Chemoprevention

DEFINITION: Chemoprevention is a pharmacological approach to preventing cancer development using one or several natural or laboratory-made substancessuch as drugs, vitamins, dietary supplements, or foodsthat interfere with carcinogenesis.

Discussion: Cancer affects people of all ages in the United States. The incidence rates of some forms of cancer have declined over the past few years, while those of others have increased. Many financial and human resources have been spent on the diagnosis and treatment of cancer, and much research has been done on its prevention. Most of this research has confirmed that lifestyle choices play a significant role in cancer development. In fact, an estimated two-thirds of all cancers could be eliminated through healthy lifestyle choices. Changes in diet could eliminate almost one-third of cancers, while an exercise regimen would also be beneficial in this regard.

Prevention research has increasingly focused on chemoprevention for persons at high risk for certain cancers. These studies are designed to evaluate the effectiveness and usefulness of substances that may serve as chemoprevention. Since the 1980s, the National Cancer Institute has identified more than four hundred agents that may be able to prevent cancer. The value of these compounds in human subjects is the focus of numerous clinical trials.

How chemoprevention works: Research has focused on ways to arrest or even reverse the process of carcinogenesisthe transformation of normal living cells into abnormal or cancer cells. Studies show that certain substances can stop the formation of cancer tumors by one of two meanspreventing mutations (genetic, cellular changes) that often lead to cancer or stopping the duplication of damaged cells that can result in malignant tumors. Substances can interact at various points along the process of carcinogenesisthe beginning (initiation), middle (promotion), and end (progression). These substances may inactivate the cancer-causing agent, suppress tumor growth, induce beneficial enzymes, or act as antioxidants. Chemoprevention is the result of studies directed toward preventing cancer rather than its treatment.

An optimal chemoprevention agent should be nontoxic, safe for long-term use, easy to administer, inexpensive, and effective. Chemoprevention compounds may be natural dietary products or synthetic compounds.

Unlike chemotherapy, which kills normal healthy cells as well as cancer cells in people with active cancer, chemoprevention uses relatively harmless substances that may prevent cancer in people with no known malignancy but who are at increased risk for cancer development.

Examples of chemoprevention:Breast cancer is a primary concern for women in the United States. In 2024 the incidence rate for females was 133.8 cases per 100,000 people. The mortality rate was 18.7 per 100,000. Chemoprevention may be effective in preventing breast cancer in women who are at high risk or in preventing cancer in the second breast of women who have been previously diagnosed. Breast cancer prevention studies specifically target women who are cancer-free but at high risk. The National Cancer Institute (NCI) funded the Breast Cancer Prevention Trial (BCPT), with recruitment of subjects from 1992 through 1997. This study used the antiestrogen drug tamoxifen and had promising results, with 49 percent fewer diagnoses of invasive and noninvasive cancer in the group that took the drug. However, both temporary and some long-term adverse side effects, such as endometrial cancer, uterine sarcoma, pulmonary embolism, and deep vein thrombosis, occurred. Another study of breast cancer prevention in high-risk women compared outcomes using the chemoprevention drugs tamoxifen and raloxifene. Still, other National Cancer Institute clinical trials have begun investigating the effectiveness of soy protein, soy isoflavones, grape seed extract, and green tea extract in preventing breast cancer. Another possible chemoprevention for breast cancer is indole 3-carbinol from broccoli.

With the exception of skin cancer, prostate cancer is the most common cancer and is the second leading cause of cancer-related deaths in American men. The National Cancer Institute has several ongoing clinical trials assessing if certain antiandrogens and antiestrogens can prevent prostate cancer. One clinical trial used a drug called finasteride to reduce dihydrotestosterone (a metabolite of testosterone), associated with prostate cancerresults showed a reduction in the incidence of prostate cancer. However, there were side effects such as decreased libido (sexual drive), increased erectile dysfunction, and gynecomastia (excessive breast development in males). One study used pomegranate juice to slow or halt the increase in prostate-specific antigen (PSA)an increase in PSA would indicate that prostate cancer had returned. Another study employed a dietary approach to reduce fat intake and increase fruit and vegetable intake. Supplementation with vitamin E, selenium, or lycopene and nutritional substances such as tea, soy products, and indole-3-carbinol (in broccoli) may be chemoprotective. Still, these have not been proven effective at reducing the incidence of prostate cancer. Other subjects of clinical trials at the National Cancer Institute have included aspirin, fish oil, and lycopenefound in tomatoes, watermelon, and pink grapefruit.

Colorectal cancer is the third most common cancer in the United States and also ranks third in cancer-related deaths. Increased consumption of fruits and vegetables seems to provide some protection against colorectal cancer. The National Cancer Institute commits to develop and validate other possible ways to prevent colon cancer. One study involved the chemoprevention effect of calcium and vitamin D. Another study looked at consuming eicosapentaenoic acid (EPA), a highly purified form of omega-3 fatty acids naturally occurring in fish. A third study focused on the use of selenium, a naturally occurring micronutrient found in dietary sources such as nuts (especially Brazil nuts), meat, eggs, and fish. Several investigations have begun examining curcumin, part of a common spice used in Indian curries, for its antitumor and anti-inflammatory effects and its possible ability to prevent intestinal inflammation associated with colon cancer. Another topic of investigation has been the addition of high-fiber foods or wheat cereal to the diet to prevent colon cancer. Drugs that have begun to be studied regarding chemoprevention of colorectal cancer include aspirin, calcium carbonate, and 1α 25-dihydroxy cholecalciferol (active vitamin D3).

Cancer of the cervix (the organ that connects the vagina to the uterus) is a national concern. The American Cancer Society estimated that in 2024, 13,820 new cases are projected in the U.S. which will result in the deaths of 4,360 women. Research shows persistent exposure to the human papillomavirus (HPV) is a primary key to cervical cancer development. A 2021 study indicated 40% of the U.S. general population was affected by HPV. The rate of occurance was 41.8% of males and 38.3% of females. More than one hundred viruses are strains of HPV, and more than thirty of these are transmitted sexually. Some produce genital warts or benign tumors, and some place women at high risk for cervical cancer. In 2021, an estimated 37,000 new cancer cases were a result of HPV.

In 2006, the United States Food and Drug Administration approved new vaccines such as Gardasil that targeted the strains of HPV most commonly responsible for cervical cancer. A newer strain of Gardasil became available in 2018.

Vaccines given to young women before they become sexually active serve as chemoprevention for cervical cancer. Women may take the vaccines after they become sexually active, but they provide less protection because infection may already have occurred. As with all drugs, some side effects may occur. In 2024 the U.S. Center for Disease Control and Prevention provided new guidance on new HPV vaccine guidelines. The CDC identified three groups for HPV vaccinations. These included 15 years and younger, ages 15-45, and people with weaker immune responses. The schedule of dosages is different in each of the three categories.

Chemoprevention is being viewed as a key to cancer prevention in various other cancers. Researchers have begun testing whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent oral cancers. Some studies show that black raspberry extract may prohibit cancer growth in the mouth, as might Bowman-Birk inhibitor (BBI), a substance found in soybeans. The prevention of liver cancer, which kills 14,000 people annually, may be possible using oltipraz, a compound with properties resembling the antioxidant properties of broccoli, cabbage, and other cruciferous vegetables. Though liver cancer accounts for only about 2 percent of all cancers, the incidence is rising, and chemoprevention could slow this rate. The use of vaccines for the hepatitis B virus may protect against liver cancer.

Benefits and risks of chemoprevention: In 2021, almost 1.8 million people are diagnosed in the United States with new cases of cancer. This was 440.5 per 100,000 men and women. The goal of chemoprevention is to reduce the incidence of new cancers, which will improve the quality of life for many Americans and keep the workforce in place. In one study, cancer was associated with the highest loss of work days because of illness or impairment. The cost of cancer to the workers themselves and to their employers reinforces the need for measures and interventions such as chemoprevention to reduce the incidence of cancer.

Chemoprevention targets only high-risk populations because chemoprevention medications are not seen as useful or applicable for the general public. However, changes in diet and in the choice of foods consumed may affect the incidence of certain cancers. Most authorities do not recommend taking vitamins and supplements but rather endorse eating a well-balanced diet that is low in fat and high in fruits and vegetables. This is commonsense cancer prevention.

Successes are not seen quickly but rather may become visible over extended periods of time. In fact, one study, called the Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Study, demonstrated an 18 percent increase in lung cancer in the beta-carotene group. Clearly, judicious use of supplements is warranted because negative outcomes as well as positive ones can occur.

People who are considering a change in diet should check with their health care providers, as some vitamins and supplements can interact adversely with some prescription medications.

Summary: The research involving chemoprevention is encouraging and warrants more study and research dollars. Studies show that simple changes in lifestyle and eating habits can make a sizable impact on the incidence of cancer in the United States. Chemoprevention may some day be able to prevent people at high risk from developing cancer and keep cancer away in those who are in remission. The already burdened health care system could use its limited resources in trying to prevent other chronic diseases. Chemoprevention may not be the answer, but maybe it can be an answer to cancer in the United States.

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