Breast cancer primary prevention

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Jack Khouri

Overview

Prevention

Phytoestrogens and soy

Phytoestrogens such as found in soybeans have been extensively studied in animal and human in-vitro and epidemiological studies. The literature support the following conclusions:

  1. Plant estrogen intake, such as from soy products, in early adolescence may protect against breast cancer later in life.[1]
  2. Plant estrogen intake later in life is not likely to influence breast cancer incidence either positively or negatively.[2]

It seems reasonable to conclude that soybean-based phytoestrogens are not a major contributor to the incidence of breast cancer.

Folic acid (folate)

Studies have found that "folate intake counteracts breast cancer risk associated with alcohol consumption"[3] and "women who drink alcohol and have a high folate intake are not at increased risk of cancer."[4][5][6] A prospective study of over 17,000 women found that those who consume 40 grams of alcohol (about 3-4 drinks) per day have a higher risk of breast cancer. However, in women who take 200 micrograms of folate (folic acid or Vitamin B9) every day, the risk of breast cancer drops below that of alcohol abstainers.[7]

Folate is involved in the synthesis, repair, and functioning of DNA, the body’s genetic map, and a deficiency of folate may result in damage to DNA that may lead to cancer.[8] In addition to breast cancer, studies have also associated diets low in folate with increased risk of pancreatic, and colon cancer.[9][10]

Foods rich in folate include citrus fruits, citrus juices, dark green leafy vegetables (such as spinach), dried beans, and peas. Vitamin B9 can also be taken in a multivitamin pill.

Oophorectomy and mastectomy

Prophylactic oophorectomy (removal of ovaries), in high-risk individuals, when child-bearing is complete, reduces the risk of developing breast cancer by 60%, as well as reducing the risk of developing ovarian cancer by 96%.[11]

Bilateral prophylactic mastectomies have been shown to prevent breast cancer in high-risk individuals, such as patients with BRCA1 or BRCA2 gene mutations.

Medications

Hormonal therapy has been used for chemoprevention in individuals at high risk for breast cancer. In 2002, a clinical practice guideline by the US Preventive Services Task Force (USPSTF) recommended that "clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention" with a grade B recommendation.[12][13][14]

Selective estrogen receptor modulators (SERMs)

The guidelines were based on studies of SERMs from the MORE, BCPT P-1, and Italian trials. In the MORE trial, the relative risk reduction for raloxifene was 76%.[15] The P-1 preventative study demonstrated that tamoxifen can prevent breast cancer in high-risk individuals. The relative risk reduction was up to 50% of new breast cancers, though the cancers prevented were more likely estrogen-receptor positive (this is analogous to the effect of finasteride on the prevention of prostate cancer, in which only low-grade prostate cancers were prevented).[16][17] The Italian trial showed benefit from tamoxifen.[18]

Additional randomized controlled trials have been published since the guidelines. The IBIS trial found benefit from tamoxifen.[19] In 2006, the NSABP STAR trial demonstrated that raloxifene had equal efficacy in preventing breast cancer compared with tamoxifen, but that there were fewer side effects with raloxifene.[20] The RUTH Trial concluded that "benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke".[21] On September 14, 2007, Steven Galson, director, US Food and Drug Administration's Center for Drug Evaluation and Research announced approval of the sale of raloxifene to prevent invasive breast cancer in postmenopausal women.[22]

References

  1. Rice S, Whitehead SA (2006). "Phytoestrogens and breast cancer--promoters or protectors?". Endocr. Relat. Cancer. 13 (4): 995–1015. doi:10.1677/erc.1.01159. PMID 17158751.
  2. Gikas PD, Mokbel K. (2005Phytoestrogens and the risk of breast cancer: a review of the literature. Int J Fertil Women's Med.
  3. Mayo Clinic news release June 26 2001 "Folate Intake Counteracts Breast Cancer Risk Associated with Alcohol Consumption"
  4. Boston University,Folate, Alcohol, and Cancer Risk
  5. Bailey, L.B. Folate, methyl-related nutrients, alcohol and the MTHFR 677C -> T polymorphous affect cancer risk: intake recommendations. Journal of Nutrition, 2003, 133, 37485-37535
  6. Zhang S, Hunter D, Hankinson S, Giovannucci E, Rosner B, Colditz G, Speizer F, Willett W (1999). "A prospective study of folate intake and the risk of breast cancer". JAMA. 281 (17): 1632–7. PMID 10235158.
  7. Baglietto, Laura, et al. Does dietary folate intake modify effect of alcohol consumption on breast cancer risk? Prospective cohort study. British Medical Journal, August 8, 2005
  8. Jennings E. (1995). "Folic acid as a cancer preventing agent". Medical Hypotheses. 45 (3): 297–303. PMID 8569555.
  9. Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA, Speizer FE, Willett WC. (1998). "Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study". Annals of Internal Medicine. 129 (7): 517–524. PMID 9758570.
  10. name="Oldref_42">Freudenheim JL, Grahm S, Marshall JR, Haughey BP, Cholewinski S, Wilkinson G (1991). "Folate intake and carcinogenesis of the colon and rectum". International Journal of Epidemiology. 20 (2): 368–374. PMID 1917236.
  11. Kauff N, Satagopan J, Robson M, Scheuer L, Hensley M, Hudis C, Ellis N, Boyd J, Borgen P, Barakat R, Norton L, Castiel M, Nafa K, Offit K (2002). "Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation". N Engl J Med. 346 (21): 1609–15. PMID 12023992.
  12. "Guide to Clinical Preventive Services, Third Edition: Periodic Updates, 2000-2003". Agency for Healthcare Research and Quality. US Preventive Services Task Force. Retrieved 2007-10-07.
  13. "Chemoprevention of breast cancer: recommendations and rationale". Ann. Intern. Med. 137 (1): 56–8. 2002. PMID 12093249.
  14. Kinsinger LS, Harris R, Woolf SH, Sox HC, Lohr KN (2002). "Chemoprevention of breast cancer: a summary of the evidence for the U.S. Preventive Services Task Force". Ann. Intern. Med. 137 (1): 59–69. PMID 12093250.
  15. Cummings SR, Eckert S, Krueger KA; et al. (1999). "The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation". JAMA. 281 (23): 2189–97. PMID 10376571.
  16. Fisher B, Costantino JP, Wickerham DL; et al. (2005). "Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study". J. Natl. Cancer Inst. 97 (22): 1652–62. doi:10.1093/jnci/dji372. PMID 16288118.
  17. Fisher B, Costantino JP, Wickerham DL; et al. (1998). "Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study". J. Natl. Cancer Inst. 90 (18): 1371–88. PMID 9747868.
  18. Veronesi U, Maisonneuve P, Rotmensz N; et al. (2007). "Tamoxifen for the prevention of breast cancer: late results of the Italian Randomized Tamoxifen Prevention Trial among women with hysterectomy". J. Natl. Cancer Inst. 99 (9): 727–37. doi:10.1093/jnci/djk154. PMID 17470740.
  19. Cuzick J, Forbes JF, Sestak I; et al. (2007). "Long-term results of tamoxifen prophylaxis for breast cancer--96-month follow-up of the randomized IBIS-I trial". J. Natl. Cancer Inst. 99 (4): 272–82. doi:10.1093/jnci/djk049. PMID 17312304.
  20. Vogel VG, Costantino JP, Wickerham DL; et al. (2006). "Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial". JAMA. 295 (23): 2727–41. doi:10.1001/jama.295.23.joc60074. PMID 16754727.
  21. Barrett-Connor E, Mosca L, Collins P, et al Raloxifene Use for The Heart (RUTH) Trial Investigators. (2006). "Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women". N. Engl. J. Med. 355 (2): 125–37. doi:10.1056/NEJMoa062462. PMID 16837676.
  22. AFP.google.com, US approves Lilly's Evista for breast cancer prevention

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