Cancer secondary prevention
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Secondary Prevention
Chemoprevention
The concept that medications could be used to prevent cancer is an attractive one, and many high-quality clinical trials support the use of such chemoprevention in defined circumstances.
Daily use of tamoxifen, a selective estrogen receptor modulator (SERM), typically for 5 years, has been demonstrated to reduce the risk of developing breast cancer in high-risk women by about 50%. A recent study reported that the selective estrogen receptor modulator raloxifene has similar benefits to tamoxifen in preventing breast cancer in high-risk women, with a more favorable side effect profile.[1]
Raloxifene is a SERM like tamoxifen; it has been shown (in the STAR trial) to reduce the risk of breast cancer in high-risk women equally as well as tamoxifen. In this trial, which studied almost 20,000 women, raloxifene had fewer side effects than tamoxifen, though it did permit more DCIS to form.[1]
Finasteride, a 5-alpha-reductase inhibitor, has been shown to lower the risk of prostate cancer, though it seems to mostly prevent low-grade tumors.[2] The effect of COX-2 inhibitors such as rofecoxib and celecoxib upon the risk of colon polyps have been studied in familial adenomatous polyposis patients[3] and in the general population.[4][5] In both groups, there were significant reductions in colon polyp incidence, but this came at the price of increased cardiovascular toxicity.
Diet
A 2005 secondary prevention study showed that consumption of a plant-based diet and lifestyle changes resulted in a reduction in cancer markers in a group of men with prostate cancer who were using no conventional treatments at the time.[6] These results were amplified by a 2006 study in which over 2,400 women were studied, half randomly assigned to a normal diet, the other half assigned to a diet containing less than 20% calories from fat. The women on the low fat diet were found to have a markedly lower risk of breast cancer recurrence, in the interim report of December, 2006.[7]
Vitamins
There is a concept that cancer can be prevented through vitamin supplementation stems from early observations correlating human disease with vitamin deficiency, such as pernicious anemia with vitamin B12 deficiency, and scurvy with Vitamin C deficiency. This has largely not been proven to be the case with cancer, and vitamin supplementation is largely not proving effective in preventing cancer. The cancer-fighting components of food are also proving to be more numerous and varied than previously understood, so patients are increasingly being advised to consume fresh, unprocessed fruits and vegetables for maximal health benefits.[8]
The Canadian Cancer Society has advised Canadians that the intake of vitamin D has shown a reduction of cancers by close to 60%,[9] and at least one study has shown a specific benefit for this vitamin in preventing colon cancer.[10]
Vitamin D and its protective effect against cancer has been contrasted with the risk of malignancy from sun exposure. Since exposure to the sun enhances natural human production of vitamin D, some cancer researchers have argued that the potential deleterious malignant effects of sun exposure are far outweighed by the cancer-preventing effects of extra vitamin D synthesis in sun-exposed skin. In 2002, Dr. William B. Grant claimed that 23,800 premature cancer deaths occur in the US annually due to insufficient UVB exposure (apparently via vitamin D deficiency).[11] This is higher than 8,800 deaths occurred from melanoma or squamous cell carcinoma, so the overall effect of sun exposure might be beneficial. Another research group[12][13] estimates that 50,000–63,000 individuals in the United States and 19,000 - 25,000 in the UK die prematurely from cancer annually due to insufficient vitamin D.
The case of beta-carotene provides an example of the importance of randomized clinical trials. Epidemiologists studying both diet and serum levels observed that high levels of beta-carotene, a precursor to vitamin A, were associated with a protective effect, reducing the risk of cancer. This effect was particularly strong in lung cancer. This hypothesis led to a series of large randomized clinical trials conducted in both Finland and the United States (CARET study) during the 1980s and 1990s. This study provided about 80,000 smokers or former smokers with daily supplements of beta-carotene or placebos. Contrary to expectation, these tests found no benefit of beta-carotene supplementation in reducing lung cancer incidence and mortality. In fact, the risk of lung cancer was slightly, but not significantly, increased by beta-carotene, leading to an early termination of the study.[14]
Results reported in the Journal of the American Medical Association (JAMA) in 2007 indicate that folic acid supplementation is not effective in preventing colon cancer, and folate consumers may be more likely to form colon polyps.[15]
Genetic Testing
Genetic testing for high-risk individuals is already available for certain cancer-related genetic mutations. Carriers of genetic mutations that increase risk for cancer incidence can undergo enhanced surveillance, chemoprevention, or risk-reducing surgery. Early identification of inherited genetic risk for cancer, along with cancer-preventing interventions such as surgery or enhanced surveillance, can be lifesaving for high-risk individuals.
| Gene | Cancer types | Availability |
|---|---|---|
| BRCA1, BRCA2 | Breast, ovarian, pancreatic | Commercially available for clinical specimens |
| MLH1, MSH2, MSH6, PMS1, PMS2 | Colon, uterine, small bowel, stomach, urinary tract | Commercially available for clinical specimens |
References
- ↑ 1.0 1.1 Vogel V, Costantino J, Wickerham D, Cronin W, Cecchini R, Atkins J, Bevers T, Fehrenbacher L, Pajon E, Wade J, Robidoux A, Margolese R, James J, Lippman S, Runowicz C, Ganz P, Reis S, McCaskill-Stevens W, Ford L, Jordan V, Wolmark N (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. PMID 16754727.
- ↑ Thompson I, Goodman P, Tangen C, Lucia M, Miller G, Ford L, Lieber M, Cespedes R, Atkins J, Lippman S, Carlin S, Ryan A, Szczepanek C, Crowley J, Coltman C (2003). "The influence of finasteride on the development of prostate cancer". N Engl J Med. 349 (3): 215–24. PMID 12824459.
- ↑ Hallak A, Alon-Baron L, Shamir R, Moshkowitz M, Bulvik B, Brazowski E, Halpern Z, Arber N (2003). "Rofecoxib reduces polyp recurrence in familial polyposis". Dig Dis Sci. 48 (10): 1998–2002. PMID 14627347.
- ↑ Baron J, Sandler R, Bresalier R, Quan H, Riddell R, Lanas A, Bolognese J, Oxenius B, Horgan K, Loftus S, Morton D (2006). "A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas". Gastroenterology. 131 (6): 1674–82. PMID 17087947.
- ↑ Bertagnolli M, Eagle C, Zauber A, Redston M, Solomon S, Kim K, Tang J, Rosenstein R, Wittes J, Corle D, Hess T, Woloj G, Boisserie F, Anderson W, Viner J, Bagheri D, Burn J, Chung D, Dewar T, Foley T, Hoffman N, Macrae F, Pruitt R, Saltzman J, Salzberg B, Sylwestrowicz T, Gordon G, Hawk E (2006). "Celecoxib for the prevention of sporadic colorectal adenomas". N Engl J Med. 355 (9): 873–84. PMID 16943400.
- ↑ Ornish D; et al. (2005). "Intensive lifestyle changes may affect the progression of prostate cancer". The Journal of Urology. 174 (3): 1065–9, discussion 1069-70. PMID 16094059.
- ↑ Chlebowski RT, Blackburn GL, Thomson CA; et al. (2006). "Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study". J. Natl. Cancer Inst. 98 (24): 1767–76. doi:10.1093/jnci/djj494. PMID 17179478.
- ↑ The Omnivore's Dilemma, Andrew Pollan
- ↑ "Take vitamin D to reduce cancer risk, Canadian Cancer Society advises". Retrieved 2007-07-27.
- ↑ "Vitamin D Has Role in Colon Cancer Prevention". Retrieved 2007-07-27.
- ↑ "www3.interscience.wiley.com/cgi-bin/abstract/91016211/ABSTRACT?CRETRY=1&SRETRY=0". Retrieved 2007-07-27.
- ↑ "cat.inist.fr/?aModele=afficheN&cpsidt=17357586". Retrieved 2007-07-27.
- ↑ Grant WB, Garland CF, Holick MF. Comparisons of estimated economic burdens due to insufficient solar ultraviolet irradiance and vitamin D and excess solar UV irradiance for the United States. Photochem Photobiol. 2005 Nov-Dec;81(6):1276-86.
- ↑ National Cancer Institute Questions and Answers About Beta Carotene Chemoprevention Trials U.S. National Institutes of Health
- ↑ Cole BF, Baron JA, Sandler RS; et al. (2007). "Folic acid for the prevention of colorectal adenomas: a randomized clinical trial". JAMA. 297 (21): 2351–9. doi:10.1001/jama.297.21.2351. PMID 17551129.