Grapefruit and breast cancer.

Breast cancer risk: Data about the relation with breast cancer risk was provided by 3 cohorts. A significantly increased risk was found in one cohort (33), but no associations were found in the other cohorts (4, 21).
Effect modification: Significant differences in effect between cohorts were found among never never users of hormone therapy.

Breast cancer mortality: No data was found.

Conclusion: Effects were restricted to findings from one cohort. No evidence was found for an association between grapefruit and breast cancer.

Author

Cohort name

Subjects

Years of follow-up

Cases

End point

Consumption of

Relative Risk (RR)

Adjustments

33) Monroe KR. (2007)

The Multiethnic Cohort Study.

46,080 postmenopausal women aged 45-75 from five racial/ethnic groups (USA)

1993-96 to 2002

1,657

Breast cancer incidence

Grapefruit or pomelo

RR = 1.30 (1.06-1.58; P = 0.015) for the highest vs lowest quartile of consumption.

Amount specific data (g per day):
None: RR = 1.
> 0 to < 30: RR = 1.08 (0.97-1.20).
≥ 30 to < 60: RR = 1.07 (0.86-1.34).
≥ 60: RR = 1.30 (1.06-1.58).

**Stratified by BMI:**
BMI < 25.0 (875 cases)	BMI ≥ 25 (782 cases)
RR = 1.32 (1.02-1.72; P = 0.011) for the highest vs lowest quartile of consumption. Amount specific data (g per day): None: RR = 1. > 0 to < 30: RR = 1.05 (0.90-1.22). ≥ 30 to < 60: RR = 1.14 (0.85-1.52). ≥ 60: RR = 1.32 (1.02-1.72).	RR = 1.46 (1.10-1.96; P = 0.113) for the highest vs lowest quartile of consumption. Amount specific data (g per day): None: RR = 1.16 (1.00-1.34) > 0 to < 30: RR = 1.30 (1.11-1.52). ≥ 30 to < 60: RR = 1.16 (0.83-1.62). ≥ 60: RR = 1.46 (1.10-1.96).

**Stratified by hormone therapy:**
Never hormone therapy (631 cases)	Past hormone therapy (259 cases)	Current oestrogen therapy (275 cases)	Current oestrogen + progestin therapy (492 cases)
RR = 1.44 (1.08-1.93; P = 0.038) for the highest vs lowest quartile of consumption. Amount specific data (g per day): None: RR = 1 (= reference group). > 0 to < 30: RR = 1.19 (1.00-1.41). ≥ 30 to < 60: RR = 0.87 (0.59-1.27). ≥ 60: RR = 1.44 (1.08-1.93).	RR = 1.17 (0.72-1.92; P = 0.97) for the highest vs lowest quartile of consumption. Amount specific data (g per day): None: RR = 1.22 (0.99-1.50). > 0 to < 30: RR = 1.13 (0.88-1.43). ≥ 30 to < 60: RR = 1.44 (0.87-2.37). ≥ 60: RR = 1.17 (0.72-1.92).	RR = 2.12 (1.29-3.49; P = 0.22) for the highest vs lowest quartile of consumption. Amount specific data (g per day): None: RR = 1.56 (1.21-2.01). > 0 to < 30: RR = 1.70 (1.29-2.23). ≥ 30 to < 60: RR = 1.85 (1.06-3.25). ≥ 60: RR = 2.12 (1.29-3.49).	RR = 2.55 (1.80-3.63; P = 0.13) for the highest vs lowest quartile of consumption. Amount specific data (g per day): None: RR = 2.01 (1.69-2.40). > 0 to < 30: RR = 2.09 (1.73-2.51). ≥ 30 to < 60: RR = 2.48 (1.72-3.58). ≥ 60: RR = 2.55 (1.80-3.63).

One grapefruit was estimated to be 240 g.

Stratified on age at recruitment, year of recruitment, race/ethnicity, and study centre. Adjusted for weight, height, physical activity, age at menarche, age at first birth, parity, age at and type of menopause, oestrogen and/or progestin use, smoking, education, family history of breast cancer, alcohol, total energy, saturated fat, dietary fibre, and soluble fibre.

21) Spencer EA (2009)

The EPIC Study

114,504 women from 3 European countries (Denmark, France, and the UK).

9.5
(1993-2000 to 2006)

3,747

Breast cancer incidence

Grapefruit

HR = 0.93 (0.77-1.13; P = 0.5) for the highest vs lowest quintile of consumption.

Amount specific data (g/day):
0: HR = 1.
1-< 10: HR = 0.94 (0.86-1.04).
10-< 30: HR = 1.02 (0.94-1.12).
30-< 60: HR = 0.99 (0.88-1.11).
≥ 60: HR = 0.93 (0.77-1.13).

No significant association between grapefruit intake and breast cancer risk was found for women recruited in Denmark (P = 0.7), France (P = 0.7), or the UK (P = 0.4).

**Stratified by menopausal status:**
Postmenopausal women (1,570 cases)	Premenopausal women (1,018 cases)
HR = 0.97 (0.75-1.27; P = 0.6) for the highest vs lowest quintile of consumption. Amount specific data (g/day): 0: HR = 1. 1-< 10: HR = 0.92 (0.80-1.07). 10-< 30: HR = 1.16 (1.00-1.35). 30-< 60: HR = 0.95 (0.78-1.14). ≥ 60: HR = 0.97 (0.75-1.27).	HR = 1.19 (0.81-1.75; P = 0.2) for the highest vs lowest quintile of consumption. Amount specific data (g/day): 0: HR = 1. 1-< 10: HR = 1.01 (0.85-1.20). 10-< 30: HR = 1.05 (0.89-1.24). 30-< 60: HR = 1.15 (0.92-1.43). ≥ 60: HR = 1.19 (0.81-1.75).

Postmenopausal women.
Stratified by HRT use:
Never-users (772 cases)	Former users (290 cases)	Current users (508 cases)
HR = 1.20 (0.85-1.68; P = 0.8) for the highest vs lowest quintile of consumption. Amount specific data (g/day): 0: HR = 1. 1-< 10: HR = 0.95 (0.77-1.17). 10-< 30: HR = 1.25 (1.02-1.53). 30-< 60: HR = 0.87 (0.66-1.14). ≥ 60: HR = 1.20 (0.85-1.68).	HR = 0.63 (0.31-1.29; P = 0.4) for the highest vs lowest quintile of consumption. Amount specific data (g/day): 0: HR = 1. 1-< 10: HR = 0.79 (0.56-1.12). 10-< 30: HR = 1.01 (0.71-1.43). 30-< 60: HR = 0.91 (0.59-1.39). ≥ 60: HR = 0.63 (0.31-1.29).	HR = 0.81 (0.48-1.37; P = 0.7) for the highest vs lowest quintile of consumption. Amount specific data (g/day): 0: HR = 1. 1-< 10: HR = 0.96 (0.74-1.24). 10-< 30: HR = 1.12 (0.86-1.47). 30-< 60: HR = 1.12 (0.81-1.55). ≥ 60: HR = 0.81 (0.48-1.37).

Age as the underlying time variable, stratified by center, number of full-term pregnancies, age at first birth, menopausal status/age at menopause, and use of hormones, and adjusted for age at menarche, BMI, energy intake, and alcohol intake.

4) Kim EH (2008)

The Nurses' Health Study.

77,050 women aged 38-63 (of whom 73,411 postmenopausal).

1984-2002

4315 (of whom 3570 postmenopausal)

Breast cancer incidence

Grapefruit


All women:	Postmenopausal women only:
RR = 1.00 (0.86-1.15; P = 0.5) for the highest vs lowest quartile of consumption. Amount specific data (grapefruits/day): 0: RR = 1. > 0-1/8: RR = 1.02 (0.94-1.10). ≥1/8-1/4: RR = 0.96 (0.86-1.07). ≥1/4: RR = 1.00 (0.86-1.15).	RR = 0.97 (0.83-1.14; P = 0.34) for the highest vs lowest quartile of consumption. Amount specific data (grapefruits/day): 0: RR = 1. > 0-1/8: RR = 1.03 (0.95-1.12). ≥1/8-1/4: RR = 0.97 (0.86-1.09). ≥1/4: RR = 0.97 (0.83-1.14).

Results did not change after inclusion of alcohol, saturated fat, dietary fiber, and soluble fibre in the models.

Stratified analyses:
-Stratification by BMI did not alter the risk.
-Stratification by hormone therapy showed a significant decrease in risk of breast cancer with greater intake of grapefruit in women who never used hormone therapy (RR = 0.78; 95% CI = 0.59-1.04; P = 0.03 for comparing ≥1/4 grapefruit day to none).
-The association differed significantly by oestrogen and progesterone receptor status of the tumours. No association was observed in women with oestrogen and progesterone receptor positive cancers. However, in women with oestrogen and progesterone receptor negative cancers, there was a significant decrease in breast cancer risk with increased consumption of grapefruit (RR = 0.60; 95% CI = 0.37-0.98; P = 0.03 for consumption ≥1/4 grapefruit/day to none).

Energy, age, time period, height, parity, age at first birth, weight change since age 18 years, BMI at age 18 years, age at menopause, use of hormone replacement therapy, family history of breast cancer, benign, breast disease, age at menarche and physical activity.

Cancer & Diet. A systematic review.

Literature review.

Relating various aspects of our diet
to breast cancer risk & mortality.

Grapefruit and breast cancer.

Cancer & Diet. A systematic review.

Literature review.

Relating various aspects of our dietto breast cancer risk & mortality.

Grapefruit and breast cancer.

Relating various aspects of our diet
to breast cancer risk & mortality.