Dietary Intake of Isoflavone and All‐Cause Mortality in Women with Breast Cancer: the Breast Cancer Family Registry
Authors: Haslam Danielle Elizabeth , John Esther , Terry Mary Beth , Knight Julia , Andrulis Irene , Daly Mary , Buys Saundra , Zhang Fang Fang 
Published: November 2023

Background

Soy foods possess both anti‐estrogenic and estrogen‐like properties. Epidemiologic data on soy intake and breast cancer survival are sparse, especially from women living in North America who typically have a low intake.

Methods

We examined dietary intake of isoflavones, the major bioactive component of soy, in association with all‐cause mortality among 6,842 women diagnosed with a first primary invasive breast cancer that were enrolled in the Breast Cancer Family Registry and followed for a median length of 9.5 years. Dietary intake was assessed using a Food Frequency Questionnaire developed for the Multiethnic Cohort, with 5,178 women who reported pre‐diagnosis diet and 1,664 women who reported post‐diagnosis diet. Cox proportional hazard models were performed to estimate the hazard ratios (HR's) and 95% confidence intervals (CI's).

Results

We observed an overall 25% decrease in all‐cause mortality among women in the highest quartile of dietary isoflavone intake (≥1.4 mg/d) compared to those in the lowest quartile (<0.3 mg/d) (Q4 vs. Q1: HR = 0.75, 95% CI: 0.62 – 0.91, p trend=0.002). Reduced risk was observed only among post‐menopausal women (HR = 0.70, 95% CI: 0.52 – 0.93, p trend=0.01), women with a body mass index <25 kg/m2 (HR = 0.68, 95% CI: 0.51 – 0.90, p trend=0.01), women with negative tumor hormone receptors (HR=0.42, 95% CI: 0.22–0.80, p trend=0.006), and women who did not receive hormonal therapy (HR=0.68, 95% CI: 0.52–0.88, p trend=0.01). The inverse association was stronger for post‐diagnosis dietary intake of isoflavone (HR = 0.59, 95% CI: 0.39 – 0.90, p trend=0.01) than pre‐diagnosis intake (HR = 0.82, 95% CI: 0.66 – 1.02, p trend=0.06).

Conclusion

In this large ethnically‐diverse cohort of women with breast cancer, a higher dietary intake of isoflavones was associated with a reduced total mortality.

Characteristics of Women in the Breast Cancer Family Registry (BCFR) (N=6,842)

N (%) or Mean (SD)

Age at enrollment, y, mean (SD)
52.5 (22.5)

Race/ethnicity, N (%)

Non‐Hispanic White
4,068 (69.4)

Hispanic
1,112 (16.2)

Black
809 (11.8)

Asian/Pacific Islander
738 (10.8)

Other
118 (1.72)

Education, N(%)

High school or less
2,520 (36.8)

Some college or bachelor's degree
3,244 (47.4)

Graduate degree
1,045 (15.3)

Menopausal status at enrollemnt, N (%)

Pre‐menopausal
3,943 (57.6)

Post‐menopausal
2,902 (42.4)

Body Mass Index (BMI) at enrollment, kg/m2, mean (SD)
26.5 (5.90)

BMI status1, N (%)

Underweight
156 (2.28)

Normal Weight
3,139 (45.9)

Overweight
1,868 (27.3)

Obese
1,479 (21.6)

Recreational Physical Activity2, N (%)

Active
2,954 (43.2)

Inactive
3,609 (52.7)

Cigarette Smoking, N (%)

Never
3,967 (58.0)

Ever
2,864 (41.8)

Pack‐years (among smokers), mean (SD)
17.4 (18.3)

Lifetime Alcohol Consumption, N (%)

Nondrinkers
4,072 (59.5)

<7 drinks/week
1,858 (27.1)

≥7 drinks/week
897 (13.1)

Cancer Treatment Received 3, N (%)

Surgery
3.528 (51.5)

Radiation therapy
3,752 (54.8)

Chemotherapy
2,929 (42.8)

Hormonal therapy
5,877 (85.9)

Tumor Estrogen receptor (ER) Status

Positive
2,409 (35.2)

Negative
924 (13.5)

Undetermined
127 (1.86)

Missing/unkown
3,385 (49.5)

Tumor Progesterone reception (PR) Status

Positive
2,189 (32.0)

Negative
1,109 (16.2)

Undetermined
118 (1.72)

Missing/unknown
3,429 (50.1)

Weight status was defined as underweight (BMI<18.5 kg/m2), normal weight (BMI = 18.5–24.9 kg/m2), overweight (BMI = 25–29.9 kg/m2), and obese (BMI ≥30 kg/m2).

Physical activity was defined as active if ≤,150 minutes/week of moderate and/or vigorous physical activities, and inactive otherwise.

Based on self‐report.

Dietary Intake of Isoflavone and All‐Cause Mortality in Women with Breast Cancer: the Breast Cancer Family Registry

Number of Deaths
Person Years
HR (95% CI)1
HR (95% CI)2

Among All Women (n=6,842)

Total Isoflavone, mg/d

Q1 (< 0.340)
413
15,167
1.0 (ref.)
1.00 (ref.)

Q2 (0.340 – 0.669)
392
15,432
0.96 (0.83,1.11)
1.03 (0.89,1.19)

Q3 (0.670 – 1.470)
338
15,604
0.82 (0.70,0.95)
0.89 (0.76,1.04)

Q4 (≥1.471)
258
14,982
0.65 (0.55,0.77)
0.75 (0.62,0.91)

P trend <0.0001
P trend = 0.002

Genistein, mg/d

Q1 (<0.167)
409
15,141
1.00 (ref.)
1.00 (ref.)

Q2 (0.167–0.334)
405
15,298
1.00 (0.87,1.16)
1.05 (0.91,1.22)

Q3 (0.335–0.733)
330
15,795
0.79 (0.67,0.92)
0.83 (0.71,0.98)

Q4 (≥0.734)
257
14,951
0.65 (0.55,0.77)
0.73 (0.60,0.88)

P trend <0.0001
P trend = 0.0002

Daidzein, mg/d

Q1 (<0.134)
424
15,013
1.00 (ref.)
1.00 (ref.)

Q2 (0.134–0.268)
376
15,572
0.86 (0.75,1.00)
0.91 (0.79,1.06)

Q3 (0.269–0.623)
337
15,693
0.76 (0.65,0.89)
0.82 (0.70,0.97)

Q4 (≥0.624)
264
14,907
0.63 (0.54,0.75)
0.73 (0.61,0.89)

P trend <0.0001
P trend =0.0007

Glycitein, mg/d

Q1 (<0.021)
430
15,204
1.00 (ref.)
1.00 (ref.)

Q2 (0.021–0.054)
372
15,353
0.86 (0.74,0.99)
0.92 (0.79,1.07)

Q3 (0.055–0.148)
341
15,478
0.79 (0.68,0.92)
0.85 (0.72,0.99)

Q4 (≥0.149)
258
15,149
0.61 (0.51,0.72)
0.71 (0.58,0.85)

P trend <0.0001
P trend =0.0003

Adjusted for age (continuous), study site, and total caloric intake (quartiles).

Additionally adjusted for race/ethnicity (non‐Hispanic White, Black, Hispanic, and Asian/Pacific Islander/other), education (high school or less, some college or bachelor's degree, or graduate degree), total fiber intake (quartiles). Health Eating Index (HEI)‐2010 (quartiles), treatment type (surgery, radiation, chemotherapy, and hormone therapy), physical activity (active, inactive), BMI (<25, 25–29.9, ≥30 kg/m2), alcohol use (never, <7 drinks/wk, ≥7 drinks/wk), smoking status (never, ever), and pack‐years (continuous).