Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy
Xinmei Kang, MD PhD,
Qingyuan Zhang, MD PhD,
Shuhuai Wang, MD,
Xu Huang, MD and
Shi Jin, MD
From the Departments of Medical Oncology (Kang, Zhang, Huang, Jin) and
Pathology (Wang), Cancer Hospital of Harbin Medical University, Harbin,
Background: The intake of soy isoflavones among women with breastcancer has become a public health concern, because these compoundshave weak estrogenic effects. There is little clinical evidence about their safety for patients with breast cancer who are receiving adjuvant endocrine therapy.
Methods: For patients who underwent surgery for breast cancerbetween August 2002 and July 2003 and who were receiving adjuvantendocrine therapy, we examined associations between dietary intake of soy isoflavones and recurrence of breast cancer and death. We measured dietary intake of soy isoflavones at baseline using a validated food frequency questionnaire. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) by meansof multivariable Cox proportional hazards regression models.We further stratified the analyses by hormonal receptor statusand endocrine therapy.
Results: The median follow-up period for the 524 patients inthis study was 5.1 years. Among premenopausal patients, theoverall death rate (30.6%) was not related to intake of soyisoflavones (HR = 1.05, 95% CI 0.78–1.71 for the highes tquartile [> 42.3 mg/day] v. the lowest quartile [< 15.2mg/day], p for trend = 0.87). Relative to post-menopausal patientsin the lowest quartile of soy isoflavone intake, the risk ofrecurrence for post-menopausal patients in the highest quartile was significantly lower (HR = 0.67, 95% CI 0.54–0.85,p for trend = 0.02). Inverse associations were observed in patientswith estrogen and progesterone receptor positive disease andthose receiving anastrozole therapy.
Interpretation: High dietary intake of soy isoflavones was associated with lower risk of recurrence among post-menopausal patients with breast cancer positive for estrogen and progesterone receptorand those who were receiving anastrozole as endocrine therapy.
Prospective cohort study of soy food intake and colorectal cancer risk in women Gong Yang1,2,3, Xiao-Ou Shu1,2,3, Honglan Li1,2,3, Wong-Ho Chow1,2,3, Hui Cai1,2,3, Xianglan Zhang1,2,3, Yu-Tang Gao1,2,3 and Wei Zheng1,2,3 1
From the Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203 (GY, X-OS, HC, XZ, and WZ);the Shanghai Cancer Institute, Shanghai, China (HL and Y-TG);and the Division of Cancer Epidemiology and Genetics, NationalCancer Institute, NIH, DHHS, Bethesda, MD (W-HC).
Abstract Background: Soy and some of its constituents, such as isoflavones,have been shown to have cancer-inhibitory activities in experimentalstudies. Data from epidemiologic studies linking usual soy foodintake with colorectal cancer are limited and inconsistent.
Objective: The objective was to investigate whether soy food intake is associated with colorectal cancer risk.
Design: We prospectively examined 68,412 women aged 40–70y and free of cancer and diabetes at enrollment. Usual soy food intake was assessed at baseline (1997–2000) and reassessed during the first follow-up (2000–2002) through in-person interviews with a validated food-frequency questionnaire. We excluded the first year of observation to minimize lifestyle changes related to preclinical disease.
Results: During a mean follow-up of 6.4 y, 321 incident colorectalcancer cases were identified. After adjustment for potential confounding factors, total soy food intake was inversely associated with colorectal cancer risk. Each 5-g/d increment in intake of soy foods as assessed by dry weight [equivalent to 1 oz (28.35g) tofu/d] was associated with an 8% reduction in risk (95%CI: 3%, 14%). Women in the highest tertile of intake had a multivariaterelative risk of 0.67 (95% CI: 0.49, 0.90) compared with those in the lowest tertile (P for trend = 0.008). This inverse association was primarily confined to postmenopausal women. Similar results were also found for intakes of soy protein and isoflavones.
Conclusion:This prospective study suggests that consumption of soy foods may reduce the risk of colorectal cancer in postmenopausal women.
Source:American Journal of Clinical Nutrition, doi:10.3945/ajcn.2008.26742 Vol. 89, No. 2, 577-583, February 2009 LINK TO FULL ARTICLE
Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on the growth of estrogen-dependent human breast carcinoma in mice
Zhiming Mai, George L. Blackburn, and Jin-Rong Zhou*
Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel, Deaconess Medical Center, Harvard Medical School, Burlington-5, 330, Brookline Avenue, Boston, MA 02215, USA
The objective of this work was to determine the interactive effects between soy bioactive components and tamoxifen (TAM) on prevention of estrogen-dependent breast cancer (BRCA). We initially investigated the effects of soy isoflavone genistein and TAM on the growth and cell cycle progression of estrogen-dependent MCF-7 human BRCA cells, and on the expression of ERα, pS2 and EGFR genes in vitro. Genistein or TAM alone inhibited the growth of MCF-7 cells in part via G1 phase arrest, but their combinations showed suggestive antagonistic effects. We further evaluated the effects of bioactive soy components and TAM on the growth inhibition of MCF-7 tumors in a clinically relevant breast tumor model. TAM and bioactive soy components, genistein and soy phytochemical concentrate (SPC), delayed the growth of MCF-7 tumors. The combination of TAM with genistein or SPC, especially at the lower dose of TAM, had synergistic effects on delaying the growth of MCF-7 tumors. Biomarker determination suggests that the combination of TAM and soy components may synergistically delay the growth of MCF-7 tumors via their combined effects on induction of tumor cell apoptosis and inhibition of tumor cell proliferation. In addition, genistein and TAM combination synergistically delayed the growth of breast tumor via decreased estrogen level and activity, and down-regulation of EGFR expression. The results from our studies suggest that further investigations may be warranted to determine if the combination of TAM and bioactive soy components may be used for prevention and/or treatment of estrogen-dependent BRCA.
1Department of Urology, College of Physicians and Surgeons and 2 Department of Biostatistics, School of Public Health, Columbia University Medical Center, New York, New York
Abstract Purpose: Isoflavones have anticancer activities, but naturally occurring isoflavones are predominantly glycosylated and poorly absorbed. Genistein combined polysaccharide (GCP; Amino Up Chemical Co., Sapporo, Japan), is a fermentation product of soy extract and basidiomycetes mycillae that is enriched in biologically active aglycone isoflavones. This study analyzes GCP in vitro and in vivo for potential utility as a prostate cancer chemopreventative agent.
Experimental Design: Androgen-sensitive LNCaP and androgen-independent PC-3 cells were grown with various concentrations of GCP. In vitro cell growth was analyzed by the WST-1 assay, and apoptosis was assessed by fluorescence-activated cell sorting and detection of poly(ADP-ribose) polymerase cleavage using Western blot techniques. Effects of GCP on expression of cell cycle-regulatory proteins p53 (LNCaP only), p21, and p27 and the protein kinase Akt were considered using Western blot techniques. An in vivo LNCaP xenograft model was used to study the effects of a 2% GCP-supplemented diet on tumor growth in comparison with a control diet.
Results: GCP significantly suppressed LNCaP and PC-3 cell growth over 72 h (89% and 78% in LNCaP and PC-3, respectively, at 10 μg/ml; P < 0.0001). This reduction was associated with apoptosis in LNCaP cells, but not in PC-3 cells. GCP induced p27 and p53 (LNCaP only) protein expression within 6 h and suppressed phosphorylated Akt in both cell lines. The 2% GCP-supplemented diet significantly slowed LNCaP tumor growth, increasing apoptosis (P < 0.001), and decreasing proliferation (P < 0.001) over 4 weeks.
Conclusions: GCP has potent growth-inhibitory effects against prostate cancer cell lines in vitro and in vivo. These data suggest GCP has potential as an effective chemopreventive agent against prostate cancer cell growth.
Differential effects of whole soy extract and soy isoflavones on apoptosis in prostate cancer cells
Anna Hsu1, Tammy M Bray1,2, William G Helferich3, Daniel R Doerge4 and Emily Ho1,2,
1 Department of Nutrition and Exercise Sciences, 103 Milam Hall 2 Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331 3 Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, IL 61801 4 National Center for Toxicological Research, Jefferson, AR 72079, USA
Abstract Previous studies have suggested that soy isoflavones exert anticarcinogenic effects against prostate cancer. We propose that soy extracts,containing a mixture of soy isoflavones and other bioactive components, would be a more potent chemo-preventive agent than individual soy isoflavones. We compared the apoptotic effects of whole soy extracts and individual soy isoflavones, genistein and daidzein, on prostate cancer cells. The soy extract contained 50% w/w of total isoflavones with approximately 1:5.5:3.5 ratios of genistin, daidzin and glycitin, respectively. Benign prostate hyperplasia (BPH-1), LnCap and PC3 cells were treated with varying concentrations of soy extract, genistein or daidzein and analyzed for cell cycle alterations and induction of apoptosis. At equal concentrations (25 µmol/L), soy extract induced a significantly higher percentage of cells undergoing apoptosis than genisteinor daidzein (P < 0.001). No significant changes in cell cycle arrest or apoptosis were observed in non-cancerous BPH-1 cells treated with soy extract, suggesting that the effects of soy extract may be tumor cell specific. On the contrary, both genistein and daidzein induced apoptosis in BPH-1 cells, suggesting that individual isoflavones may have cytotoxicity in non-cancerouscells. Soy extracts also increased Bax expression in PC3 cells,but no significant changes in nuclear factor B (NFB) activation were detected, suggesting that the induction of apoptosis was independent of the NFB pathway. Food products that bear a combination of active compounds may be more efficacious and safer as chemo-preventive agents than individual compounds. This ‘whole-food’-based approach is significant for the development of public health recommendations for prostate cancer prevention.