Abstract

OBJECTIVES:

• To review all prospective studies which provided data about total fruits or vegetables, their subgroups, and specific types of vegetables and fruits, in relationship with breast cancer risk, disease progression and mortality/survival.
• To define the amount of consumption found to be related with the described effects on cancer.
• To define possible effect modification by confounders.

DATA SOURCE: The Pubmed database was searched (No start date - Sep 11, 2009) for relevant articles using the keywords "cancer, neoplasm, or neoplasms" combined with "vegetables, vegetable, fruit, or fruits" and a fair amount of other keywords. The exact search term is described in the methods.
Prospective studies published in the English language were included. Reference lists were searched for additional articles.
RESULTS: 64 articles were found which provided information about 41 different cohorts.
Of these, 0 articles were excluded.
Results are described when any evidence for an association - as defined in the Methods - was found. In addition, data about total vegetables or fruits is described.

• Total disease risk.
  -Data about total vegetables was provided by a pooled analysis of 8 cohorts, and 8 additional cohorts, including a total of 18,023 cases. No evidence was found for an association between total vegetables and breast cancer risk.
  -Data about total fruit was provided by a pooled analysis of 8 cohorts, and 9 additional cohorts, including a total of 18,425 cases. Suggestive evidence was found for a protective effect of total fruit against breast cancer risk. This effect may be restricted to never users of oral contraceptives. No level of consumption could be defined for this effect.
  -Data about rosaceae was provided by a pooled analysis of 7 cohorts, including 7,217 cases. Items from the rosaceae family possibly protect against breast cancer risk.
• Advanced stage/metastatic disease risk or disease progression.
  -Data about total vegetables in relation to disease progression was provided by 2 cohorts, including a total of 626 cases. No evidence was found for an association between total vegetables and breast cancer recurrence.
  -Data about total fruit in relation to disease progression was provided by 2 cohorts, including a total of 545 cases. No evidence was found for an association between total fruit and breast cancer recurrence.
• Mortality risk.
  -Data about total vegetables in was provided by 9 cohorts, including a total of 1,144 cases. 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. No level of consumption could be defined for this effect.
  -Data about total fruit was provided by 10 cohorts, including a total of 1,264 cases. No evidence was found for an association between total fruit and breast cancer mortality.

CONCLUSION: Suggestive evidence was found for a protective effect of total fruit against breast cancer risk, which may be restricted to never users of oral contraceptives. And suggestive evidence was found for a protective effect of total vegetables against breast cancer mortality. No evidence was found for other associations with total vegetables or fruits.
Items from the rosaceae family possibly protect against breast cancer risk, but the effect is very weak, and none of the specific items in this family was associated with breast cancer. No other associations were found, and no level of consumption could be defined for any of the associations.

Total 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 significant trend of increased risk was found in one cohort of very large size, including 5,815 cases (38). No other (non)significant associations were found.

Inclusion of intermediate levels of consumption:
The figure below included RRs from all cohorts in which any (non)significant effect was found at any level of consumption. Significant protective effects were found in 3 cohorts. The level at which these effects could be found were mostly in the range of 1.5-3 servings/day (both 154-223 and ≥ 385; > 109-≤ 160; and 218 g/day for Zhang S, van Gils CH, and Sonestedt E, respectively).
Though the trend was significant, a nonsignificantly increased risk was found in one cohort of very large size at the level of consumption of ≥ 440 g/day (38; George SM).

Disease progression: Data about total vegetables in relation to disease progression was provided by 2 cohorts, including a total of 626 cases.
A nonsignificant trend of a protective effect against breast cancer recurrence among postmenopausal women was found in the smallest cohort (12), but no association was found in the larger cohort (35).

Breast cancer mortality: Results were included about a) breast cancer mortality, and b) 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 in one cohort [3]).
A significant protective effect was found in one cohort (31), and nonsignificant trends of a protective effect were found in 3 other cohorts (3, 4, 12), including a total of 547 + X cases for all 4 cohorts combined (> 48% of all cases). No other (non)significant associations were found.

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 significant trend of an 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. No level of consumption could be defined for this effect.

Total 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 trend of a protective effect was found in one cohort of very large size, including 5,815 cases (38). And a weak nonsignificant trend of a protective effect was found in the pooled analysis, including 7,377 cases (15). No other (non)significant associations were found.
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:
The figure below included RRs from all cohorts in which any (non)significant effect was found at any level of consumption. The level at which a significant protective effect could be found differed among the cohorts. A significant protective effect was found in one cohort of small size at the level of consumption of 192-< 296 g/d (Shibata A). Though the trend was significant, a nonsignificant protective effect was found in one cohort of very large size at the level of consumption of > 608 g/d (38; George SM)

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.

Breast cancer mortality: Results were included about a) breast cancer mortality, and b) 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 fruit in relation to breast cancer death was provided by 10 cohorts, including a total of 1,264 cases.
A significant trend of a protective effect was found in one cohort (6), and a nonsignificant trend of a 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.

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 protective trends were found in 2 cohorts, no (non)significant protective effects were found in any cohort.

Conclusion: A weak nonsignificant trend of a protective effect of total fruit against breast cancer risk was found in one cohort of very large size, and a weak nonsignificant trend of a 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 protective effect of total fruit against breast cancer risk. 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.
Trends of a protective effect against mortality were found in 2 cohorts, and these were significant once. The 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.