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Breast Cancer

physician assistant

 

Introduction:

The following information focuses on potential Integrative Medicine interventions for both breast cancer prevention and possibilities for improvement of breast cancer survival. The gynecologist is of highest importance in guidance and performance of screening for breast cancer by a greater expertise in breast exams and in recommending mammogram intervals. It is vital that the patient adhere to the gynecologist recommendations and be compliant with clinic appointments to obtain the greatest possible benefit. Careful attention should be provided to signs and symptoms of breast cancer which include painless hard or irregular lumps, nipple discharge, breast swelling, skin ulcers, breast pains, skin irregularities, bone pain, redness of the skin, swelling under the armpits, and weight loss. Men may also get breast cancer but it is much less common than in women.

 

Risk factors of breast cancer:

Risk factors which cannot be changed: These include age over 50, early age onset of menstrual periods, genetic factors, and family history of not only breast cancer but also ovarian, uterine, or colon cancers.

 

Modifiable risk factors of breast cancer:

Risk factors that can be modified include obesity, use of hormone replacement therapy, radiation exposure, any use of alcohol, women without history of childbirth, women giving birth to children only after age 30, and exposure to diethylstilbestrol (DES) to prevent miscarriage (given in the mid-1900s).

Alcohol consumption was associated with an increased risk of breast cancer (BrCa). In a cohort study of 70,033 women, 2,829 developed BrCa. Risk of BrCa significantly increased at a total alcohol consumption starting at 1-2 drinks/day. Specifically, at 1-2 drinks/day risk of BrCa increased by 21% (RR=1.21, p=0.01) and at > or = 3 drinks/d risk increased by 38% (RR=1.38, p=0.002). Increased BrCa risk was concentrated in women with estrogen receptor positive tumours. Estrogen is a female sex hormone that stimulates some breast cancers to grow by triggering particular proteins (receptors) in the cancer cells. Choice of wine, liquor, beer or type of wine (red, white, etc) had no major impact on results. (1)

Women are also at lower risk of breast cancer if they have had multiple childbirths or pregnancy when young.

 

U.S. Preventive Services Task Force (USPSTF) and breast cancer:

USPSTF recommendations for breast cancer screening (2):

For women aged 50 to 74 years the USPSTF recommends mammography screening every two years (biennial). Earlier or annual mammogram screening is not done anymore after USPSTF determined that there is “at least moderate certainty that the net benefit is small.”

For women younger than 50 years, biennial screening should be based on individual patient history. For instance, if a patient has a close relative with breast cancer at a young age, mammography would be done more frequently due to increased risk.

The USPSTF recommends against teaching breast self-examination since 2009 after concluding that breast self-exam does not save lives or detect breast cancer at an earlier stage. Breast self-exam is now promoted as optional by the USPSTF and Mayo Clinic because it does not affect mortality according to research.

 

U.S. Preventive Services Task Force (USPSTF) recommendations for breast cancer chemoprevention (3):

According to the USPSTF, clinicians are recommended to talk about the benefits and harms of chemoprevention with women at high risk for breast cancer and who have a low risk of adverse effects of chemoprevention.

Routine use of tamoxifen or raloxifene primary prevention of breast cancer in women at low or average risk of breast cancer is recommended against by the USPSTF. (2)

 

U.S. Preventive Services Task Force (USPSTF) and genetic factors (4):

According to the USPSTF, women with a family history with an increased risk for harmful mutations in BRCA1 or BRCA2 genes, which are associated with breast cancer, are recommended to be referred for genetic counseling and evaluation for BRCA (breast cancer susceptibility gene) testing.

The USPSTF recommends against genetic counseling or routine breast cancer testing for women with no family history of increased risk for breast cancer.

 

Breast cancer and dietary factors:

Red meat consumption and breast cancer:

Red meat consumption has been found to be associated with various forms of cancer in a multisite case-control study of 11 sites in Uruguay. High consumption of red meat was associated with about double the overall risk for breast cancer(OR= 1.97). Eating a lot of processed meat was also linked to an increased risk of breast cancer (OR= 1.53). (5)

It has long been suspected that red meat contributed to cancer risk in patients. According to a study in Italy conducted between 1983 and 1996 on patients with a red meat intake of at least 7 times per week, the incidence of cancers of breast, endometrium, and ovaries was higher. Therefore, it suggested that the reduction of red meat in the diet might lower the risk factors for these types of cancers. (6)

 

Carotenoids and breast cancer risk:

According to a large prospective study of 83,234 women (aged 33-60 years old), consumption of foods rich in specific carotenoids (plant pigments found in carrots, sweet potatoes, spinach, kale, collard greens, papaya, bell peppers, tomatoes) and vitamins A, C, and E may reduce the risk of breast cancer among premenopausal women. Increased intake of lutein and zeaxanthin (both carotenoids), and vitamin A supplements, as well as beta-carotene from food were found to lower the risk of breast cancer in premenopausal women, but the link was found to be weak. However among women with a family history of breast cancer, this association was strong. Researchers reported that higher intake of beta-carotene was associated with a moderately reduced risk of breast cancer among women consuming 15 grams per day or more. Furthermore, premenopausal women eating at least 5 servings of fruits and vegetables per day had a significant reduction of breast cancer risk compared to women who had less than 2 servings per day. Premenopausal women with a family history of breast cancer who consumed more than 5 servings of fruits and vegetables per day received the greatest benefit from carotenoids with a moderately reduced risk of breast cancer. (7)

 

Caloric restriction and breast cancer:

Michels and Ekbom conducted a retrospective cohort study of the impact of caloric restriction on the development of breast cancer. Specifically, they indentified 7,303 women who were hospitalized for anorexia nervosa before age 40 to determine if these women had a lower incidence of breast cancer than was expected in the general population. The authors used data from several Swedish between 1965 and 1998. The women were identified as nulliparous (not having any previous childbirth) or parous (those who have had at least one childbirth). Results indicated that women who were diagnosed with anorexia before 40 years of age had a 53% lower incidence of breast cancer than women in the Swedish general population.  The reduced incidence of breast cancer in the subgroups was 23% in nulliparous women and 76% in parous women. These results suggest that caloric restriction may be associated with a protective benefit against breast cancer. (8)

 

Diet, exercise, and breast cancer:

Diet and exercise reduced serum markers for breast cancer in vivo, reduced tumor cell growth in vitro, and caused apoptosis of breast cancer cells in vitro. A study involving 38 overweight or obese postmenopausal women adhered to a low-fat (10-15% kcal from fat), high-fiber (30-40 g per 1,000 kcal/d) diet, and participated in a daily exercise class for 2 weeks.  The diet and exercise was found to reduce several serum markers for breast cancer including estrogen, obesity, insulin and insulin-like growth factor-I (IGF-I), even while subjects remained overweight or obese. The in-vitro analysis used serum drawn from the study group before and after the 2 week intervention and placed it with cancer cells. It was found that the growth in different types of breast cancer cell lines was reduced by 6.6-18.5%. Cell death of several different cell types of breast cancer also increased by 20-30% after the intervention. (9)

 

Diet and breast cancer survival:

In a study by Thompson, CA, a healthy diet may help breast cancer patients live longer, but does not appear to significantly reduce risk of breast cancer recurrence. A summary report of studies examined the risk of breast cancer on dietary intervention. A literature review found that diets rich in fiber and low in fat may only weakly protect against breast cancer. This study found that total food consumption and alcohol appear to be positively associated with risk of breast cancer. Eating fruits and vegetables is has no clear link to risk of breast cancer. Obesity was found to be a risk factor for postmenopausal disease (breast cancer after menopause). Weight gain in adults was also associated with increased risk. It was found that healthy diet habits can help breast cancer patients live longer, but not significantly reduce risk of breast cancer recurrence. (10)

 

Brassica, (Chinese cabbage) and breast cancer:

A diet rich in Brassica, Chinese cabbage appeared to reduce the risk of breast cancer. A case control investigation was done for risk of breast cancer among 337 women in Shanghai, China with a diet rich in Brassica, Chinese cabbage. Urine samples were take from each women and levels of isothiocyanates (ITC), or the byproduct formed as the body metabolizes Brassica, were measured. Women estimated to consume the largest amounts of Brassica showed an 18% lower risk of breast cancer, and a 32% lower risk of postmenopausal breast cancer. In the same group of Chinese women, when researchers assessed exposure to brassica by urinary excretion, women who excreted the most ITC later developed only half as much breast cancer as women who excreted the least. The study concluded that Chinese women who consumed lots of Brassica vegetables, as measured by urinary ITC biomarker, significantly reduced their breast cancer risk. (11)

 

Dietary lignans and breast cancer survival:

A study looked at the association between dietary lignin intake and survival. Lignans are antioxidants and phytoestrogens (chemicals that can act like hormone estrogen) found in a variety of plants, which includes flax seeds, pumpkin seeds, rye, soybeans, broccoli and some berries. However, flax seed have the highest amount of lignans available from common nutritional sources. The data used in this study came from 1,122 women diagnosed with breast cancer between 1996 and 2001. Diet in the 12-24 months before diagnosis was assessed. For the women enrolled in this study, the main food sources of lignans were dark bread, peaches, coffee, broccoli and winter squash. Researchers estimated the average lignan intake among the women to be 244 mcg/day. They also found a 51% reduction in all cause mortality in those consuming higher lignan levels (the lowest risk of dying was seen in women consuming >318 mcg per day). These same women were far less likely to die of breast cancer. They had a 71% decreased risk of dying of breast cancer. The intake of dried beans was also associated with a 39% reduced risk of all-cause mortality. (12)

 

Breast cancer and mushroom intake:

Mushroom intake and the risk of breast cancer:

A case control study of 362 Korean women aged 30-65 years reported an association between mushroom consumption and decreased risk of breast cancer. Comparing the women who ate the most mushrooms against the women who ate the least mushrooms, mushroom eaters had 48% reduced risk of developing breast cancer. When the data was broken down by menopausal status, the effect was far more dramatic. The postmenopausal mushroom eaters had an 84% decreased risk of breast cancer. (13)

Mushroom consumption in premenopausal women may have a protective benefit against breast cancer. Mushroom consumption and risk of breast cancer were analyzed in 358 breast cancer patients and 360 cancer-free individuals. Comparing premenopausal women who ate the most mushrooms against the women who ate the least mushrooms, mushroom eaters had a 65% reduced risk of developing breast cancer. When the data was broken down by estrogen receptor status, the effect was stronger (70% risk reduction in women with estrogen receptor (ER)+/progesterone receptor (PR)+ than those with ER-/PR- tumors). (14)

A study from China found that women could reduce their risk of breast cancer by consuming a small amount of mushrooms. When the women in the study included green tea, their breast cancer risk decreased even more. Intake of fresh mushrooms (greater than or equal to 10 grams per day) and dried mushrooms (greater than or equal to 4 grams per day) decreased risk by 64% and 47%, respectively. When consumption of green tea was added (more than 1g of tea-leaves per day), the protective effect was 89% reduced risk in women who consumed the most green tea plus fresh mushrooms and 72% reduced risk in women who consumed the most green tea plus dried mushrooms. (15)

The Agaricus bisporus mushroom (white button mushrooms) contain large amounts vitamins and minerals as well as medicinal value. Chen et al. looked at the ability of chemicals derived from button mushrooms to inhibit aromatase (an enzyme that promotes estrogen). Fatty acids contained within the mushroom inhibited aromatase activity in cancer cells isolated from hamster ovaries. Conjugated linoleic acid was the most potent inhibitor evaluated. Cancerous mice given this substance had fewer tumors in tests with live animals. This study showed that the extract decreased proliferation of cancer cells and tumor growth without affecting cell death or apoptosis. (16)

Mushrooms are thought to protect against breast cancer cell (MFC-7) proliferation particularly because they contain chemicals that inhibit an enzyme called aromatase, which produces estrogen. “In cell” or in situ aromatase activity and cell proliferation were measured using MCF-7aro, an aromatase-transfected breast cancer cell line. Researchers showed that the white button mushroom (species Agaricus bisporus) suppresses the activity of aromatase, resulting in a reduction of estrogen production at the cell level, which is a major contributor to postmenopausal breast cancer in women. This is the reason believed that a diet high in mushrooms may be beneficial in reducing cell production of estrogen that may lead to breast cancer. (17)

 

Breast cancer and green tea intake:

A case-control study in Southeast China evaluated green tea drinking and breast cancer risk among 2018 women aged 20-87 years (1009 with breast cancer, 1009 age-matched controls). Compared to non-tea drinkers, women consuming up to 249 g/year of green tea had a 13% reduced risk (odds ratio [OR]=0.87) of developing breast cancer. Additionally, women drinking 250-499 g/year had a 32% reduced risk, women drinking 500-749 g/year had a 41% reduced risk and for women drinking at least 750 g/year of green tea had a 39% reduced risk. Therefore it appears that greater tea consumption is associated with a decrease in breast cancer risk. (18)

 

Breast cancer and yoga:

A meta-analysis of 13 randomized controlled trials examining yoga for patients with cancer, specifically breast cancer patients, found yoga was associated with reduced stress, anxiety, depression, and fatigue. Furthermore, among participants, yoga moderately increased quality of life, emotional and social function, and functional well-being. Physical function and sleep were not significantly affected. (19)

 

Breast cancer and vitamin B12 deficiency:

Researchers investigated whether breast cancer may, in part, be caused by a vitamin B12 deficiency. At Johns Hopkins University in Maryland, two large but separate blood sample donations were evaluated against cases of breast cancer. In 1974, 12,450 blood samples were donated by female volunteers. In 1989, another 14,625 women again voluntarily donated samples of their blood. Cases of breast cancer that occurred in these groups of women were then recorded and their blood samples examined. Researchers found that women who had the lowest levels of B12 in their blood, had the highest rates of breast cancer. Therefore, the authors concluded that there was a link between breast cancer risk and low B12 levels, mostly among postmenopausal women. (20)

 

Whey protein and breast cancer:

A specially prepared whey protein supplement, Immunocal, has been shown to reduce glutathione (GSH) concentration (which at high levels has been linked to tumour cells) and inhibition of growth in human breast cancer cells. In this 6 month study, 5 patients with metastatic carcinoma of the breast, 1 of the pancreas and 1 of the liver were administered 30 grams of Immunocal daily. In 6 patients GSH levels were high at the start of the study. In 2 patients tumour regression, normalization of hemoglobin and peripheral lymphocyte counts and a sustained drop of lymphocyte GSH levels towards normal were reported. Another 2 patients showed signs of tumour stabilization and increased hemoglobin levels. In 3 patients there was disease progression with a trend toward higher GSH levels. These findings suggest that whey protein may reduce the concentration of GSH in tumour cells. (21)

 

Breast cancer and calcium:

Adequate calcium intake by premenopausal women was associated with a reduced risk of breast cancer. (24)

 

Breast cancer and soy:

Research suggests that soy lowers the risk of breast cancer recurrence and increases the chances for survival in women. Findings from the Shanghai Breast Cancer Survival Study of 5,033 Chinese women found that the top 25% of high soy intake (over 15.3 grams per day) who were diagnosed with breast cancer and treated with surgery were noted to have a lower risk of breast cancer death and recurrence compared to those on a diet with little or no soy (less than 5.3 grams of soy per day). Among women with the top 25% of high soy intake, 4-year breast cancer mortality rate was 7.4 % verses 10.3% for the lowest soy intake. The breast cancer recurrence rate was 8.0% for high soy intake and 11.2 % for low soy intake. The inverse association of soy with breast cancer mortaliy and recurrence was seen regardless of estrogen receptor status and whether tamoxifen was taken or not. (25)

 

Supplements for future breast cancer treatment:

Supplements with in vitro evidence may have future applications in preventing breast cancer.

 

Curcumin and breast cancer:

Bayet-Robert M, et al performed a phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer was performed in 14 patients. Curcumin was started at a dose of 500 mg per day which was increased as tolerated until toxicity occureed. Toxicity limiting the dose to 8,000 mg per day was determined by the authors and as a result the recommended dose was 6000 mg per day for 7 days every 3 weeks combined with docetaxel was suggested. Most patients showed improvement and the author believed that 50% of patients would be expected to respond and expressed that a phase II trial should be implemented (26).

Using curcumin (turmeric) as a dietary supplement may help prevent triple negative breast cancer, which is an aggressive type of breast tumor. Researchers found that curcumin treatment at a dose of 30 micromol/mL significantly inhibited growth of breast cancer cells in vitro, compared to those untreated with this dietary supplement.  The treatment increased the level of programmed cell death from 2.76% in the control group to 26.34% in the treatment group. Additionally, the treatment decreased the expression levels of genes associated with triple negative breast cancer. (22)

 

Resveratrol and breast cancer:

Resveratrol, a chemopreventive compound found in the skin of red grapes and in other food products, was shown to inhibit growth of estrogen receptor (ER)-positive MCF-7 (a breast cancer cell line) by curving the effect of 17-beta-estradiol (E2), which promotes cell growth and gene activation of MCF-7, in a dose-dependent way. At 5 x 10(-6) M, resveratrol abolished the growth-stimulatory effect mediated by concentrations of E2 up to 10(-9) M. In summary, in the presence of estrogen, reveratrol acts as an ER resulting in the inhibition of human breast cancer cells growth. (22)

 

Indian gooseberry(Amla) and breast cancer:

Scientists tested the anti-cancer effects of phyllanthus emblica (PE), (also known as Indian gooseberry or Amla) known for its medicinal properties. In a series of experiments on mice and on human cancer cell lines, they found that an extract of PE may help slow tumor growth and promote apoptosis (a type of programmed cell death essential for stopping the proliferation of cancer cells). PE extract at 50-100 microg/mL significantly inhibited cell growth of six human cancer cell lines: lung, liver, cervical, breast, ovarian and colorectal. Additionally, researchers saw a 50% reduction of tumor numbers and volumes in mice treated with PE extract. PE extract at 25 and 50 micrograms/mL was also shown to inhibit invasiveness of breast cancer cells. These results suggest PE has anti-cancer properties against certain cancer cells. (23)

 

 

Assessment and Plan: Breast Cancer

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

References:

1.Li, Y., et al. Wine, liquor, beer and risk of breast cancer in a large population. European Journal of Cancer, 2002, 45(5), 843-850. http://www.ncbi.nlm.nih.gov/pubmed/19095438

 

2.Screening for Breast Cancer, Topic Page. July 2010. U.S. Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca.htm

 

3.Chemoprevention of Breast Cancer, Topic Page. July 2002. U.S. Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrpv.htm

 

4.Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility, Topic Page. September 2005. U.S. Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrgen.htm

 

5.Aune D, et al. Meat consumption and cancer risk: a case-control study in Uruguay. Asian Pac J Cancer Prev. (2009). http://www.ncbi.nlm.nih.gov/pubmed/19640186

 

6.“Red meat intake and cancer risk: a study in Italy.”  Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy.  Int J Caner. 2000 May 1;86(3):425-8. http://www.ncbi.nlm.nih.gov/pubmed/10760833

 

7.Zhang S, Hunter DJ, Forman MR, Rosner BA, Speizer FE, Colditz GA, Manson JE, Hankinson SE, Willett WC. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst. 1999 Mar 17;91(6):547-56. http://www.ncbi.nlm.nih.gov/pubmed/10088626

 

8.Michels KB, Ekbom A. Caloric restriction and incidence of breast cancer. JAMA. 2004 Mar 10;291(10):1226-30. http://www.ncbi.nlm.nih.gov/pubmed/15010444

 

9.Barnard R, Gonzalez J, Liva M, et al. Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro.  Nutr Cancer. 2006;55(1):28-34. http://www.ncbi.nlm.nih.gov/pubmed/16965238

 

10.Thomson CA. Diet and breast cancer: understanding risks and benefits. Nutr Clin Pract. 2012 Oct;27(5):636-50. http://www.ncbi.nlm.nih.gov/pubmed/22948801

 

11.Fowke JH, Chung FL, Jin F, et al. Urinary isothiocyanate levels, brassica, and human breast cancer. Cancer Res. 2003;63(14):3980-3986. http://www.ncbi.nlm.nih.gov/pubmed/12873994

 

12.McCann SE, Thompson LU, Nie J, Dorn J, Trevisan M, Shields PG, Ambrosone CB, Edge SB, Li HF, Kasprzak C, Freudenheim JL. Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study. Breast Cancer Res Treat 2010;122:229-235. http://www.ncbi.nlm.nih.gov/pubmed/20033482

 

13.Hong SA, Kim K, Nam SJ, et al. A case-control study on the dietary intake of mushrooms and breast cancer risk among Korean women. Int J Cancer 2008;122:919-923. http://www.ncbi.nlm.nih.gov/pubmed/17943725

 

14.Shin A, Kim J, Lim SY, Kim G, Sung MK, Lee ES, Ro J. Dietary mushroom intake and the risk of breast cancer based on hormone receptor status. Nutr Cancer. 2010;62(4):476-83. http://www.ncbi.nlm.nih.gov/pubmed/20432168

 

15.Zhang M, Huang J, Xie X, et al: Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women. Int J Cancer 2009 Mar 15;124(6):1404-1408. http://www.ncbi.nlm.nih.gov/pubmed/19048616

 

16.Chen S, Oh SR, Phung S, Hur G, Ye JJ, Kwok SL, Shrode GE, Belury M, Adams LS, Williams D. Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus). Cancer Res. 2006 Dec 15;66(24):12026-34. http://www.ncbi.nlm.nih.gov/pubmed/17178902

 

17.Grube BJ, Eng ET, Kao YC, et al: White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation. The Journal of nutrition 2001 Dec;131 (12):3288-3293. http://www.ncbi.nlm.nih.gov/pubmed/11739882

 

18.Zhang M, Holman CD, Huang JP, Xie X. Green tea and the prevention of breast cancer: a case-control study in Southeast China. Carcinogenesis. 2007;28:1074–8. http://www.ncbi.nlm.nih.gov/pubmed/17183063

 

19.Buffart LM, van Uffelen JG, Riphagen II, et al., Physical and psychosocial benefits of yoga in cancer patients and survivors, a systematic review and meta-analysis of randomized controlled trials. BMC Cancer. 2012 Nov 27;12:559. http://www.ncbi.nlm.nih.gov/pubmed/23181734

 

20.Wu K, Helzlsouer KJ, Comstock GW, et al. A prospective study on folate B12 and pyridoxal 5′-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev 1999;8:209–17. http://www.ncbi.nlm.nih.gov/pubmed/10090298

 

21.Kennedy RS, Konok GP, Bounous G, Baruchel S, Lee TD. The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I-II clinical study. Anticancer Res. 1995 Nov-Dec;15(6B):2643-9. http://www.ncbi.nlm.nih.gov/pubmed/8669840

 

22.Sun XD, Liu XE, Huang DS. Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression. Mol Med Report. 2012 Dec;6(6):1267-70. Epub 2012 Sep 26. http://www.ncbi.nlm.nih.gov/pubmed/23023821

 

22.Lu R., Serrero G. Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells. J. Cell. Physiol., 1999; 179: 297-304. http://www.ncbi.nlm.nih.gov/pubmed/10228948

 

23.Ngamkitidechakul C, Jaijoy K, Hansakul P, Soonthornchareonnon N, Sireeratawong S. Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion of human cancer cells. Phytother Res. 2010 Sep;24(9):1405-13. http://www.ncbi.nlm.nih.gov/pubmed/20812284

 

24.Chung M, Balk EM, Brendel M, Ip S, Lau J, Lee J, Lichtenstein A, Patel K, Raman G, Tatsioni A, Terasawa T, Trikalinos TA. Vitamin D and calcium: a systematic review of health outcomes. Evid Rep Technol Assess (Full Rep). 2009 Aug;(183):1-420. http://www.ncbi.nlm.nih.gov/pubmed/20629479

 

25.Shu XO, Zheng Y, Cai H, et al. Soy food intake and breast cancer survival. JAMA. 302(22):2437-43, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19996398

 

26.Bayet-Robert M, Kwiatkowski F, Leheurteur M, Gachon F, Planchat E, Abrial C, Mouret-Reynier MA, Durando X, Barthomeuf C, Chollet P. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther. 2010 Jan;9(1):8-14. Epub 2010 Jan 21. http://www.ncbi.nlm.nih.gov/pubmed/19901561

 

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