Globally, breast cancer incidence continues to rise. At this time, our attention needs to turn to prevention. By preventing breast cancer, we can save lives and spare patients and their loved ones the trauma of a breast cancer diagnosis and debilitating treatment. Can this be done? In our generation we have witnessed the development of vaccines that have eliminated dreaded diseases like polio, and there is reason to expect that in the near future, we will see the elimination
of cervical cancer. Key to this success was the identification of causative agents.
Although breast cancer may have multiple causes, we have made huge strides in identifying the genes that are responsible for breast cancer. It is now time to build on this scientific progress, achieved largely at Johns Hopkins, to focus our attention to eradicating breast cancer through prevention.
Hormone Replacement Therapy
Hormone replacement therapy during menopause was widely used to reduce menopausal symptoms and prevent heart disease in women. However, clinical trials conducted in the 1990s found that it increased breast cancer but, unexpectedly, did not reduce heart disease. As a result, hormone replacement therapy has been much less frequently used and breast cancer incidence has dropped.
Early onset of menstruation and age at first pregnancy
Women who start menstruating early and women who have their first pregnancy after 30 are at higher risk. Since 1964, there has been an increase in the frequency of early menstruation and late first pregnancies among girls and women.
Obesity is on the rise in in the United States and studies have shown it is a risk factor for developing breast cancer. Even the foods we eat, such as canned meat and red meat may contribute to breast cancer risk.
In approximately 5-10% of patients, breast cancer results from a single gene mutation inherited from a parent. The two most common genes affected are BRCA 1 and BRCA 2. Not all carriers of these mutations develop breast cancer, but more than half do. If a woman has a BRCA 1 or BRCA 2 mutation, their probable risk is high enough to warrant treatment and/or close monitoring by a physician. Most women with breast cancer do not have any known risk factors for breast cancer. Johns Hopkins breast cancer experts are studying risk factors that may impact risk for developing the disease or its recurrence.
Prevention Research: What causes breast cancer?
Kala Visvanathan, M.D., M.H.S.
Johns Hopkins researchers are actively investigating risk factors for breast cancer and how to lower them. Dr. Kala Visvanathan, a cancer epidemiologist with appointments at Hopkins' Kimmel Cancer Center and Bloomberg School of Public Health, is highly interested in early detection and prevention of breast and ovarian cancers both in general and high-risk populations. She is conducting several studies evaluating both inherited risks for cancer along with environmental factors to determine who is likely to develop cancer and help women understand and change their cancer risk.
We need to do a better job of ensuring that all women have their breast cancer risk assessed and are informed about preventive options available to them, says Visvanathan, who co-directs a clinic for women at high risk of developing breast and ovarian cancers. Women who have a family history of breast cancer or have family members who developed breast cancer at a young age may benefit from genetic testing, more tailored screening and prevention plans, and chemoprevention medications used to help prevent cancer development.
Most breast cancers are caused by cellular alterations that acquire over time; identifying ways to interfere with these cancer-causing alterations is the focus of much of her work. Visvanathan is a leading expert in the study of biomarkers or cellular red flags that can warn of a patient's predisposition for developing cancer and serve as a target for prevention or therapy.
Ongoing breast cancer prevention research
Fighting the “fat” in cancer. Leptin, a hormone secreted by fat cells, is known to spur breast cancer growth and metastasis. Johns Hopkins investigators are testing ways to block leptin’s effect on breast cells. They are testing three bioactive food components on their ability to prevent breast cancer.
- To prevent cancer, go directly to the source. Breast tissue contains a vast network of ducts that act as tributaries delivering milk to the nipple. Most breast cancers develop in cells that coat the inner lining of these ducts, and targeting these cells with therapies may be a way to prevent the disease. Johns Hopkins experts have conducted early tests on patients showing that delivering chemotherapy through the nipple via tiny catheters is feasible. Their idea is to deliver high concentrations of therapies to the ducts, the cells that line the ducts, and breast tissue with minimal discomfort and little exposure to the rest of the body.
- Soy compound may strenghten breast cells against cancer. A nutrient called genistein, found in soybeans, may make breast cells more receptive to the cancer-prevention benefits of vitamin D. Work by Johns Hopkins researchers has shown that soy genistein reverses abnormal changes in the way proteins wrap around genes. These abnormal or “epigenetic” changes can push a breast cell’s fate more toward cancer. Reversing the epigenetic change can make cells sensitive to vitamin D, according to the investigators. They are identifying these changes in patients’ tissue samples, determining whether the changes pair with increased risk for breast cancer, such as hormonal factors, family history of breast cancer, and dense breast tissue. Their goal is to use epigenetic changes as a biomarker for women at increased risk for breast cancer and use medications or natural Kala Visvanathan products like soy genistein and vitamin D as a way to reduce risk.
- Preventing breast cancer from coming back. Breast cancer patients and those with pre-cancers are at higher risk of getting another breast cancer as compared with other women their age. Johns Hopkins investigators are studying whether drugs such as a cholesterollowering statin and bisphosphonate zoledronic acid, a drug that prevents bone loss in cancer patients, can reverse changes in breast tissue and prevent a second cancer in the unaffected breast.
- Safer Prevention Strategies. Prevention strategies sometimes have risks of their own. Women who have had had their ovaries removed for breast and ovarian cancer prevention are at risk for metabolic changes, cardiac disease, loss of bone density, and other cancers. Researchers are working to better understand and avert the side effects and
maximize the benefits.
- Biomarkers. Not everyone at risk will develop breast cancer. Many factors, including genetics, family history,a personal history of benign breast disease, and environmental exposures,play a role and are different for every woman. Laboratory research is leading us to biomarkers that will help us better identify and monitor women for biological changes indicative of cancer development so that we can individualize more aggressive preventive care to women who need it.
- Broccoli sprouts and other studies. Visvanathan is conducting a clinical trial of sulforaphane, a cancer-preventing compound found naturally in broccoli sprouts, to examine its effects on specific factors in breast tissue that are related to breast cancer risk and to assess whether sulforaphane increases the levels of protective enzymes in breast tissue For the study, women newly diagnosed with breast cancer are randomly assigned to take mango juice with broccoli sprout extract, or mango juice alone, prior to undergoing breast reduction surgery or mastectomy Dr. Visvanathan and colleagues will study patients blood and urine samples over a two-week period. Sulforaphane helps mobilize the body's cancer-fighting resources. In animal models, the compound has been shown to prevent breast cancer by turning on enzymes that protect cells. Read about Dr. Visvanathan's research from the Breast Center Matters newsletter.