Table 1.
Clinical effects of isoflavones and soy protein on markers of breast cancer risk
| Author, Year/(Reference) | Subject No./Intervention Product/Isoflavone Exposure (mg/d)1 | Study Length | Subject Description | Sampling Method | Primary Measures of Interest | Results | ||
| Breast Biopsies | ||||||||
| Cheng, 2007/(61) | 25/placebo 26/tablets/36 |
12 wk | Healthy post-menopausal women, age range, 49–69 y; mean age, ~57 | Middle-needle biopsy of breast tissue using ultrasound to identify glandular tissue | ERα, ERβ, ERβcx,2 and PRα/β3 expression, Ki67 | NSE5 for any measure. The proliferation marker, Ki67, was seen in 0% to 3% of samples, and no significant change was induced by isoflavone treatment. | ||
| Sartippour, 2004/(88) | 26/historical controls 17/tablets/120 |
~22 d | Women with invasive/infiltrating breast cancer diagnosed by core-needle biopsy; mean age, ~61 y | Breast cancer biopsies and surgical specimens | ER & PR expression, p53, her-2/neu, DNA flow analysis, apoptosis and mitosis | NSE but trend toward an ↑ in the ratio of cells undergoing apoptosis versus mitosis in isoflavone (IF) group | ||
| Apoptosis/Mitosis* | ||||||||
| Control | Isoflavone | |||||||
| Pre | 6.5 ± 7.0 | 5.5 ± 4.7 | ||||||
| Post | 3.3 ± 3.4 | 5.8 ± 8.3 | ||||||
| *Apoptosis and mitosis counts/high-power fields, means ± SD | ||||||||
| Palomares, 2004/(89) | 9/placebo 9/tablets/100 |
11.7 mo | Postmenopausal women previously diagnosed with in-situ or early stage invasive (Stage I-II) breast cancer; mean age, 56.9 ± 1.4 y | Ultrasound-guided 14-gauge core biopsies of the contralateral breast | Histology, ER/PR expression, Ki67 | NSE for any measure. | ||
| Breast tissue histology* | PBO | IF | ||||||
| Normal | 5 | 5 | ||||||
| Hyperplasia w/o atypia | 2 | 2 | ||||||
| Hyperplasia with atypia | 0 | 1 | ||||||
| Inadequate | 2 | 1 | ||||||
| Ki67 index* (mean) | 5.9% | 5.4% | ||||||
| (SD) | 5.2% | 6.5% | ||||||
| * values represent number of subjects | ||||||||
| Hargreaves, 1999/(90) | 53/UD5 28/UD + 60 g soy protein/~45 |
14 d | Premenopausal women undergoing breast biopsy or definitive surgery for breast cancer;6 mean age, ~33 y | Grossly normal breast tissue (~1 cm3) excised at least 1 cm from the site of the lesion. | ER/PR expression, thymidine and Bcl-2 labeling, Ki67 | NSE for any measure | ||
| Ki67 labeling index | ||||||||
| Wks 1 & 2 | Wks 3 & 4 | |||||||
| Control | 3.16 ± 3.08 | 6.03 ± 4.27 | ||||||
| Soy | 4.76 ± 6.16 | 6.17 ± 7.0 | ||||||
| Values are mean ± SD | ||||||||
| Mammograms (Breast Tissue Density) | ||||||||
| Tice (in press)/(98)7 | 23/UD+25 g casein 24/UD+25 g ISP8/50 |
6 mo | Premenopausal women at high risk of breast cancer (defined by Gail risk ≥ 1.67% and mammographic breast density ≥ 50%) | Timed to late follicular phase (Day 10). Computer-aided contour method. Pre/post films read paired in random order at close of study, CC view and single reader | NSE | |||
| Powles, 2008/(99) | Premenopausal 111/tablets/409 111/Placebo/0 Postmenopausal 8/tablets/409 11/placebo/0 |
3 y | Healthy women aged between 35 and 70 y with at least one first-degree relative with breast cancer | Mammograms were conducted on both breasts. All film images were digitalized and breast density was determined from the digital or digitalized images. Breast density was measured on a scale of 0–100 with higher figures representing more dense breasts | Mean change (%) from baseline plus 95% CI Premenopausal | |||
| Isoflavone | 3.03 | (-5.53 – -0.54) | ||||||
| Placebo | 6.60 | (-9.04 – -4.16) | ||||||
| Postmenopausa | ||||||||
| Isoflavone | -6.9 | (-11.6 – -2.1) | ||||||
| Placebo | -8.0 | (-15.7 – -0.2) | ||||||
| Maskarinec, 2004/(96) | 103/UD 98/2 servings soyfoods/~50 |
~2.2 y | Healthy premenopausal women; average age, ~43 y | Computer-assisted density assessment. All mammograms for 1 woman were assessed during the same session, but the reader was unaware of the group status or the time sequence of the mammograms. | Breast tissue density (%) | |||
| Control | Soy | |||||||
| Baseline | 48.1 ± 25.2 | 45.6 ± 23.3 | ||||||
| Final | 43.2 ± 24.3 | 40.5 ± 23.7 | ||||||
| Change | 4.1 ± 10.2 | 2.8 ± 9.6 | ||||||
| Values are means ± SD. NSE | ||||||||
| Atkinson, 2004/(97) | 61/Placebo 56/tablets/43.59 |
12 mo | Postmenopausal women with Wolfe P2 or DY breast patterns; age range, 49–65 y; mean age, ~55 | Percent densities assigned by drawing and measuring a cross on a 100 mm line (representing 0–100% density) | Reader 1: in the placebo and isoflavone groups respectively, 22% and 18% of women changed to a more lucent Wolfe pattern, 78% and 80% did not change, and 0% and 2% changed to a more dense Wolfe pattern. Reader 2: in the isoflavone and placebo groups, respectively, 15% and 19% of women changed to a more lucent Wolfe pattern, 84% and 80% did not change, and 1% and 1% changed to a more dense Wolfe pattern. NSE of isoflavone treatment | |||
| Maskarinec, 2003/(95) | 15/UD 15/UD + tablets/76 |
~12 mo | Healthy pre-menopausal women; mean age, 42 y | Computer-assisted density assessment. Left and right cranio-caudal views of the mammograms (all free of malignancies) were scanned into a PC using a Cobrascan CX-612-T digitizer. | Percent breast tissue density | |||
| Control | Soy | |||||||
| Initial | 49.5 ± 12.6 | 34.6 ± 18.8 | ||||||
| Final | 49.9 ± 12.8 | 37.1 ± 16.5 | ||||||
| Values are means ± SD. NSE | ||||||||
| Nipple Aspirate Fluid (NAF) | ||||||||
| Qin, 2007/(103) | 15/tablets/24 19/tablets/42 |
~1 mo | Premenopausal women with no history of atypia, in situ or invasive breast cancer; age range, 19–54; median, ~37 y | NAF was collected before and after one menstrual cycle. Samples from the left and right breast were kept separate | Estrogen marker, complement (C)3 and cell cytology | NSE | ||
| Hargreaves, 1999/(90) | 53/UD 28/UD + 60 g soy protein/~45 |
14 d | Premenopausal women undergoing breast biopsy or definitive surgery for breast cancer;6 mean age, ~33 y | NAF obtained by bimanual, four-quadrant compression of the breast. Fluid was collected into capillary tubes, and the volume of neat nipple secretion was calculated by multiplying the length (in millimeters) of nipple fluid in the tube by the cross-sectional area of the capillary tube lumen | Apolipoprotein D (apoD) and pS2 levels | Statistically significant ↑ and ↓ in pS2 and apoD levels, respectively (P ≤ 0.002). | ||
| Petrakis, 1996/(102) | 24/UD + 37.4 g ISP/75 | 6 mo | Premenpausal (n = 14) and postmenopausal women (N = 10) | NAF was obtained with a Sartorius-type breast pump consisting of a 15-cc syringe attached to a small cup by a short piece of plastic tubing | NAF volume, gross cystic disease fluid protein (GCDFP-15) concentration, and NAF cytology. | Statistically significant ↑ in fluid volume and ↓ in GCDFP-15 in premenopausal women only. Epithelial hyperplasia in 7 of 24 women during and after ISP intake. | ||
1 Daily isoflavone intake expressed as aglycone units; 2 ER, estrogen receptor; 3 PR, progesterone receptor; 4 NSE, no statistically significant effects; 5 UD, usual diet; 6Women diagnosed with benign breast disease included fibroadenoma (n = 38), reduction mammoplasty (n = 10), fibrocystic masses (n = 9), duct ectasia (n = 6), sclerosing adenosis (n = 3), lipoma (n = 1), and accessory breast removal (n = 1); thirteen cases of breast cancer were of the invasive ductal type, and 3 were ductal carcinoma in situ; fourteen patients were confirmed as taking oral contraceptives at the time of surgery, and 61 were parous; twenty (71.4%) patients completed 13–14 days of soy supplementation, 4 (14.3%) completed 10–12 days, and 4 (14.3%) completed 8–9 days of soy supplementation; however, all patients said they had taken the last soy tablet 24 h before surgery; 7 Details are described in reference; 8 ISP, isolated soy protein; 9 Isoflavones derived from red clover.