CANCER PREVENTION

Dr.Azarm

INTRODUCTIONINTRODUCTION

Dr.Azarm

INTRODUCTIONINTRODUCTION Cancer deaths exceed seven million Cancer deaths exceed seven million worldwide each year, despite worldwide each year, despite overwhelming evidence that many overwhelming evidence that many malignancies are preventable malignancies are preventable nearly half a million people die from nearly half a million people die from cancer each year in the United States cancer each year in the United States (US) alone (US) alone It is estimated that 50 percent of It is estimated that 50 percent of cancer is preventable cancer is preventable

INTRODUCTIONINTRODUCTION risk factors (account for two-thirds of risk factors (account for two-thirds of all cancers in the US all cancers in the US

–tobacco use, tobacco use, –excess weight, excess weight, –poor diet, poor diet, –inactivityinactivity

Dr.Azarm

INTRODUCTIONINTRODUCTION nine modifiable risks were identified as the nine modifiable risks were identified as the cause of 35 percent of cancer deaths cause of 35 percent of cancer deaths worldwide: worldwide:

–smoking, smoking, –alcohol use, alcohol use, –diet low in fruit and vegetables, diet low in fruit and vegetables, –excess weight, excess weight, –inactivity, inactivity, –unsafe sex, unsafe sex, –urban air pollution, urban air pollution, –use of solid fuels, and use of solid fuels, and –contaminated injections in health-care settings contaminated injections in health-care settings

Harvard Report on Cancer Prevention

Volume 2: Prevention of

Human Cancer. Cancer Causes

and Control 1997; 8:S1.

INTRODUCTIONINTRODUCTIONLifestyle issues which promote Lifestyle issues which promote cancer are also risk factors for cancer are also risk factors for other diseases, such as stroke, other diseases, such as stroke, heart disease, and diabetes.heart disease, and diabetes.

Dr.Azarm

TOBACCO USETOBACCO USE –kills approximately 5 million people each kills approximately 5 million people each yearyear–mostly through mostly through

malignancy, malignancy, cardiovascular, andcardiovascular, andrespiratory diseaserespiratory disease

–Approximately one-half of all smokers die of Approximately one-half of all smokers die of a tobacco-related disease, and a tobacco-related disease, and –adult smokers lose an average of 13 years adult smokers lose an average of 13 years of life due to this addictionof life due to this addiction

TOBACCO USETOBACCO USE–Smoking is responsible for approximately 30 Smoking is responsible for approximately 30 percent of all cancer-related deaths in the US percent of all cancer-related deaths in the US –lung cancer, increasing risk 10 to 20-fold lung cancer, increasing risk 10 to 20-fold –causative factor for causative factor for

leukemia as well as cancers of leukemia as well as cancers of the oral cavity, the oral cavity, nasal cavity, nasal cavity, paranasal sinuses, paranasal sinuses, nasopharynx, nasopharynx, larynx, larynx, esophagus, esophagus, pancreas, liver, stomach, cervix, kidney, large bowel, pancreas, liver, stomach, cervix, kidney, large bowel, and bladder and bladder

TOBACCO USETOBACCO USE–smoking to more aggressive prostate smoking to more aggressive prostate cancerscancers –Smoking cessation leads to reduced risk of Smoking cessation leads to reduced risk of most tobacco-related diseases and a most tobacco-related diseases and a decrease in all cause mortality decrease in all cause mortality –The health benefits of quitting can be seen The health benefits of quitting can be seen at all ages and can be measured almost at all ages and can be measured almost immediately after cessation immediately after cessation

DIETDIET - -Dietary fatDietary fat –No clear link has been found between total fat No clear link has been found between total fat intake and colon or breast cancer but the data are intake and colon or breast cancer but the data are more convincing for prostate cancer and more convincing for prostate cancer and endometrial cancer endometrial cancer

–A diet high in animal fat may be an A diet high in animal fat may be an important factor in the development of important factor in the development of prostate cancer prostate cancer

intake of large amounts of alpha-linoleic acid intake of large amounts of alpha-linoleic acid and low amounts of linoleic acid appear to and low amounts of linoleic acid appear to increase risk increase risk serum levels of serum levels of testosterone are lower in men are lower in men who decrease their fat intake who decrease their fat intake

DIETDIET - -Red meatRed meat –elevate risk of colorectal cancer in both elevate risk of colorectal cancer in both men and women men and women –several factors have been suggested several factors have been suggested including heme content in the meat, animal including heme content in the meat, animal fat, and carcinogens produced when the fat, and carcinogens produced when the meat is cooked at high temperatures. meat is cooked at high temperatures.

DIETDIET - -Fruits and vegetablesFruits and vegetables –no association was seen between either no association was seen between either total or specific category of fruit and total or specific category of fruit and vegetable intake and colon cancer risk vegetable intake and colon cancer risk

TI

Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers.

AU

Michels KB; Edward Giovannucci; Joshipura KJ; Rosner BA; Stampfer MJ; Fuchs CS; Colditz GA; Speizer FE; Willett WC

SO

J Natl Cancer Inst 2000 Nov 1;92(21):1740-52.

DIETDIET - -Fruits and vegetablesFruits and vegetables

–Evidence is stronger for a link between Evidence is stronger for a link between prostate cancer and tomato products prostate cancer and tomato products –Lycopene, a carotenoid found in tomatoes, , a carotenoid found in tomatoes, has been postulated to be responsible for has been postulated to be responsible for this benefit but there are no data from well-this benefit but there are no data from well-designed clinical trials to support this designed clinical trials to support this hypothesis hypothesis T

IProspective study of fruit and vegetable consumption and incidence of colon and rectal cancers.

AU

Michels KB; Edward Giovannucci; Joshipura KJ; Rosner BA; Stampfer MJ; Fuchs CS; Colditz GA; Speizer FE; Willett WC

SO

J Natl Cancer Inst 2000 Nov 1;92(21):1740-52.

DIETDIET - -DairyDairy –relationship of dairy food intake and relationship of dairy food intake and ovarian cancer found no evidence of ovarian cancer found no evidence of association in case control studies association in case control studies – OTHER three prospective cohort studies OTHER three prospective cohort studies did demonstrate increased risk of ovarian did demonstrate increased risk of ovarian cancer with high intake of dairy foods cancer with high intake of dairy foods

DIETDIET - -FiberFiber –reduce the risk of heart disease [reduce the risk of heart disease [40,41] ] and diabetes [and diabetes [42,43], but its effect on ], but its effect on cancer risk reduction is less certain cancer risk reduction is less certain

DIETDIET - -Glycemic loadGlycemic load –Insulin and insulin-like growth factors Insulin and insulin-like growth factors promote cell proliferation, and it is promote cell proliferation, and it is hypothesized that hyperinsulinemia may hypothesized that hyperinsulinemia may promote certain cancers promote certain cancers

DIETDIET - -Omega-3 fatty acidsOmega-3 fatty acids –there is no association between omega-3 there is no association between omega-3 fatty acids and cancer risk for 11 different fatty acids and cancer risk for 11 different types of cancer types of cancer –Dietary supplementation with omega-3 Dietary supplementation with omega-3 fatty acids is unlikely to prevent cancer. fatty acids is unlikely to prevent cancer.

TI

Effects of omega-3 fatty acids on cancer risk: a systematic review.

AU

MacLean CH; Newberry SJ; Mojica WA; Khanna P; Issa AM; Suttorp MJ; Lim YW; Traina SB; Hilton L; Garland R; Morton SC

SO

JAMA. 2006 Jan 25;295(4):403-15.

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS –Several nutritional components have been Several nutritional components have been shown to affect cancer risk, but the role of shown to affect cancer risk, but the role of vitamins is less certain vitamins is less certain –neither neither vitamin C nor nor vitamin E supplementation was beneficial for supplementation was beneficial for prevention of the cancers evaluated prevention of the cancers evaluated

TI Antioxidants vitamin C and vitamin e for the prevention and treatment of cancer.

AU Coulter ID; Hardy ML; Morton SC; Hilton LG; Tu W; Valentine D; Shekelle PG

SO J Gen Intern Med. 2006 Jul;21(7):735-44.

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS –A 2006 National Institutes of Health (NIH) A 2006 National Institutes of Health (NIH) consensus conference panel concluded that consensus conference panel concluded that "present evidence is insufficient to "present evidence is insufficient to recommend either for or against the use of recommend either for or against the use of multivitamin supplements by the American multivitamin supplements by the American public to prevent chronic disease" public to prevent chronic disease"

TI Antioxidants vitamin C and vitamin e for the prevention and treatment of cancer.

AU Coulter ID; Hardy ML; Morton SC; Hilton LG; Tu W; Valentine D; Shekelle PG

SO J Gen Intern Med. 2006 Jul;21(7):735-44.

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS –It has not been proven that multivitamin It has not been proven that multivitamin and mineral supplements provide added and mineral supplements provide added benefit to a balanced, healthful diet benefit to a balanced, healthful diet

TI

The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference.

AU

Huang HY; Caballero B; Chang S; Alberg AJ; Semba RD; Schneyer CR; Wilson RF; Cheng TY; Vassy J; Prokopowicz G; Barnes GJ 2nd; Bass EB

SO

Ann Intern Med. 2006 Sep 5;145(5):372-85. Epub 2006 Jul 31.

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS - -Vitamin DVitamin D –may reduce the risk of colon cancermay reduce the risk of colon cancer–Direct effects of vitamin D on colonic Direct effects of vitamin D on colonic epithelial cells have been described epithelial cells have been described –Vitamin D may also decrease cancer risk Vitamin D may also decrease cancer risk through improved calcium absorption through improved calcium absorption –prostate cancer prostate cancer did not demonstrate a did not demonstrate a relationship relationship –breast cancer breast cancer may have a protective may have a protective effect effect

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS - -Vitamin DVitamin D in men was seen with an increment of in men was seen with an increment of 25 nmol/L in predicted 25(OH)D level in 25 nmol/L in predicted 25(OH)D level in data derived from the US Health data derived from the US Health Professionals Follow-Up Study Professionals Follow-Up Study This incremental level of serum This incremental level of serum 25(OH)D is not readily achieved with 25(OH)D is not readily achieved with diet (one glass of milk would be diet (one glass of milk would be predicted to increase the plasma level predicted to increase the plasma level only by 2 to 3 nmol/L), and would only by 2 to 3 nmol/L), and would require supplementation with at least require supplementation with at least 1500 IU vitamin daily 1500 IU vitamin daily

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS - -Vitamin DVitamin D

The authors raise a question whether The authors raise a question whether limiting sun exposure, to decrease skin limiting sun exposure, to decrease skin cancer risk, might increase the mortality cancer risk, might increase the mortality risk for other cancers. risk for other cancers.

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS - -CalciumCalcium –Increased calcium intake Increased calcium intake

reduced risk of colorectal cancer reduced risk of colorectal cancer increased risk of prostate cancer increased risk of prostate cancer

–700 mg/day700 mg/day protection against colorectal cancer protection against colorectal cancer without significantly increasing prostate without significantly increasing prostate cancer risk. cancer risk.

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS - -CalciumCalcium –Calcium Calcium

in the colonin the colon–may offer protection bymay offer protection by

DirectlyDirectly reducing epithelial cell proliferation, reducing epithelial cell proliferation,IndirectlyIndirectly by binding secondary bile acids and by binding secondary bile acids and ionized fatty acids ionized fatty acids

–total calcium over 2000 mg/day from both total calcium over 2000 mg/day from both diet and supplementation was linked to a diet and supplementation was linked to a 20 percent increase in 20 percent increase in prostate cancer risk prostate cancer risk

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS - -SeleniumSelenium –higher intake of higher intake of selenium decreases the decreases the risk of a variety of tumors risk of a variety of tumors –significant mortality reduction in cancers significant mortality reduction in cancers of of

lung lung coloncolonprostate prostate

–Selenium and Selenium and Vitamin E Cancer Prevention Cancer Prevention Trial (SELECT) will provide valuable Trial (SELECT) will provide valuable information on the overall risks and benefits information on the overall risks and benefits of selenium of selenium

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS - -FolateFolate a decrease in breast and colon cancer risk, a decrease in breast and colon cancer risk, especially in individuals who consume alcohol especially in individuals who consume alcohol supplementation with a multivitamin supplementation with a multivitamin containing folic acid provided even greater containing folic acid provided even greater benefit benefit increased dietary folate and increased dietary folate and vitamin B6 intake lowered colorectal cancer risk intake lowered colorectal cancer risk reduced risk for pancreatic cancer reduced risk for pancreatic cancer studies did not demonstrate an association studies did not demonstrate an association between low dietary intake of folate and between low dietary intake of folate and breast cancer breast cancer

DIETDIET - -VITAMINS AND NUTRIENTSVITAMINS AND NUTRIENTS - -other vitamin other vitamin supplementssupplements

Vitamin E (600 IU alpha-tocopherol every (600 IU alpha-tocopherol every other day) other day)

–did not prevent invasive cancer in a 10 year did not prevent invasive cancer in a 10 year follow-up to the Women's Health Study, follow-up to the Women's Health Study, evaluating healthy women age 45 years and evaluating healthy women age 45 years and older (mean age 55 years)older (mean age 55 years)

–One study did find a decrease in risk for One study did find a decrease in risk for prostate cancer with vitamin E prostate cancer with vitamin E supplementation in male smokers supplementation in male smokers


Beta carotene –may increase the incidence of lung cancer may increase the incidence of lung cancer incidence and mortality in patients with risk incidence and mortality in patients with risk factors (smokers or asbestos exposure) factors (smokers or asbestos exposure) –Beta carotene did not decrease cancer Beta carotene did not decrease cancer incidence in studies of American women [incidence in studies of American women [110] and men ] and men


Beta carotene –in rural China with baseline deficiencies in in rural China with baseline deficiencies in micronutrients micronutrients

a combination of a combination of beta-carotene, , selenium, and , and zinc zinc

–decreased the incidence of noncardia stomach decreased the incidence of noncardia stomach cancer, cancer, –but not other intestinal malignancies but not other intestinal malignancies

ALCOHOLALCOHOL –increases the risk of cancers of increases the risk of cancers of

colon, colon, breast breast OropharynxOropharynxesophagus esophagus

–Moderate alcohol use Moderate alcohol use has beneficial effects on cardiovascular health, has beneficial effects on cardiovascular health, consumption of as little as one drink per day consumption of as little as one drink per day has been associated with an increase cancer has been associated with an increase cancer risk risk

ALCOHOLALCOHOL mechanisms mechanisms

–solvent properties may allow carcinogens solvent properties may allow carcinogens to penetrate cell membranes to penetrate cell membranes –increases estrogen levels increases estrogen levels –impacts folate metabolism impacts folate metabolism –act as an irritant, causing increased cell act as an irritant, causing increased cell production production –transporter carrying carcinogens transporter carrying carcinogens –as a prometabolite for identified as a prometabolite for identified carcinogens carcinogens

PHYSICAL INACTIVITYPHYSICAL INACTIVITY Decreased physical activity Decreased physical activity

increase the risk for cancer, increase the risk for cancer, in addition to multiple other diseases in addition to multiple other diseases

Over 60 percent of US adults are not Over 60 percent of US adults are not regularly active, regularly active,

including 25 percent who are almost including 25 percent who are almost entirely sedentary entirely sedentary sedentary lifestyle is associated with 5 sedentary lifestyle is associated with 5 percent of cancer deaths percent of cancer deaths

PHYSICAL INACTIVITYPHYSICAL INACTIVITY –Physical activity is associated with a Physical activity is associated with a decreased risk of colon and breast cancer decreased risk of colon and breast cancer –negative correlation between moderate to negative correlation between moderate to strenuous exercise and ER-negative, but not strenuous exercise and ER-negative, but not ER-positive, breast cancer ER-positive, breast cancer –activity offers some protection against activity offers some protection against endometrial and prostate cancer endometrial and prostate cancer –physical activity may reduce the risk of physical activity may reduce the risk of lung cancer lung cancer

PHYSICAL INACTIVITYPHYSICAL INACTIVITY the protective effect of activity goes the protective effect of activity goes beyond its impact on body weight beyond its impact on body weight

PHYSICAL INACTIVITYPHYSICAL INACTIVITY mechanisms mechanisms

–reduction in circulating levels of insulin, reduction in circulating levels of insulin, hormones, and other growth factors hormones, and other growth factors –impact on prostaglandin levels; improved impact on prostaglandin levels; improved immune function, and immune function, and –altered bile acid metabolism altered bile acid metabolism

PHYSICAL INACTIVITYPHYSICAL INACTIVITY Physical activity during certain periods Physical activity during certain periods of life, such as adolescence, may offer of life, such as adolescence, may offer additional protection against disease additional protection against disease The optimal duration, intensity, and The optimal duration, intensity, and frequency of physical activity that may frequency of physical activity that may afford cancer protection is unknown. afford cancer protection is unknown.

EXCESS WEIGHTEXCESS WEIGHT –65 percent of US adults are overweight 65 percent of US adults are overweight –over 30 percent are considered obese over 30 percent are considered obese

EXCESS WEIGHTEXCESS WEIGHT with an increase in the risk of multiple with an increase in the risk of multiple cancers including cancers including

–colorectal, colorectal, –postmenopausal breast, postmenopausal breast, –endometrial, renal, and endometrial, renal, and –esophageal cancer, with esophageal cancer, with

a population attributable risk from a population attributable risk from –9 percent (postmenopausal breast cancer) 9 percent (postmenopausal breast cancer) –to 39 percent (endometrial cancer) to 39 percent (endometrial cancer)

EXCESS WEIGHTEXCESS WEIGHT Obesity may also increase risk for cancer ofObesity may also increase risk for cancer of

–prostate, prostate, –liver, liver, –gallbladder, gallbladder, –pancreas, pancreas, –stomach, stomach, –ovary, and ovary, and –cervix cervix –non-Hodgkin's lymphoma non-Hodgkin's lymphoma –multiple myeloma multiple myeloma

EXCESS WEIGHTEXCESS WEIGHT obesity in the US may account for obesity in the US may account for

–14 percent of cancer deaths in men and 14 percent of cancer deaths in men and –20 percent of cancer deaths in women 20 percent of cancer deaths in women

EXCESS SUN EXPOSUREEXCESS SUN EXPOSURE –Over 1 million cases of skin cancer, Over 1 million cases of skin cancer, including basal cell and squamous cell including basal cell and squamous cell carcinoma, are diagnosed each year carcinoma, are diagnosed each year –over 59,000 cases of malignant melanoma over 59,000 cases of malignant melanoma in the US in 2005 [in the US in 2005 [9], and the incidence ], and the incidence continues to rise continues to rise –most skin cancers are curable most skin cancers are curable –Radiation from the sun is the primary Radiation from the sun is the primary cause cause

both melanomatous and non-melanomatous both melanomatous and non-melanomatous skin cancer. skin cancer.

EXCESS SUN EXPOSUREEXCESS SUN EXPOSURE –correlate with total lifetime sun exposure correlate with total lifetime sun exposure –Cumulative sun exposure may also Cumulative sun exposure may also increase melanoma risk increase melanoma risk –repeated intense exposures leading to repeated intense exposures leading to blistering burns may be even more blistering burns may be even more dangerous dangerous

EXCESS SUN EXPOSUREEXCESS SUN EXPOSURE Recommendations for sun Recommendations for sun protectionprotection

–All individuals should limit the time spent All individuals should limit the time spent in the sun, in the sun,

especially between the hours of 10 am and 3 especially between the hours of 10 am and 3 pm, pm,

–wear hats, sunglasses, and other wear hats, sunglasses, and other protective clothing, protective clothing, –use sunscreen use sunscreen

EXCESS SUN EXPOSUREEXCESS SUN EXPOSURE Recommendations for sun Recommendations for sun protectionprotection

–majority of lifetime sun exposure usually majority of lifetime sun exposure usually occurs during childhood and adolescence occurs during childhood and adolescence –protective behaviors early in life will protective behaviors early in life will provide the greatest benefit provide the greatest benefit –Organization recently recommended Organization recently recommended against tanning bed use by anyone under against tanning bed use by anyone under the age of 18 the age of 18

INFECTIONINFECTION –17 percent of all new cancers worldwide 17 percent of all new cancers worldwide are due to infections are due to infections –Viruses may increase cancer risk through Viruses may increase cancer risk through

cellular transformation, cellular transformation, disruption of cell cycle control,disruption of cell cycle control,increased cell turnover rates, increased cell turnover rates, immune suppression immune suppression

INFECTIONINFECTION Human papillomavirus (HPV) with cervical and other Human papillomavirus (HPV) with cervical and other anogenital cancers [anogenital cancers [140] ] Hepatitis B (HBV) and C (HCV) with hepatocellular Hepatitis B (HBV) and C (HCV) with hepatocellular carcinoma [carcinoma [141] ] Human T-cell lymphotropic virus (HTLV-I) with adult T Human T-cell lymphotropic virus (HTLV-I) with adult T cell leukemia [cell leukemia [142] ] Human immunodeficiency virus (HIV-I) with Kaposi Human immunodeficiency virus (HIV-I) with Kaposi sarcoma and non-Hodgkin's lymphoma [sarcoma and non-Hodgkin's lymphoma [9] ] Human herpes virus 8 (HHV-8) with Kaposi sarcoma Human herpes virus 8 (HHV-8) with Kaposi sarcoma and primary effusion lymphoma [and primary effusion lymphoma [143,144] ] Epstein-Barr virus (EBV) with Burkitt's lymphoma [Epstein-Barr virus (EBV) with Burkitt's lymphoma [143] ] Helicobacter pylori (H. pylori) with gastric Helicobacter pylori (H. pylori) with gastric cancer cancer

INFECTIONINFECTION –The majority of these viruses are spread The majority of these viruses are spread through contact with infected blood or body through contact with infected blood or body fluids fluids –Vaccinations for HBV and HPV are Vaccinations for HBV and HPV are particularly promising particularly promising –Excess alcohol use may play a role in Excess alcohol use may play a role in cancer development in patients with cancer development in patients with chronic HBV and HCV infections and should chronic HBV and HCV infections and should be avoided be avoided –antiviral therapy may reduce the risk of antiviral therapy may reduce the risk of cancer cancer –Retroviral therapy for HIV infection reduce Retroviral therapy for HIV infection reduce the incidence of AIDS-related lymphoma the incidence of AIDS-related lymphoma

INFECTIONINFECTION –The majority of these viruses are spread The majority of these viruses are spread through contact with infected blood or body through contact with infected blood or body fluids fluids –Vaccinations for HBV and HPV are Vaccinations for HBV and HPV are particularly promising particularly promising –Excess alcohol use may play a role in Excess alcohol use may play a role in cancer development in patients with cancer development in patients with chronic HBV and HCV infections and should chronic HBV and HCV infections and should be avoided be avoided –antiviral therapy may reduce the risk of antiviral therapy may reduce the risk of cancer cancer –Retroviral therapy for HIV infection reduce Retroviral therapy for HIV infection reduce the incidence of AIDS-related lymphoma the incidence of AIDS-related lymphoma

CHEMOPREVENTIONCHEMOPREVENTION Selective estrogen receptor Selective estrogen receptor modulators and breast cancermodulators and breast cancer - -TamoxifenTamoxifen

–an estrogen receptor antagonist with both an estrogen receptor antagonist with both estrogen agonist and antagonist properties estrogen agonist and antagonist properties –It is approved in the US for both primary It is approved in the US for both primary and secondary prevention in high-risk and secondary prevention in high-risk women women

CHEMOPREVENTIONCHEMOPREVENTION Selective estrogen receptor Selective estrogen receptor modulators and breast cancermodulators and breast cancer - -TamoxifenTamoxifen

–Breast Cancer Prevention Trial (NSABP P-I), Breast Cancer Prevention Trial (NSABP P-I), –women at increased risk for breast cancer women at increased risk for breast cancer

age >60, age >60, history LCIS, history LCIS, calculated five year risk >1.66 percent calculated five year risk >1.66 percent according to the Gail model according to the Gail model

CHEMOPREVENTIONCHEMOPREVENTION Selective estrogen receptor modulators Selective estrogen receptor modulators and breast cancerand breast cancer - -TamoxifenTamoxifen

–an approximate 50 percent reduction in the an approximate 50 percent reduction in the relative risk of both invasive and noninvasive (ie, relative risk of both invasive and noninvasive (ie, ductal and lobular carcinomas in situ) breast ductal and lobular carcinomas in situ) breast cancer with tamoxifen. cancer with tamoxifen. –Risk was reduced only for estrogen receptor Risk was reduced only for estrogen receptor positive tumors. positive tumors. –Women in the tamoxifen arm had an Women in the tamoxifen arm had an approximately two-fold increased incidence in approximately two-fold increased incidence in endometrial tumors (cancers and uterine endometrial tumors (cancers and uterine sarcomas), pulmonary embolism, deep vein sarcomas), pulmonary embolism, deep vein thrombosis (DVT), and stroke thrombosis (DVT), and stroke

CHEMOPREVENTIONCHEMOPREVENTION Selective estrogen receptor Selective estrogen receptor modulators and breast cancermodulators and breast cancer - -TamoxifenTamoxifen Because of the potential for serious Because of the potential for serious side effects, the US Preventive Services side effects, the US Preventive Services Task Force (USPSTF) has recommended Task Force (USPSTF) has recommended againstagainst routine use of routine use of tamoxifen for for breast cancer prevention in women of breast cancer prevention in women of average risk. average risk.

CHEMOPREVENTIONCHEMOPREVENTION Selective estrogen receptor Selective estrogen receptor modulators and breast cancermodulators and breast cancer - -RaloxifeneRaloxifene

–— — Raloxifene is a selective estrogen is a selective estrogen receptor modulator (SERM) that is currently receptor modulator (SERM) that is currently approved for the prevention of approved for the prevention of osteoporosis, but not for the prevention of osteoporosis, but not for the prevention of breast cancer breast cancer –STAR trial suggest that raloxifene is as STAR trial suggest that raloxifene is as effective as effective as tamoxifen in reducing the in reducing the incidence of invasive breast cancers in incidence of invasive breast cancers in high-risk women, but with fewer of the high-risk women, but with fewer of the most serious side effects associated with most serious side effects associated with tamoxifen tamoxifen

CHEMOPREVENTIONCHEMOPREVENTION Selective estrogen receptor Selective estrogen receptor modulators and breast cancermodulators and breast cancer - -RaloxifeneRaloxifene

–There are no data on the use of raloxifene There are no data on the use of raloxifene in premenopausal women, and it should not in premenopausal women, and it should not be used in this group be used in this group

CHEMOPREVENTIONCHEMOPREVENTION Aspirin and other anti-inflammatory Aspirin and other anti-inflammatory drugsdrugs

–reducing colorectal cancer risk, reducing colorectal cancer risk, –and possibly effective for other cancers and possibly effective for other cancers –may cause cell cycle arrest or apoptosis may cause cell cycle arrest or apoptosis


–The optimal dose of aspirin, The optimal dose of aspirin, however has not been established [however has not been established [161]. ]. Low dose aspirin (100 mg every other day) did Low dose aspirin (100 mg every other day) did not prevent total cancer death, or incidence of not prevent total cancer death, or incidence of breast, colorectal, or lung cancer, when breast, colorectal, or lung cancer, when compared with placebo, at 10 year follow-up compared with placebo, at 10 year follow-up Full dose aspirin ( 325 mg) taken daily for a Full dose aspirin ( 325 mg) taken daily for a minimum of five years minimum of five years

–decrease the incidence of colorectal cancer in the decrease the incidence of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort Cancer Prevention Study II Nutrition Cohort


–There is good evidence that chronic use of There is good evidence that chronic use of aspirin, at doses suggested to decrease the aspirin, at doses suggested to decrease the incidence of colorectal cancer, incidence of colorectal cancer,

increases the risk for gastrointestinal bleeding increases the risk for gastrointestinal bleeding and hemorrhagic stroke and hemorrhagic stroke increases risk for renal failure and increases risk for renal failure and hypertension hypertension


–USPSTF and the American Cancer Society USPSTF and the American Cancer Society do not recommend aspirin or NSAID use to do not recommend aspirin or NSAID use to prevent colorectal cancer for average risk prevent colorectal cancer for average risk patients patients

CHEMOPREVENTIONCHEMOPREVENTION Finasteride and prostate cancerFinasteride and prostate cancer

–Compared to men in the placebo group, Compared to men in the placebo group, the incidence of prostate cancer was the incidence of prostate cancer was decreased in the finasteride group (18.4 percent decreased in the finasteride group (18.4 percent versus 24.4 percent)versus 24.4 percent) but there was an increase in the absolute but there was an increase in the absolute number and proportion of high grade tumors number and proportion of high grade tumors

CHEMOPREVENTIONCHEMOPREVENTION Finasteride and prostate cancerFinasteride and prostate cancer

–Concerns about increased risk for high Concerns about increased risk for high grade prostate cancer dampened grade prostate cancer dampened enthusiasm for the use of finasteride as a enthusiasm for the use of finasteride as a chemopreventive agent chemopreventive agent –It is premature to recommend the use of It is premature to recommend the use of finasteride as a chemopreventive agent in finasteride as a chemopreventive agent in men at high risk for prostate cancer, but men at high risk for prostate cancer, but clinicians should feel comfortable about clinicians should feel comfortable about using finasteride in men with large-gland using finasteride in men with large-gland BPH BPH

CHEMOPREVENTIONCHEMOPREVENTION SUMMARY AND SUMMARY AND RECOMMENDATIONSRECOMMENDATIONS

–Many cancers are preventable Many cancers are preventable –Basic lifestyle changes Basic lifestyle changes

have a tremendous impact on the rates of have a tremendous impact on the rates of cancer cancer also protect against other chronic diseases also protect against other chronic diseases (cardiovascular disease, stroke, and diabetes) (cardiovascular disease, stroke, and diabetes)

CHEMOPREVENTIONCHEMOPREVENTION General lifestyle recommendations include: General lifestyle recommendations include:

Avoid tobacco Avoid tobacco Be physically active Be physically active Maintain a healthy weight Maintain a healthy weight Eat a diet rich in fruits, vegetables, and Eat a diet rich in fruits, vegetables, and whole grains, and low in saturated/trans fat whole grains, and low in saturated/trans fat Limit alcohol Limit alcohol Protect against sexually transmitted Protect against sexually transmitted infections infections Avoid excess sun Avoid excess sun Get regular screening Get regular screening

CHEMOPREVENTIONCHEMOPREVENTION Specific factors associated with cancer risk Specific factors associated with cancer risk

include the following:include the following:– Tobacco use is responsible for 90 percent of all Tobacco use is responsible for 90 percent of all

lung cancer deaths, and is tied to multiple lung cancer deaths, and is tied to multiple other cancers other cancers

– The association of dietary fat, fruits, The association of dietary fat, fruits, vegetables, and fiber with cancer risk is largely vegetables, and fiber with cancer risk is largely unconfirmed. unconfirmed.

– Red meat consumption may promote colorectal Red meat consumption may promote colorectal cancer cancer

– high intake of tomatoes probably decreases high intake of tomatoes probably decreases prostate cancer risk. prostate cancer risk.

CHEMOPREVENTIONCHEMOPREVENTION Specific factors associated with cancer risk Specific factors associated with cancer risk

include the following:include the following:– Vitamin D may reduce the risk of colorectal and may reduce the risk of colorectal and

prostate cancer. prostate cancer. – Calcium intake, at a minimum of 700 mg/day, Calcium intake, at a minimum of 700 mg/day,

may protect against colorectal cancer may protect against colorectal cancer – but high calcium intake (>2000 mg/day) but high calcium intake (>2000 mg/day)

increases risk for prostate cancer.increases risk for prostate cancer.– Folic acid in diet has been associated with a in diet has been associated with a

decreased risk of colon and breast cancer, decreased risk of colon and breast cancer, especially in women who drink alcohol; especially in women who drink alcohol;

– data on multivitamin supplementation are data on multivitamin supplementation are inconsistent inconsistent

CHEMOPREVENTIONCHEMOPREVENTION Specific factors associated with Specific factors associated with

cancer risk include the following:cancer risk include the following:– Alcohol intake, even in moderate Alcohol intake, even in moderate

quantities, increases the risk for colon, quantities, increases the risk for colon, breast, esophageal and oropharyngeal breast, esophageal and oropharyngeal cancer. cancer.


cancer risk include the following:cancer risk include the following:– Physical activity is inversely related to Physical activity is inversely related to

risk for colon and breast cancer. risk for colon and breast cancer. – Excess weight increases the risk of Excess weight increases the risk of

multiple cancers. multiple cancers.


cancer risk include the following:cancer risk include the following:– Skin cancer is directly related to sun Skin cancer is directly related to sun

exposure, and melanoma rates are exposure, and melanoma rates are increasing. increasing.

– A history of blistering sunburns are of A history of blistering sunburns are of particular risk for melanoma; particular risk for melanoma;

– cumulative sun exposure has more cumulative sun exposure has more impact on non-melanoma cancers. impact on non-melanoma cancers.


cancer risk include the following:cancer risk include the following:– HPV, HCV, HTLV1, HIV, EBV, and H pylori HPV, HCV, HTLV1, HIV, EBV, and H pylori

have been linked to human cancers. have been linked to human cancers. – Exposure prevention, screening, and Exposure prevention, screening, and

early treatment for abnormal Pap smears early treatment for abnormal Pap smears and HIV infection can prevent cancer and HIV infection can prevent cancer


cancer risk include the following:cancer risk include the following:– Chemoprevention may be helpful in high Chemoprevention may be helpful in high

risk patients but risks and benefits risk patients but risks and benefits should be weighed carefully. should be weighed carefully. Aspirin and NSAIDs offer protection against and NSAIDs offer protection against

adenomatous polyps and colorectal cancer, adenomatous polyps and colorectal cancer, but are not recommended for routine use in but are not recommended for routine use in average risk patients. average risk patients.


cancer risk include the following:cancer risk include the following: Tamoxifen decreases incidence of breast decreases incidence of breast

cancer in high risk women, but increases the cancer in high risk women, but increases the risk for thromboembolic disease and early risk for thromboembolic disease and early stage endometrial cancer. stage endometrial cancer.

Raloxifene is a reasonable alternative, but is a reasonable alternative, but has not been evaluated in premenopausal has not been evaluated in premenopausal women women

The use of The use of finasteride as a chemopreventive as a chemopreventive agent should be discussed with men who are agent should be discussed with men who are interested in preventing prostate cancer interested in preventing prostate cancer

–What Is Cancer Screening?–Evaluation of a Screening Test–Breast Cancer Screening–Cervical Cancer Screening–Colorectal Cancer Screening–Skin Cancer Screening–Prostate Cancer Screening–Lung Cancer Screening–Adherence to Cancer Screening–Future of Screening

The goal of cancer screening The goal of cancer screening –detect cancer at an early stage when it is detect cancer at an early stage when it is treatable and curable treatable and curable

For a screening test to be useful:For a screening test to be useful:–the test or procedure should detect cancer the test or procedure should detect cancer earlier than would occur otherwise, earlier than would occur otherwise, –there should be evidence that earlier there should be evidence that earlier diagnosis results in improved outcomes diagnosis results in improved outcomes

Advances in genetics and molecular Advances in genetics and molecular biologybiology

–will make it possible to detect cancer at will make it possible to detect cancer at earlier and earlier stages along the earlier and earlier stages along the carcinogenesis pathway carcinogenesis pathway –the line between prevention and screening the line between prevention and screening may narrow further, as it has for colorectal may narrow further, as it has for colorectal and cervical cancers and cervical cancers

The National Cancer Policy Board The National Cancer Policy Board estimated that appropriate use of estimated that appropriate use of screening among screening among

–persons aged 50 and older could reduce persons aged 50 and older could reduce the mortality from colorectal cancer by 30% the mortality from colorectal cancer by 30% to 80%; to 80%; –women aged 50 and older could reduce women aged 50 and older could reduce mortality from breast cancer by 25% to mortality from breast cancer by 25% to 30%, 30%, –women aged 18 and older could reduce women aged 18 and older could reduce the rate of cervical cancer mortality by 20% the rate of cervical cancer mortality by 20% to 60%. to 60%.

What Is Cancer Screening?What Is Cancer Screening? lead to early detection of asymptomatic or lead to early detection of asymptomatic or unrecognized disease unrecognized disease acceptable acceptable inexpensive tests or examinations inexpensive tests or examinations in a large number of persons in a large number of persons expeditiously to separate apparently well expeditiously to separate apparently well persons who probably have disease from persons who probably have disease from those who probably do not. those who probably do not.

What Is Cancer Screening?What Is Cancer Screening? The main objective of cancer screening is to:The main objective of cancer screening is to:

– reduce morbidity and mortality from a particular reduce morbidity and mortality from a particular cancer among persons screened cancer among persons screened

What Is Cancer Screening?What Is Cancer Screening?

Characteristics of Screening Tests versus Diagnostic Tests

Screening Diagnosis

Applied to asymptomatic Applied to asymptomatic groupsgroups

Applied to symptomatic individuals

Lower cost per testLower cost per test Higher cost; all necessary tests applied to identify disease

Lower yield per testLower yield per test Higher probability of case detection

Lower adverse Lower adverse consequences of errorconsequences of error

Failure to identify true positives can delay treatment and worsen prognosis

What Is Cancer Screening?What Is Cancer Screening? cancers suitable for screening cancers suitable for screening

–High morbidity and mortality, High morbidity and mortality, –high prevalence in a detectable high prevalence in a detectable preclinical state,preclinical state,–possibility of effective and improved possibility of effective and improved treatment because of early detection, treatment because of early detection, and and –availability of a good screening test availability of a good screening test with high sensitivity and specificity, with high sensitivity and specificity, –low cost, and low cost, and –little inconvenience and discomfort little inconvenience and discomfort

What Is Cancer Screening?What Is Cancer Screening? cancers suitable for screening cancers suitable for screening

–Breast CABreast CA–Cervical CA Cervical CA –colorectal CAcolorectal CA

Evaluation of a Screening TestEvaluation of a Screening Test If the test is If the test is abnormalabnormal, ,

–what are the chances that disease is what are the chances that disease is present? present?

If the test result is If the test result is normalnormal, , –what are the chances that disease is what are the chances that disease is absent? absent?

Evaluation of a Screening TestEvaluation of a Screening Test The validity of a screening test The validity of a screening test

–SensitivitySensitivity and and specificityspecificity address the address the validity of screening tests validity of screening tests

Sensitivity is the probability of testing positive Sensitivity is the probability of testing positive if the disease is truly present. if the disease is truly present.

–As sensitivity increases, As sensitivity increases, false-negative decreases false-negative decreases Specificity is the probability of screening Specificity is the probability of screening negative if the disease is truly absent. negative if the disease is truly absent.

–A highly specific test A highly specific test false-positive decreases false-positive decreases

Evaluation of a Screening TestEvaluation of a Screening Test The validity of a screening test The validity of a screening test

–Predictive value Predictive value is a function of sensitivity, specificity, and is a function of sensitivity, specificity, and prevalence of disease prevalence of disease PV+ is an estimate of test accuracy in PV+ is an estimate of test accuracy in predicting presence of disease; predicting presence of disease; PV– is an estimate of the accuracy of the test PV– is an estimate of the accuracy of the test in predicting absence of disease in predicting absence of disease

Definitions of Criteria for Evaluating a Screening Test

Truth (Diagnostic Classification)

Screening Test Results Cancer Present Cancer Absent

Positive TP FP

Negative FN TN

Sensitivity = TP/TP + FN x 100

Specificity = TN/FP + TN x 100

PV+ = TP/TP + FP x 100

PV– = TN/TN + FN x 100

Accuracy = TP + TN/TP + TN + FP + FN x 100

FN, false-negative (number of subjects with cancer who are incorrectly classified as cancer-free by the test); FP, false-positive (number of cancer-free subjects who are incorrectly classified as having cancer by the test); PV, predictive value; TN, true-negative (number of cancer-free subjects who are correctly classified by the test); TP, true-positive (number of subjects with cancer who are correctly classified by the test).

Evaluation of a Screening TestEvaluation of a Screening Test Measures of Effectiveness Measures of Effectiveness

–Potential benefits include Potential benefits include improved prognosis for those with screen-improved prognosis for those with screen-detected cancers, detected cancers, the possibility of less radical treatment, the possibility of less radical treatment, reassurance for those with negative test reassurance for those with negative test results, results, resource savings if treatment costs are resource savings if treatment costs are reduced because of less radical treatments reduced because of less radical treatments


–The optimal outcome is a reduction in The optimal outcome is a reduction in cancer mortality cancer mortality


–Potential negative effects of screening Potential negative effects of screening includeinclude

physical, economic, and psychological physical, economic, and psychological consequences of false-positives and false-consequences of false-positives and false-negatives, negatives, the potential for overdiagnosis, the potential for overdiagnosis, the potential carcinogenic effects of screening,the potential carcinogenic effects of screening,the labeling phenomenon. the labeling phenomenon.


–Potential negative effects of screening Potential negative effects of screening includeinclude

physical, economic, and psychological physical, economic, and psychological consequences of false-positives and false-consequences of false-positives and false-negatives, negatives, the potential for overdiagnosis, the potential for overdiagnosis, the potential carcinogenic effects of screening,the potential carcinogenic effects of screening,the labeling phenomenon. the labeling phenomenon.


–Physicians should engage patients in Physicians should engage patients in discussions of the risks and benefits of discussions of the risks and benefits of cancer screening cancer screening

Table 22-5: Screening Guidelines for Breast, Colorectal, Prostate, and Cervical Cancers for Selected Health Care Organizations

Type of Cancer

American Cancer Society20 U.S. Preventive Services Task Force3 National Cancer Institute's Physician Data Query (PDQ) System1

Breast cancer

Annual mammography for women aged 40–69 y. No age cutoff. To the extent possible, a CBE should be performed at the time of mammography. Monthly BSE.136 Women aged 20–39 y should have a CBE from a health professional every 3 y and should perform BSE monthly.20

Recommends screening mammogram, with or without CBE, every 1–2 y.

Mammography every 1–2 y for women age 40 y and older. Women at higher risk should talk with their physicians about schedule.

Cervical cancer

For all women who are, or have been, sexually active or who have reached age 21 y, Pap test and pelvic examination yearly with Pap tests or every 3 y with liquid-based tests. At or after age 30 y, women who have had 3 normal tests can be screened every 2–3 y. Women with risk factors (e.g., HPV infection) may require more frequent screening. Screening is not necessary for women who have had total hysterectomies unless the surgery was for treatment of cervical cancer.

Pap test every 1–3 y for all women who are sexually active and/or have a cervix. No evidence to support an upper limit, but age 65 y can be defended in women with a history of normal and regular Pap tests.

Evidence strongly suggests a decrease in mortality for regular screening with Pap tests in women who are sexually active or who have reached age 18 y. The upper limit at which such screening ceases to be effective is unknown.

Colorectal cancer

One of the following schedules for men and women aged 50 y and over at average risk: FOBT yearly; sigmoidoscopy every 5 y; FOBT + sigmoidoscopy every 5 y; colonoscopy every 10 y; DCBE every 5 y. Those at high risk for colorectal cancer should begin screening earlier and/or more frequently.

Screening for colorectal cancer is strongly recommended for men and women aged 50 y and over. Several screening modalities are effective. Good evidence has been shown that periodic FOBT reduces mortality from colorectal cancer, and there is fair evidence that sigmoidoscopy alone or in combination with FOBT reduces mortality. No direct evidence has been shown for either colonoscopy or DCBE.

FOBT either annually or biennially using rehydrated or nonrehydrated stool specimens in people aged 50 y and over decreases mortality for colorectal cancer. Regular screening by sigmoidoscopy in people over age 50 y may decrease mortality from colorectal cancer. Evidence is insufficient to determine the optimal interval for such screening.

Prostate cancer

PSA test and DRE should be offered annually, beginning at age 50 y, to men who have a life expectancy of at least 10 y. Men at high risk for cancer should start screening at 45 y. Men should be given the information needed to make informed decisions about prostate cancer screening.

Evidence is insufficient to recommend for or against routine screening for prostate cancer using PSA testing or DRE.

Evidence is insufficient to establish that a decrease in mortality occurs with screening by DRE, transrectal ultrasound, or PSA.

Screening Guidelines for Breast, Colorectal, Prostate, and Cervical Cancers for Selected Health Care Organizations

Type of Cancer

American Cancer Society20

U.S. Preventive Services Task Force3

National Cancer Institute's Physician Data Query (PDQ) System1

Breast cancer

Annual mammography for women aged 40–69 y. No age cutoff. To the extent possible, a CBE should be performed at the time of mammography. Monthly BSE.136 Women aged 20–39 y should have a CBE from a health professional every 3 y and should perform BSE monthly.20

Recommends screening mammogram, with or without CBE, every 1–2 y.

Mammography every 1–2 y for women age 40 y and older. Women at higher risk should talk with their physicians about schedule.

Table 22-5: Screening Guidelines for Breast, Colorectal, Prostate, and Cervical Cancers for Selected Health Care Organizations

Type of Cancer




Cervical cancer

For all women who are, or have been, sexually active or who have reached age 21 y, Pap test and pelvic examination yearly with Pap tests or every 3 y with liquid-based tests. At or after age 30 y, women who have had 3 normal tests can be screened every 2–3 y. Women with risk factors (e.g., HPV infection) may require more frequent screening. Screening is not necessary for women who have had total hysterectomies unless the surgery was for treatment of cervical cancer.

Pap test every 1–3 y for all women who are sexually active and/or have a cervix. No evidence to support an upper limit, but age 65 y can be defended in women with a history of normal and regular Pap tests.

Evidence strongly suggests a decrease in mortality for regular screening with Pap tests in women who are sexually active or who have reached age 18 y. The upper limit at which such screening ceases to be effective is unknown.

Type of Cancer




Colorectal cancer

One of the following schedules for men and women aged 50 y and over at average risk: FOBT yearly; sigmoidoscopy every 5 y; FOBT + sigmoidoscopy every 5 y; colonoscopy every 10 y; DCBE every 5 y. Those at high risk for colorectal cancer should begin screening earlier and/or more frequently.

Screening for colorectal cancer is strongly recommended for men and women aged 50 y and over. Several screening modalities are effective. Good evidence has been shown that periodic FOBT reduces mortality from colorectal cancer, and there is fair evidence that sigmoidoscopy alone or in combination with FOBT reduces mortality. No direct evidence has been shown for either colonoscopy or DCBE.

FOBT either annually or biennially using rehydrated or nonrehydrated stool specimens in people aged 50 y and over decreases mortality for colorectal cancer. Regular screening by sigmoidoscopy in people over age 50 y may decrease mortality from colorectal cancer. Evidence is insufficient to determine the optimal interval for such screening.

Type of Cancer




Prostate cancer

PSA test and DRE should be offered annually, beginning at age 50 y, to men who have a life expectancy of at least 10 y. Men at high risk for cancer should start screening at 45 y. Men should be given the information needed to make informed decisions about prostate cancer screening.

Evidence is insufficient to recommend for or against routine screening for prostate cancer using PSA testing or DRE.

Evidence is insufficient to establish that a decrease in mortality occurs with screening by DRE, transrectal ultrasound, or PSA.

Breast Cancer ScreeningBreast Cancer Screening lifetime breast cancer incidence is lifetime breast cancer incidence is 7.8%, 7.8%, Widely accepted techniques for breast Widely accepted techniques for breast cancer screening, cancer screening,

–mammography,mammography,–clinical breast examination (CBE), and clinical breast examination (CBE), and –breast self-examination (BSE). breast self-examination (BSE).

–No cancer screening test has been studied more No cancer screening test has been studied more than mammography (with or without CBE). than mammography (with or without CBE).

Breast Cancer ScreeningBreast Cancer Screening Most trials have included women in Most trials have included women in their 40s, their 40s, two trials began accrual at age 45. two trials began accrual at age 45. One of the Canadian trials [the first One of the Canadian trials [the first National Breast Cancer Screening Study National Breast Cancer Screening Study (NBSS1)] was designed to examine (NBSS1)] was designed to examine mammography and CBE versus usual mammography and CBE versus usual care for women in their 40s care for women in their 40s

Breast Cancer ScreeningBreast Cancer Screening

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