Therese B. Bevers, M.D.
Professor, Clinical Cancer Prevention
Medical Director, Cancer Prevention Center
The University of Texas MD Anderson Cancer Center
Hi, I am Dr. Terry Bevers, Professor of Clinical Cancer Prevention and Medical Director of the Cancer Prevention Center at the University of Texas MD Anderson Cancer Center. Today, our talk is about Cancer Prevention: Part II.
In a previous lecture, you heard Sally Scroggs talk about lifestyle modifications for risk reduction. Today, the lecture will focus on understanding types of prophylactic surgical interventions used to prevent malignancies and identification of chemoprevention strategies for several common cancers.
I want to first focus on prophylactic surgical interventions. Surprisingly, there are a number of surgical interventions that can be used to reduce an individual's risk of developing cancer. Today, I would like to focus on prophylactic mastectomy and prophylactic salpingo-oophorectomy.
Prophylactic mastectomy is the removal of the breast tissue, both sides, to reduce a woman's risk of developing breast cancer. This strategy is highly effective for breast cancer risk reduction; reducing a woman's chance of developing the disease by about 90%. However, it does carry some significant risk associated with it. It alters a woman's body form permanently and her own self-image. It is irreversible. And for these reasons we typically only consider it in exceptional circumstances. Such circumstances would be a woman who is a gene mutation carrier for a BRCA1 or BRCA2 mutation. The risk is quite high carrying a 50% to 80% lifetime risk. Given this high lifetime risk, certainly, we would consider a very highly effective risk reduction strategy such as prophylactic mastectomy.
Another prophylactic surgical intervention is prophylactic oophorectomy or prophylactic salpingo-oophorectomy where the tubes and ovaries on both sides are removed. This not only reduces a woman's chance of developing ovarian cancer by about 85 to 96%, but also reduces a woman's chance of developing breast cancer if done early in her 30s or 40s. The breast cancer risk reduction can be as much as 47% to 68%. There are risks associated with this particular surgical intervention. It does cause premature menopause with all the associated systemic effects, such as increased risk of heart disease, increased risk of osteoporosis, and associated menopausal symptoms, such as hot flashes, night sweats, and the like. One study has shown that the use of postmenopausal hormone therapy does not appear to affect a woman's risk of developing breast cancer if she were to take it after a prophylactic oophorectomy.
Now, I want to switch our attention to chemoprevention, which is the use of medications to reduce an individual's risk of developing the disease, in this case, cancer.
There are a large number of medications or substances that are being explored to reduce the development of cancer. This list is just a partial list. Some such as SERMs, or Selective Estrogen Receptor Modulators, actually have FDA approval for their use to reduce the risk of developing breast cancer. Others are still under investigation. The proposed mechanisms are listed on this slide.
I want to briefly talk about two agents, tamoxifen and raloxifene, that have been shown to reduce the risk of developing breast cancer. These drugs reduce the risk of both invasive and noninvasive breast cancer by one-half. They also reduce the risk of developing osteoporotic-type bone fractures. There are, however, risks associated with both of these drugs. Raloxifene has fewer risks than tamoxifen, has fewer deep vein thromboses or DVTs, and fewer pulmonary embolus or PEs. It does not have the increased risk of endometrial cancer or cataracts that is seen with tamoxifen. The side effects in regards to hot flashes, vaginal dryness, and other annoying side effects are fairly comparable between the two drugs.
Women, who are at increased risk, have options now to reduce the risk of developing breast cancer. Premenopausal woman have the option of taking tamoxifen. Postmenopausal woman have the option of either tamoxifen for five years or raloxifene for lifelong use.
Turning our attention now to prostate cancer, we have a study that has looked at Proscar® or finasteride for the prevention of prostate cancer.
This study, called the Prostate Cancer Prevention Trial, actually showed that there were fewer cases of prostate cancer in the finasteride arm. In looking at 1000 men followed over seven years, taking either finasteride or no finasteride, there were actually 15 fewer cases of prostate cancer in the finasteride arm when compared to the no finasteride arm. However, somewhat surprisingly, four more cases of high-grade cancers were seen. It was this observation that has led to some reluctance in the use of finasteride generally for men to reduce the risk of developing prostate cancer.
Turning our attention now to some vaccines that can be beneficial in reducing individuals' risk of developing cancer.
I want to briefly talk about hepatitis B and the hepatitis B vaccine. We know that hepatitis B and hepatitis V --- hepatitis B and hepatitis C infections are major risk factors for the development of hepatocellular or liver carcinoma. In fact, the risk is even greater if there is infection with both hepatitis B and C. Chronic infections with these account for about 40% of cases of hepatocellular or liver cancer that are seen. It has been hypothesized that vaccination against hepatitis B may reduce the incidence of liver cancer by as much as one-half.
We have been using hepatitis B vaccine as part of the childhood immunization series for a number of years. Certainly, the individuals who routinely received hepatitis B vaccine are still under the age that we would normally expect to see liver cancer develop. So it will be a while before we begin to see the effects of hepatitis B vaccination on the population. There are, however, some high-risk adult populations that are listed here, and these populations should seriously be considered for hepatitis B vaccination to reduce the risk of being infected with hepatitis B and, thus, potentially reduce the risk of developing liver cancer.
Finally, I would like to talk about cervical cancer and HPV vaccine or human papillomavirus vaccine.
There are actually two different types of HPV vaccines that are now available on the market. Gardasil® is a quadrivalent vaccine, meaning it has four types of HPV included in the vaccine. It has two high-risk or oncogenic cancer causing types, which is HPV 16 and 18, and two low-risk types HPV 6 and 11. Cervarix® is a bivalent vaccine focusing only on the high-risk types, HPV 16 and 18. It has been found in studies that women who were immunized with HPV vaccine obtained nearly 100% prevention against the development of precancerous lesions caused by HPV 16 and 18. It is important to realize that HPV 16 and 18 account for about 70% of the cervical cancers that occur in the United States. Because Gardasil® also includes HPV 6 and 11 in the vaccine, it can prevent against the diseases that those are associated with, specifically genital warts. In fact, they are the cause of over 90% of genital warts. While these are not oncogenic or cancer-causing, certainly they can be problematic, and there is the potential to reduce the incidence of these developing.
HPV vaccine will not protect against HPV infection caused by other high-risk types, so we still continue to need --- we still need to screen women with the Pap smear because certainly they can have an HPV infection from other high-risk types that would lead to cervical dysplasia or cervical cancer. The vaccine does not treat an HPV infection. In fact, there is no treatment currently for HPV infections. It only prevents the infection from occurring. For that reason, to be most effective, the vaccine should be given prior to the initiation of sexual activity, as HPV is largely transmitted through sexual activity.
The current Centers for Disease Control recommendations for HPV vaccination are that females aged 11 to 12 should receive routine vaccination with a series of three vaccinations over a six-month interval. Females aged 13 through 26 may obtain vaccination as a catch-up mechanism, but they should also be counseled that, if they have become sexually active, they may have already been infected with one of the HPV types in the vaccine, and would not, thus, obtain protection against that particular HPV type. For that reason, they may have diminished benefits from the vaccination. HPV vaccination is not currently recommended for women under the age of 9 or over the age of 26, although studies are currently ongoing. Recently, there have been some new recommendations for Gardasil® vaccination in males to prevent the development and transmission of genital warts. Certainly, since Gardasil® vaccination would also prevent HPV infection with 16 and 18 in the males, it may help to decrease the transmission of these two HPV types to their sexual partners, thus potentially reducing the risk further for the population.
In conclusion, there are many primary prevention strategies that are available to reduce a person's risk of developing cancer. These include lifestyle modifications, that you heard Sally talk about, such as diet and exercise, avoidance of smoking, or smoking cessation if you already smoke, and excessive sun exposure. Also for those who are at increased risk of the disease, we have other options, such as prophylactic surgical interventions and chemoprevention. I hope that you have enjoyed this lecture and we welcome your feedback. Thank you.
Cancer Prevention: Part II video
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