Breast Cancer

Vitamin D and breast cancer

Nielsen LR, Mosekilde L. Ugeskr Laeger. 2007 Apr 2;169(14):1299-302.

Arhus Universitetshospital, Arhus Sygehus, Medicinsk-endokrinologisk Afdeling C. rejnmark@post6.tele.dk
Active vitamin D increases the differentiation and exerts antiproliferative effects in cancer cells. Recent data suggest that vitamin D is activated locally in cancer cells. Ecologic studies have shown an inverse correlation between breast cancer mortality and sun exposure and dietary vitamin D intake. In clinical studies an impaired vitamin D status is associated with a 20-30% increased breast cancer incidence and 10-20% increased mortality. As vitamin D insufficiency is common, it is important to clarify whether vitamin D status affects the risk and prognosis of breast cancer

 

Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo.

Cancer Lett. 2007 Jan 8;245(1-2):232-41. Epub 2006 Mar 6. Links

Thangapazham RL, Singh AK, Sharma A, Warren J, Gaddipati JP, Maheshwari RK.
Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Tea [Camellia sinensis (Theaceae)] intake is second only to water in terms of worldwide popularity as a beverage. The Green tea polyphenols have been shown to have a protective effect in prostate cancer in various pre-clinical animal models and has been reported to be effective in several other cancer types as well. An inverse association between the risk of breast cancer and the intake of green tea has also been reported in Asian Americans. Several epidemiological studies have shown that breast cancer progression is delayed in the Asian population that consumes green tea on regular basis. In this study, we report the effectiveness of green tea polyphenols (GTP) and its constituent Epigallocatechin Gallate (EGCG) in tumor regression using both in-vitro cell culture models and in vivo athymic nude mice models of breast cancer. The anti-proliferative effect of GTP and EGCG on the growth of human breast cancer MDA-MB-231 cell was studied using a tetrazolium dye-based (MTT) assay. Both GTP and EGCG treatment had the ability to arrest the cell cycle at G1 phase as assessed by flow cytometry. The expression of Cyclin D, Cyclin E, CDK 4, CDK 1 and PCNA were down regulated over the time in GTP and EGCG treated experimental group, compared to the untreated control group as evaluated by western blot analysis for cell cycle proteins, which corroborated the G1 block. Nude mice inoculated with human breast cancer MDA-MB-231 cells and treated with GTP and EGCG were effective in delaying the tumor incidence as well as reducing the tumor burden when compared to the water fed and similarly handled control. GTP and EGCG treatment were also found to induce apoptosis and inhibit the proliferation when the tumor tissue sections were examined by immunohistochemistry. Our results suggest that GTP and EGCG treatment inhibits proliferation and induce apoptosis of MDA-MB-231 cells in-vitro and in-vivo. All together, these data sustain our contention that GTP and EGCG have anti-tumor properties.

Growth inhibitory and antimetastatic effect of green tea polyphenols on metastasis-specific mouse mammary carcinoma 4T1 cells in vitro and in vivo systems.

Baliga MS, Meleth S, Katiyar SK. Clin Cancer Res. 2005 Mar 1;11(5):1918-27. Links
Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA.
PURPOSE: Breast cancer is the second leading cause of cancer-related deaths among females. Dietary habits may have a role in breast cancer risk and prevention as well. Here, we examined the effect of green tea polyphenols (GTP) on growth and metastasis of highly metastatic mouse mammary carcinoma 4T1 cells in vitro and in vivo systems.

EXPERIMENTAL DESIGN: 4T1 cells were treated with (-)-epigallocatechin-3-gallate (EGCG), and the effect was determined on cellular proliferation, induction of apoptosis, proapoptosis, and antiapoptotic proteins of Bcl-2 family, and caspase 3 and poly(ADP-ribose) polymerase activation following 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and Western blot analysis. Anticarcinogenic and antimetastatic effect of GTP in 4T1 cells was assessed in immunocompetent BALB/c mice.

RESULTS: Treatment of 4T1 cells with EGCG resulted in inhibition of cell proliferation, induction of apoptosis in dose- and time-dependent manner. The increase in apoptosis was accompanied with decrease in the protein expression of Bcl-2 concomitantly increase in Bax, cytochrome c release, Apaf-1, and cleavage of caspase 3 and PARP proteins. Treatment of EGCG-rich GTP in drinking water to 4T1 cells bearing BALB/c mice resulted in reduction of tumor growth accompanied with increase in Bax/Bcl-2 ratio, reduction in proliferating cell nuclear antigen and activation of caspase 3 in tumors. Metastasis of tumor cells to lungs was inhibited and survival period of animals was increased after green tea treatment.

CONCLUSION: This study suggests that GTP have the ability to prevent the development of breast cancer and its metastasis; however, further in vivo studies are required to identify the molecular targets.

Coffee, tea, and caffeine consumption and breast cancer incidence in a cohort of Swedish women.

Michels KB, Holmberg L, Bergkvist L, Wolk A.
Obstetrics & Gynecology Epidemiology Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

PURPOSE: Coffee, caffeinated tea, and caffeine have been suggested to play a role in breast carcinogenesis or in the promotion or inhibition of tumor growth. Prior epidemiologic evidence has not supported an overall association between consumption of caffeinated beverages and risk of breast cancer, but consumption in some studies was low.

METHODS: We studied this relation in the Swedish Mammography Screening Cohort, a large population-based prospective cohort study in Sweden comprising 59,036 women aged 40-76 years. Sweden has the highest coffee consumption per capita in the world.

RESULTS: During 508,267 person-years of follow-up, 1271 cases of invasive breast cancer were diagnosed. Women who reported drinking 4 or more cups of coffee per day had a covariate-adjusted hazard ratio of breast cancer of 0.94 [95% confidence interval (CI) 0.75-1.28] compared to women who reported drinking 1 cup a week or less. The corresponding hazard ratio for tea consumption was 1.13 (95% CI 0.91-1.40). Similarly, women in the highest quintile of self-reported caffeine intake had a hazard ratio of beast cancer of 1.04 (95% CI 0.87-1.24) compared to women in the lowest quintile.

CONCLUSIONS: In this large cohort of Swedish women, consumption of coffee, tea, and caffeine was not associated with breast cancer incidence.

Alcohol Intake and Cigarette Smoking and Risk of a Contralateral Breast Cancer: The Women's Environmental Cancer and Radiation Epidemiology Study.

Knight JA, Bernstein L, Largent J, Capanu M, Begg CB, Mellemkjær L, Lynch CF, Malone KE, Reiner AS, Liang X, Haile RW, Boice JD Jr; WECARE Study Collaborative Group, Bernstein JL. Am J Epidemiol. 2009 Feb 11.

Women with primary breast cancer are at increased risk of developing second primary breast cancer. Few studies have evaluated risk factors for the development of asynchronous contralateral breast cancer in women with breast cancer.

In the Women's Environmental Cancer and Radiation Epidemiology Study (1985-2001), the roles of alcohol and smoking were examined in 708 women with asynchronous contralateral breast cancer (cases) compared with 1,399 women with unilateral breast cancer (controls). Cases and controls aged less than 55 years at first breast cancer diagnosis were identified from 5 population-based cancer registries in the United States and Denmark. Controls were matched to cases on birth year, diagnosis year, registry region, and race and countermatched on radiation treatment. Risk factor information was collected by telephone interview. Rate ratios and 95% confidence intervals were estimated by using conditional logistic regression.

Ever regular drinking was associated with an increased risk of asynchronous contralateral breast cancer (rate ratio = 1.3, 95% confidence interval: 1.0, 1.6), and the risk increased with increasing duration (P = 0.03). Smoking was not related to asynchronous contralateral breast cancer. In this, the largest study of asynchronous contralateral breast cancer to date, alcohol is a risk factor for the disease, as it is for a first primary breast cancer.