Chapter 078. Prevention and Early Detection of Cancer (Part 5) Chemoprevention of Breast Cancer Hormonal manipulation is being tested in the primary prevention of breast cancer. Tamoxifen is an antiestrogen with partial estrogen agonistic activity in some tissues, such as endometrium and bone. One of its actions is to upregulate transforming growth factor β, which decreases breast cell proliferation. In randomized placebo-controlled trials to assess tamoxifen as adjuvant therapy for breast cancer, tamoxifen reduced the number of new breast cancers in the opposite breast by more than a third. In a randomized placebo-controlled prevention trial involving >13,000 women at high risk, tamoxifen decreased the risk of developing breast cancer by 49% (from 43.4 to 22.0 per 1000 women) after a median follow- up of nearly 6 years. The International Breast Cancer Intervention Study (IBIS-I) trial had similar findings. In both studies tamoxifen also reduced bone fractures; a small increase in risk of endometrial cancer, stroke, pulmonary emboli, and deep vein thrombosis was noted. Tamoxifen has been approved by the U.S. Food and Drug Administration for reduction of breast cancer in women at high risk for the disease (1.66% risk at 5 years based on the Gail risk model: http://www.nci.nih.gov/cancertopics/pdq/genetics/breast-and- ovarian/healthprofessional#Section_66). A trial comparing tamoxifen with another selective estrogen receptor modulator, raloxifene, showed that raloxifene is comparable to tamoxifen in cancer prevention. Raloxifene is associated with more noninvasive breast cancer than tamoxifen; the drugs are similar in risks of other cancers, fractures, ischemic heart disease, and stroke. Because the aromatase inhibitors are even more effective than tamoxifen in adjuvant breast cancer therapy, it is hoped that they also are more effective in breast cancer prevention. However, no data are available on this point. Chemoprevention of Prostate Cancer Finasteride is a 5-α-reductase inhibitor. It inhibits conversion of testosterone to dihydrotestosterone (DHT), a potent stimulator of prostate cell proliferation. The Prostate Cancer Prevention Trial randomly assigned men ≥55 years at average risk of prostate cancer to finasteride or placebo. After 7 years of therapy, the incidence of prostate cancer was 18.4% in the finasteride arm and 24.8% in the placebo arm, a statistically significant difference. However, the finasteride group had more patients with tumors of Gleason score 7 and higher compared to the placebo arm (6.4% vs 5.1%). The clinical significance of this finding, if any, is unknown. Selenium is being tested as a prostate cancer preventive based on laboratory studies, epidemiologic data, and a small randomized skin cancer prevention trial that showed a significantly decreased number of prostate cancers in men taking selenium. In the placebo group, 16 prostate cancers were diagnosed versus 4 in the treatment group among the 843 men who began the study with a serum prostate specific antigen level <4 ng/mL. The ATBC study cited above showed in secondary analysis that the risk of prostate cancer was reduced 33% in men taking α-tocopherol (99 cases in those on the drug; 151 cases on placebo). A prospective randomized trial to assess these drugs is ongoing. Vaccines and Cancer Prevention A number of infectious agents cause cancer. Hepatitis B and C are linked to liver cancer, some human papilloma virus (HPV) strains are linked to cervical and head and neck cancer, and Helicobacter pylori is associated with gastric cancer and lymphoma. Vaccines to protect against these agents may reduce the risk of their associated cancers. The hepatitis B vaccine is effective in preventing hepatitis and hepatomas due to chronic hepatitis B infection. Public health officials are encouraging widespread administration of the hepatitis B vaccine, especially in Asia, where the disease is epidemic. A four-valent HPV vaccine (Gardasil) is 100% effective at preventing infection with any of the four component strains (6, 11, 16, 18). The vaccine is recommended for girls and women ages 9–26 years. Reduction in these HPV types could prevent >70% of the cervical cancers worldwide. Surgical Prevention of Cancer Some organs in some individuals are at such high risk of developing cancer that surgical removal of the organ at risk is recommended. Women with severe cervical dysplasia are treated with conization and occasionally even hysterectomy. Colectomy is used to prevent colon cancer in patients with familial polyposis or ulcerative colitis. Prophylactic bilateral mastectomy is chosen for breast cancer prevention among women with genetic predisposition to breast cancer. In a prospective series of 139 women with BRCA1 and BRCA2 mutations, 76 chose to undergo prophylactic mastectomy and 63 chose close surveillance. At 3 years, no cases of breast cancer had been diagnosed in those opting for surgery, but eight in the surveillance group had developed breast cancer. A larger retrospective cohort study reported that prophylactic mastectomy could reduce risk of breast cancer by 90%. The effect of the procedure on mortality is unknown. Observational studies are prone to a variety of biases associated with the choice to undergo prophylactic surgery; thus, such studies can give an overestimate of the magnitude of benefit. Surgery is also used to manage hormonal cancers. Orchiectomy is an effective method of androgen deprivation in prostate cancer, and oophorectomy is effective in hormone-dependent breast cancer. . Chapter 078. Prevention and Early Detection of Cancer (Part 5) Chemoprevention of Breast Cancer Hormonal manipulation is being tested in the primary prevention of breast cancer. . Vaccines and Cancer Prevention A number of infectious agents cause cancer. Hepatitis B and C are linked to liver cancer, some human papilloma virus (HPV) strains are linked to cervical and head and. epidemiologic data, and a small randomized skin cancer prevention trial that showed a significantly decreased number of prostate cancers in men taking selenium. In the placebo group, 16 prostate cancers