR = 1.37 (0.72-2.63). 68.5: OR = 0.86 (0.42-1.76). 115.2: OR = 1.43 (0.70-2.92). Intra-family clustering. Age, sex, energy, food expenditure, Townsend score, season, and district. |
21) van Gils CH. (2005) | The EPIC Study. | 285 526 women between the ages of 25 and 70 years. | (8 European countries. Excluding Greece and Norway) 5.4 | (1992-98 to 2002) 3,659 | invasive breast cancer risk | Total vegetables (leafy vegetables, fruiting vegetables, root vegetables, cabbages, mushrooms, grain and pod vegetables, onion and garlic, stalk vegetables and sprouts, mixed salads and mixed vegetables, and unclassified. Excluding legumes and potatoes and other tubers) |
RR = 0.98 (0.84-1.14; P = 0.65) for the highest vs lowest quintile of consumption. | Amount specific data (g/d): ≤ 109: RR = 1. > 109-≤ 160: RR = 0.85 (0.74-0.97). > 160-≤ 221: RR = 0.96 (0.84-1.10). > 221-≤ 309: RR = 0.95 (0.83-1.10). > 309: RR = 0.98 (0.84-1.14). Women diagnosed at age 50 or younger: RR = 1.25 (0.86-1.82; No P-value). There was no interaction of BMI with total vegetables (P = 0.60). Stratified by country: No association was found in any country (P-values ≥ 28), except for a nonsignificantly increased risk in Spain: RR = 1.63 (0.96-2.77; P = 0.09. N = 205 cases. Table). Stratified by center and age. Adjusted for energy intake divided into energy from fat and energy from nonfat sources, alcohol intake, saturated fat intake, height, weight, age at menarche, parity, current oral contraceptive use, current use of hormone therapy, menopausal status, smoking status, physical activity, and education. |
21) Olsen A (2003) | The Diet, Cancer and Health Cohort | 23,798 postmenopausal women age 50-64. | (Denmark) 1993-97 to 2000 | 425 | (303 ER+, and 91 ER-) Breast cancer risk | Vegetables (leafy vegetables, fruiting vegetables, root vegetables other than potatoes cabbages, mushrooms, onion/garlic, stalk vegetables). Excluding potatoes and pulses) |
IRR = 0.98 (0.89-1.09) per 100 g daily intake. |
Age, time under study, parity, previous benign breast tumor surgery, education, use of hormone replacement therapy, duration of HRT use, intake of alcohol and BMI. |
20) Iwasaki M (2008) | The Japan Public Health Center-based Prospective Study (JPHC). | 24,226 women ages 40-69. | (Nested case-control) 10.6 | (1990-95 to 2002) 144 | Breast cancer incidence | Vegetables (not defined) | No significant difference in intake of cases (121.2 g/d) vs controls (115.9 g/d; P = 0.20). | Age and cohort. |
19) Smith-Warner SA (2001) | The Sweden Mammography Cohort | 61,471 women aged 40-76. | 1987-1997 | 1,318? | Breast cancer risk | Total vegetables (Vegetables and vegetable juice. Excluding potatoes and mature beans | RR = 1.01 (0.93-1.11) for an increment of 100 g/d. | Age at menarche, interaction between parity and age at first child, oral contraceptive use, history of benign breast disease, menopausal status at follow-up, postmenopausal hormone use, family history of breast cancer, smoking status, education, BMI, BMI-menopausal status interaction, height, alcohol intake, and energy intake. |
18) Smith-Warner SA (2001) | The New York University Women's Health Study | 14,006 women aged 34-65. | 1985-1994 | 385? | Breast cancer risk | Total vegetables (Vegetables and vegetable juice. Excluding potatoes and mature beans | RR = 0.97 (0.90-1.04) for an increment of 100 g/d. | Age at menarche, interaction between parity and age at first child, oral contraceptive use, history of benign breast disease, menopausal status at follow-up, postmenopausal hormone use, family history of breast cancer, smoking status, education, BMI, BMI-menopausal status interaction, height, alcohol intake, and energy intake. |
17) Smith-Warner SA (2001) | The New York State Cohort | 18,475 women aged 50-93. | 1980-1987 | 367? | Breast cancer risk | Total vegetables (Vegetables and vegetable juice. Excluding potatoes and mature beans | RR = 1.04 (0.93-1.15) for an increment of 100 g/d. | Age at menarche, interaction between parity and age at first child, oral contraceptive use, history of benign breast disease, menopausal status at follow-up, postmenopausal hormone use, family history of breast cancer, smoking status, education, BMI, BMI-menopausal status interaction, height, alcohol intake, and energy intake. |
16) Smith-Warner SA (2001) | The Adventist Health Study | 15,172 women aged 28-90. | 1976-1982 | 160? | Breast cancer risk | Total vegetables (Vegetables and vegetable juice. Excluding potatoes and mature beans) | RR = 1.10 (0.88-1.38) for an increment of 100 g/d. | Age at menarche, interaction between parity and age at first child, oral contraceptive use, history of benign breast disease, menopausal status at follow-up, postmenopausal hormone use, family history of breast cancer, smoking status, education, BMI, BMI-menopausal status interaction, height, alcohol intake, and energy intake. |
15) Smith-Warner SA. (2001) | Pooled Analysis of 8 Cohort Studies. | 351,825 | 5-16 | 7,377? | (1,052 premenopausal, and 5,447 postmenopausal) Invasive breast cancer risk | Total vegetables (Vegetables and vegetable juice. Excluding potatoes and mature beans. 5-33 items across studies.) |
INCLUSION CRITERIA: |
RELATIVE RISK:
Age at menarche, interaction between parity and age at birth of first child, oral contraceptive use (ever/never), history of benign breast disease, menopausal status at follow-up, postmenopausal hormone use, family history of breast cancer, smoking status (ever/never), education, BMI, BMI-menopausal status interaction, height, alcohol intake, and energy intake. |
Simultaneous adjustment for total fruit and total vegetable intakes on a continuous scale (results not shown) did not materially alter the results observed when each group was included in a separate model. 11) Jarvinen R. (1997) | The Finnish Mobile Clinic Health Cohort | 4.697 aged ≥ 15. | up to 25 | (1967-72 to 1991) 88? | Breast cancer risk | Vegetables (not defined) | No significant association (No data shown). | Age, BMI, parity, region, occupation, and smoking. |
10) Smith-Warner SA (2001) | The Iowa Women's Health Study | 34,406 women aged 55-69. | 1986-1995 | 1,130? | Breast cancer risk | Total vegetables (Vegetables and vegetable juice. Excluding potatoes and mature beans | RR = 0.98 (0.93-1.03) for an increment of 100 g/d. | Age at menarche, interaction between parity and age at first child, oral contraceptive use, history of benign breast disease, menopausal status at follow-up, postmenopausal hormone use, family history of breast cancer, smoking status, education, BMI, BMI-menopausal status interaction, height, alcohol intake, and energy intake. |
7) Smith-Warner SA (2001) | The Netherlands Cohort Study | 62,412 women aged 55-69. | 1986-1992 | 937? | Breast cancer risk | Total vegetables (Vegetables and vegetable juice. Excluding potatoes and mature beans | RR = 0.90 (0.81-1.00) for an increment of 100 g/d. | Age at menarche, interaction between parity and age at first child, oral contraceptive use, history of benign breast disease, menopausal status at follow-up, postmenopausal hormone use, family history of breast cancer, smoking status, education, BMI, BMI-menopausal status interaction, height, alcohol intake, and energy intake. |
7) Verhoeven DT (1997) | The Netherlands Cohort Study | 62,573 women aged 55-69. | 4.3 | (1986-1990) 519 | Breast cancer incidence | Vegetables (not defined) |
RR = 0.94 (0.67-1.31; P = 0.30) for the highest vs lowest quintile of consumption. | Amount specific data (g/day): 108.0: RR = 1. 148.0: RR = 1.04 (0.75-1.43). 183.0: RR = 0.89 (0.65-1.24). 224.0: RR = 0.85 (0.61-1.19). 303.0: RR = 0.94 (0.67-1.31). Age, energy, alcohol, history of benign breast disease, maternal breast cancer, breast cancer in sister, age at menarche, age at menopause, age at first birth, parity. |
5) Smith-Warner SA (2001) | The Canadian National Breast Screening Study | 56,837 women aged 40-59. | 1982-1987 | 419? | Breast cancer risk | Total vegetables (Vegetables and vegetable juice. Excluding potatoes and mature beans | RR = 0.98 (0.89-1.07) for an increment of 100 g/d. | Age at menarche, interaction between parity and age at first child, oral contraceptive use, history of benign breast disease, menopausal status at follow-up, postmenopausal hormone use, family history of breast cancer, smoking status, education, BMI, BMI-menopausal status interaction, height, alcohol intake, and energy intake. |
5) Rohan TE. (1993) | The Canadian National Breast Screening Study. | 56,837 women. | (Nested case-control study) 1982-1987 | 518 | Breast cancer risk | Vegetables (not defined) |
OR = 0.86 (0.61-1.23; P = 0.752) for the highest vs lowest quintile of consumption. | Amount specific data (g/day): < 203: OR = 1. 203-269: OR = 0.81 (0.57-1.15). 269-373: OR = 1.05 (0.75-1.47). 373-433: OR = 0.97 (0.69-1.37). > 433: OR = 0.86 (0.61-1.23). Age, age at menarche, surgical menopause, age at first livebirth, years of education, family history of breast cancer, history of benign breast disease, and other contributors to total food intake. |
4) Fung TT. (2005) | The Nurses' Health Study. | 71,058 postmenopausal women. | (USA) 1984-2000 | 512? | estrogen receptor negative (ER-) breast cancer risk | Vegetables (not clearly defined) |
RR = 0.56 (0.39-0.81) for the highest vs lowest quartile of consumption. | Amount specific data (servings): 2-3/week: RR = 1. 1-1.9/day: RR = 0.70 (0.49-1.00). 2-3.9/day: RR = 0.73 (0.52-1.03). ≥ 4/day: RR = 0.56 (0.39-0.81). age, smoking status (never, past, current + amount), BMI, multivitamin, energy, physical activity in METs, family history of breast cancer, history of benign breast disease, duration of menopause, age at menopause, age at menopause and use of hormone replacement therapy, age at menarche, parity and age at first birth, BMI at age 18, weight change since age 18, adult height and alcohol intake. |
4) Smith-Warner SA (2001) | The Nurses' Health Study | 89,046 women aged 34-59. | Part A: 1980-1986. | Part B: 1986-1996. Part A: 1,023? | Part B: 1,638? Breast cancer risk | Total vegetables (Vegetables and vegetable juice. Excluding potatoes and mature beans |
|
Age at menarche, interaction between parity and age at first child, oral contraceptive use, history of benign breast disease, menopausal status at follow-up, postmenopausal hormone use, family history of breast cancer, smoking status, education, BMI, BMI-menopausal status interaction, height, alcohol intake, and energy intake. |
4) Zhang S. (1999) | The Nurses' Health Study. | 83,234 women aged 33-60. | (USA) 14 | (1980-1994) 2,697? | (784 premenopausal, 1,913 postmenopausal) Invasive breast cancer incidence | Vegetables (not defined) |
|
Age, length of follow-up, total energy, parity, age at first birth, age at menarche, history of breast cancer in mother or sister, history of benign breast disease, alcohol intake, BMI at age 18, weight change from age 18 y, and height. |
Additionally for postmenopausal women: age at menopause, and postmenopausal hormone use. 4) Hunter DJ. (1993) | The Nurses' Health Study. | 89,494 women aged 34-59. | (USA) 8 | (1980-1988) 1,439? | Breast cancer risk | Vegetables (not defined) |
RR = 0.83 (0.66-1.03; P = 0.04) for the highest vs lowest quintile of consumption. | Amount specific data (servings/day): < 0.9: RR = 1. 0.9-1.2: RR = 0.79 (0.62-0.99). 1.3-1.6: RR = 0.81 (0.64-1.01). 1-7-2.1: RR = 0.72 (0.57-0.91). ≥ 2.2: RR = 0.83 (0.66-1.03). Age, lenght of follow-up, energy intake, parity, age at first birth, age at menarche, history of breast cancer, menopausal status, BMI, alcohol intake, and a history of benign breast disease. |
1) Shibata A. (1992) | The Leisure World Study. | 11,580 residents of a retirement community. | (USA) 1981-1989 | 219 | Breast cancer risk | Vegetables (Leafy green lettuce [Romaine, Boston, bibb, butterhead, endive, escarole, salad bowl, red leafy lettuce], other leafy greens [spinach, chard, beet greens, turnip greens, mustard greens, collards, kale, dandelion greens], iceberg or head lettuce, cabbage [incude sauerkraut and coleslaw], white potatoes or turnips, sweet potatoes, yams, pumpkin [including in pie or soup], carrots, winter squash [butternut, hubbard, acorn squash [including in pie or soup], summer squash [zucchini, yellow crookneck, yellow straightneck, cocozelle, scallop squash, broccoli, tomatoes [fresh or cooked, including tomatoes in a sauce such as spaghetti or tomato soup], green peas [including snow peas and Chines pea pods], green beans or string beans, lima beans or blackeye beans, corn, asparagus, sweet green peppers, sweet red peppers, hot red chili peppers [including hot pepper sauce, chili powder, cayenne pepper, tobasco sauce, Brussels sprouts, cauliflower) |
RR = 0.96 (0.69-1.34; No P-value) for the highest vs lowest tertile of consumption. | Amount specific data (servings/day): < 3.2: RR = 1. 3.2-< 4.8: RR = 1.14 (0.83-1.57). ≥ 4.8: RR = 0.96 (0.69-1.34). Age and smoking. |
Adjustment for BMI or physical activity did not materially alter the results (data not shown).
|