Fruit and breast cancer.
Total breast cancer risk: Data about total fruit in relation to total breast cancer risk was provided by a pooled analysis of 8 cohorts, and 9 additional
cohorts, including a total of 18,425 cases.
A weak significant protective effect was found in one cohort of very large size, including 5,815 cases (38). And a weak nonsignificant protective
effect was found in the pooled analysis, including 7,377 cases (15). No other (non)significant associations were found. The average RR = 0.96 (excluding
incomplete data from Hirvonen T [30], Iwasaki M [20], Jarvinen R [11]).
No levels of consumption were defined in the pooled analysis, but effects were restricted to above median consumption (quartiles 3-4).
Inclusion of intermediate levels of consumption:
(Non)significant effects at any level of consumption were as follows:
- Shibata A (1) Significant protective at 192-< 296 g/day.
- George SM (38) Though the trend was significant, the effect was nonsignificantly protective at > 608 g/day.
Effect modification: Effect modification was found in the pooled analysis of 8 cohorts (Smith-Warner SA). Protective effects against cancer risk
were restricted to never users of oral contraceptives.
Disease progression: Data about total fruit in relation to disease progression was provided by 2 cohorts, including a total of 545 cases.
No (non)significant associations were found with breast cancer recurrence. The average RR = 0.82.
Breast cancer mortality: Results were included about a) breast cancer mortality, and b) mortality following diagnosis of breast cancer. If data about
both all-cause mortality, and breast cancer-specific mortality were available following diagnosis of breast cancer, total mortality was chosen as end point.
Data about total fruit in relation to breast cancer death was provided by 10 cohorts, including a total of 1,264 cases.
A significant protective effect was found in one cohort (6), and a nonsignificant protective effect was found in one other cohort (31), including
a total of 117 cases for both cohorts combined. No other (non)significant associations were found. The average RR = 0.90 (excluding incomplete data from Goodwin PJ [23],
Ingram D [6]).
Inclusion of intermediate levels of consumption:
Significant effects at any level of consumption were restricted to one cohort. A significantly increased risk was found at the level of consumption of 235-350 g/d
(Pierce JP). Though trends were protective in 2 cohorts, no (non)significant protective effects were found in any cohort.
Conclusion: A weak significant protective effect of total fruit against breast cancer risk was found in one cohort of very large size, and a
weak nonsignificant protective effect was found in a pooled analysis of 8 cohorts. The combined amount of cases from these cohorts included 72% of all cases.
Suggestive evidence was found for a weak protective effect of total fruit against breast cancer risk (- 4%). This effect may be restricted to never users of oral contraceptives.
No level of consumption could be defined for this effect, but above median consumption seems required.
Protective effects against mortality were found in 2 cohorts, and these were significant once. These cohorts included 9% of all cases. No associations were
found with breast cancer recurrence. No evidence was found for an association between total fruit and breast cancer recurrence or breast cancer mortality.
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 38) George SM (2008) | The NIH-AARP Diet and Health Study | 5,815 | RR = 0.91 (0.84-1.00; P = 0.01) |
| 30) Hirvonen T (2006) | The SU.VI.MAX Study | 95 | No significant association (P = 0.73) |
| 24) Sonestedt E (2008) | The Malmö Diet and Cancer Cohort | 544 | HR = 0.93 (0.70-1.23; P = 0.58) |
| 22) Maynard M (2003) | The Boyd Orr Cohort | 82 | OR = 1.08 (0.52-2.25; P = 0.61) |
| 21) van Gils CH (2005) | The EPIC Study | 3,659 | RR = 1.09 (0.94-1.25; P = 0.11) |
| 20) Iwasaki M (2008) | The JPHC Study | 144 | No significant association (P = 0.79) |
| 15) Smith-Warner SA (2001) | Pooled analysis of 8 cohort studies | 7,377 | RR = 0.93 (0.86-1.00; P = 0.08) |
| 13) Key TJ (1999) | The Hiroshima/Nagasaki Life Span Study | 402 | RR = 0.95 (0.71-1.27; P = 0.53) |
| 11) Jarvinen R (1997) | The Finnish Mobile Clinic Health Cohort | 88 | No significant association (no data shown) |
| 1) Shibata A (1992) | The Leisure World Study | 219 | RR = 0.82 (0.60-1.12) |
| Total number of cases: 18,425 | Average RR = 0.96 |
| 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 = 0.81 (0.57-1.16) | Yes |
| 14) Saxe GA (1999) | No cohort name defined | 28 | Breast cancer recurrence | HR = 0.96 (0.63-1.45) | Yes |
| Total number of cases: 545 | Average RR = 0.82 |
| Author | Cohort name | Cases | Relative Risk (RR) | Dietary assessment following cancer diagnosis |
|---|---|---|---|---|
| 35) Pierce JP (2007) | The WHEL Trial | 314 | HR = 0.76 (0.48-1.19) | Yes |
| 32) Fink BN (2006) | The Long Cancer Island Breast Cancer Study Project | Premenopausal: 43. Posmenopausal: 132. | Premenopausal: HR = 1.10 (0.48-2.52; P = 0.28). Postmenopausal: HR = 0.87 (0.57-1.35; P = 0.34) | Yes |
| 31) McEligot AJ (2006) | No cohort name defined | 96 | HR = 0.63 (0.38-1.05; P = 0.08) | Yes |
| 23) Goodwin PJ (2003) | No cohort name defined | 52 | No significant association (no data shown) | Yes |
| 22) Maynard M (2003) | The Boyd Orr Cohort | 36 | OR = 1.25 (0.40-3.92; P = 0.73) | No |
| 14) Saxe GA (1999) | No cohort name defined | 26 | HR = 1.06 (0.69-1.63) | Yes |
| 13) Sauvaget C (2003) | The Hiroshima/Nagasaki Life Span Study | 76 | RR = 0.91 (0.48-1.72; P = 0.70) | No |
| 8) Appleby PN (2002) | The Health Food Shoppers Study | 90 | RR = 0.66 (0.38-1.14) | No |
| 6) Ingram D (1994) | No cohort name defined | 21 | A significant protective effect (P = 0.01) | Yes |
| 4) Holmes MD (1999) | The Nurses' Health Study | 378 | RR = 1.07 (0.77-1.49; P = 0.40) | Yes |
| Total number of cases: 1,264 | 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 | Fruit |
RR = 0.91 (0.84-1.00; P = 0.010) for the highest vs lowest quintile of consumption. Amount specific data (range of intake [cup equivalents/1000 kcal]): 0-0.60: RR = 1. 0.60-0.97: RR = 1.02 (0.94-1.11). 0.97-1.35: RR = 0.99 (0.91-1.07). 1.35-1.90: RR = 0.96 (0.88-1.04). 1.90-5.58: RR = 0.91 (0.84-1.00). 1 cup = 237 mL. One cup is 1 cup of raw/cooked fruit, 1 cup of 100% juice, or 0.5 cup of dried fruit. | Age, smoking, energy intake, BMI, alcohol, physical activity, education , race, marital status, family history, menopausal hormone therapy, and vegetable intake. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 30) 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 | Fruits (not defined) | No significant difference was found between cases (212 g/d) and noncases (210 g/d) in their consumption of fruits (P = 0.73). | 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) | Fruits and berries (not defined) |
HR = 0.93 (0.70-1.23; P = 0.58) for the highest vs lowest quintile of consumption. Amount specific data (g/day): 70: HR = 1. 134: HR = 1.06 (0.81-1.39). 189: HR = 0.82 (0.61-1.09). 254: HR = 1.03 (0.79-1.35). 364: HR = 0.93 (0.70-1.23).
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 fruit (including berries) (not defined) | No significant difference between cases (197 g/day), and controls (196 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 | Fruit (not defined) |
OR = 1.08 (0.52-2.25; P = 0.61) for the highest vs lowest quartile of consumption. | Amount specific data (mean intake in g/day): 0.6: OR = 1. 12.7: OR = 0.66 (0.33-1.34). 31.3: OR = 1.10 (0.58-2.10). 88.4: OR = 1.08 (0.52-2.25). 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 fruits (Mainly fresh fruits [90%], but included dried and canned fruits. Excluding juices) |
RR = 1.09 (0.94-1.25; P = 0.11) for the highest vs lowest quintile of consumption. | Amount specific data (g/d): ≤ 114: RR = 1. > 114-≤ 184: RR = 1.02 (0.89-1.17). > 184-≤ 260: RR = 1.00 (0.87-1.15). > 260-≤ 367: RR = 1.11 (0.97-1.27). > 367: RR = 1.09 (0.94-1.25). Women diagnosed at age 50 or younger: RR = 1.17 (0.84-1.64; No P-value). There was no interaction of BMI with total fruits (P = 0.58). Stratified by country: No association was found in any country (P-values ≥ 26), except for a nonsignificantly increased risk in Spain: RR = 1.75 (1.01-3.03; P = 0.06. 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) 4.7 | (1993-97 to 2000) 425 | (303 ER+, and 91 ER-) Breast cancer risk | Fruits (citrus fruits, apples, pears, bananas, peaches, strawberries, kiwi fruits, water melon, other melons, fruit porridge, preserved fruit) |
IRR = 1.05 (0.98-1.11) 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 | Fruit (not defined) | No significant difference in intake of cases (104.8 g/d) vs controls (99.4 g/d; P = 0.79). | 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 fruits (Fruits and fruit juice), and | Fruits without juice
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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 fruits (Fruits and fruit juice), and | Fruits without juice
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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 fruits (Fruits and fruit juice), and | Fruits without juice
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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 fruits (Fruits and fruit juice), and | Fruits without juice
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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 fruits (Fruits and fruit juice. 4-21 items across studies.), | and Fruits without juice
INCLUSION CRITERIA: |
RELATIVE RISK: TOTAL FRUITS:
Stratified by height: The RR for a 100-g/d increment of total fruit consumption was 1.01 (95% CI, 0.99-1.04) for women with heights less than 160 cm and 0.96 (95% CI, 0.88-1.04) for women with heights of 175 cm or more; however, the relationship was not monotonic across the 5 height categories (P for interaction = .01). FRUITS WITHOUT JUICE:
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. 13) Key TJ (1999) | The Hiroshima/Nagasaki Life Span Study. | 34,759 women. | (Japan) 1969-70 and/or 1979-81 to 1993 | 402 | Breast cancer incidence | Fruit (not defined) |
RR = 0.95 (0.71-1.27; P = 0.531) for the highest vs lowest tertile of consumption. | Amount specific data (Frequency of consumption): ≤ 1/week: RR = 1. 2-4/week: RR = 1.07 (0.78-1.46). ≥ 5/week: RR = 0.95 (0.71-1.27). Age, calendar period, city, age at time of bombing and radiation dose. |
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 | Fruits and berries (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 fruits (Fruits and fruit juice), and | Fruits without juice
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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 fruits (Fruits and fruit juice), and | Fruits without juice
|
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 | Fruit (not defined) |
RR = 0.76 (0.54-1.08; P = 0.10) for the highest vs lowest quintile of consumption. | Amount specific data (g/day): 64.9: RR = 1. 124.0: RR = 0.88 (065-1.19). 177.0: RR = 0.77 (0.55-1.06). 237.0: RR = 0.90 (0.66-1.22). 343.1: RR = 0.76 (0.54-1.08). 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 fruits (Fruits and fruit juice), and | Fruits without juice
|
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 | Fruit (not defined) |
OR = 0.81 (0.57-1.14; P = 0.174) for the highest vs lowest quintile of consumption. | Amount specific data (g/day): < 189: OR = 1. 189-282: OR = 0.84 (0.60-1.18). 282-373: OR = 1.01 (0.73-1.41). 373-491: OR = 0.76 (0.54-1.08). > 491: OR = 0.81 (0.57-1.14). 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 | Fruits (raisins, orange, grapefruit, prunes, banana, cantaloupe, water melon, apple, strawberry, blueberry, peach) |
RR = 0.74 (0.58-0.95) for the highest vs lowest tertile of consumption. | Amount specific data (servings): 2-3/week: RR = 1. 1-1.9/day: RR = 0.95 (0.77-1.16). ≥ 2/day: RR = 0.74 (0.58-0.95). 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 fruits (Fruits and fruit juice), and | Fruits without juice
|
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 | Fruits (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 | Fruit (not defined) | No apparent association. | 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 | Fruits (Cantaloupe, mangos, watermelon, apricots, nectarines [including apricot nectar], peaches, papayas, persimmons, sour cherries, prunes, prune juice, apples, applesauce [not apple juice], bananas, avocados, guacamole, pineapple, pineapple juice, blackberries, blueberries, raspberries, boysenberries, loganberries, sweet cherries, fruit cocktail, oranges, tangerines, mandarin oranges, orange juice, white grapefruit and juice, pink/red grapefruit and juice, honeydew, casaba melons, strawberries, cranberry juice cocktail, plums, rhubarb, grapes, pears, figs, raisins, dates) |
RR = 0.82 (0.60-1.12; No P-value) for the highest vs lowest tertile of consumption. | Amount specific data (servings/day): < 2.4: RR = 1. 2.4-< 3.7: RR = 0.71 (0.51-0.99). ≥ 3.7: RR = 0.82 (0.60-1.12). Age and smoking. |
Adjustment for BMI or physical activity did not materially alter the results (data not shown).
|