Unraveling Breast Cancer

Few words strike as much fear among women as breast cancer. According to the National Cancer Institute, here in the United States an estimated 178,000 women each year are diagnosed with breast cancer and over 43,000 die. Breast cancer is “overwhelmingly the most common malignancy in women,” says Marc E. Lippman, M.D., Director of the Vincent T. Lombardi Cancer Center at Georgetown University Medical Center.

Although breast self-exam and regular mammograms are still vital to a women’s health regimen, discoveries in molecular biology are leading to new ways of detecting and treating breast cancer, as well as opening up promising avenues of prevention that may make a huge difference to millions of women. “We’re ushering in a new era,” says Dr. Lippman.

The Nina Hyde Breast Cancer Research Program—named in honor of the late Washington Post fashion editor who helped raise public awareness of the disease—is an integral part of the largest breast cancer program in the Washington area, and one of the largest in the world. Dr. Lippman, who led the breast cancer program at the National Cancer Institute, brought over 35 colleagues with him when recruited to the Lombardi Cancer Center in 1988.

Detection
“All breast cancer—indeed all cancer—is ultimately due to gene mutations that allow cellular division to run amok, causing cancerous cells to displace and invade normal tissue.” Dr. Lippman goes on to point out, “While all breast cancer is genetic in cause, only about 10 percent of cases are inherited. The remainder is due to spontaneous mutations that occur during a person’s life.”

In recent years, several genes have been identified that have been linked to “inherited” breast cancer. The two most common genes are known as BRCA-1 and BRCA-2. Today, the Lombardi Cancer Center offers the only genetic testing of BRCA-1 and BRCA-2 in the Washington area. This testing is available free to women who have a significant family history of breast or ovarian cancer.

Lombardi researchers have also pioneered a technique that analyzes genes from a single cell obtained from breast fluid. “Not many people know this, but you can get fluid from the breast even if a woman isn’t lactating,” explains Dr. Lippman. “We can find cancer cells shed in breast fluid long before they become invasive. This is very exciting technology.”

Improving Surgical Treatments
Surgery has traditionally been one of the primary treatments for breast cancer. Knowledge gained from clinical research has led to refinements in technique that make surgery less traumatic for patients. Many women with a family history of breast cancer who are at high risk opt for double mastectomy, which often reduces or eliminates their risk of developing the disease. Today, new hormone preventions can also reduce that risk nearly 50%.

Radical mastectomy has become less common over the last 20 years, in favor of newer, conservative surgical techniques that spare breast tissue. With mammography pinpointing cancer earlier, an increasing number of women are able to have a “lumpectomy.” Removing a minimum of breast tissue and done as relatively minor same-day surgery, a lumpectomy generally needs to be combined with breast irradiation.

Lymph nodes are vital to the immune system by acting as filters for lymph— a watery fluid that contains white blood cells and antibodies that continually wash through bodily tissues. With dye and radioisotope tracers, surgeons today are able to identify and biopsy the breasts’ “sentinel lymph node” or the draining nodal basin. This procedure offers the surgeon a precise location to detect if cancer has possibly spread to other areas within the body. The sentinel node biopsy is becoming the new standard for the staging of early malignant melanoma.

“With a favorable diagnosis from a sentinel node biopsy, we can avoid chemotherapy and problems caused by removing the lymph nodes, as well as reassure the patient,” says Dr. Lippman.

Other Treatments
New drugs that are more effective and less toxic are making their way from the laboratory to the patient’s bedside. The drug tamoxifen has been used for the last 20 years to treat patients with advanced breast cancer. Recently, it has been used as an additional therapy for early stage breast cancer. As part of the Breast Cancer Prevention Trial, Lombardi scientists recently confirmed use of tamoxifen to prevent development of breast cancer for high-risk women. Results of this study show an estimated reduction in diagnoses of breast cancer in high-risk women by nearly 50%.

A newer group of drugs being developed are called aromatase inhibitors. Unlike tamoxifen, aromatase inhibitors over time do not allow the body to build tumor resistance. Aromatase inhibitors may be a suitable drug for treating patients with hormone dependent breast cancer. Dr. Lippman agrees that the “aromatase inhibitors show great promise as an anti-breast cancer agent.”

Another exciting prospect in the war against breast cancer is the development of vaccines and genetic therapies. About one-third of breast cancer is caused by a gene called erbB-2, which becomes “amplified” or over expressed in some women for reasons that still aren’t entirely clear. When amplified, the gene erbB-2 produces a growth factor signal that fuels the development of breast cancer.

Researchers at the Lombardi Cancer Center are evaluating Herceptin, which is an antibody to the erbB-2 gene. According to Dr. Lippman, “studies show that the antibody targets this gene and blocks the growth factor receptor. This in turn leads to cancer cell death. This approach is made even more successful when combined with traditional chemotherapy.”

The Future
In addition to detecting cancer in breast fluid ahead of mammography, Lombardi researchers are now taking science a step further by identifying specific genetic mutations in single, breast tissue cells.

By screening individual cells, it is possible to identify genes that promote cancer and genes that suppress cancer. It is these “suppressor” genes, that when defective, allow cancer to grow at an accelerated rate. Of particular concern to Dr. Lippman, he describes the malfunction of these suppressor genes as comparable to, “going downhill in a car with no brakes.”

A mutated “p53” gene appears to be a common denominator for not only breast cancer, but other types of cancer as well. To date, researchers at Lombardi have been able to successfully replace the defective p53 gene with a healthy p53 gene in animal trials by using a common cold virus as a delivery system. For a period of two weeks—the life of the cold virus—the cancerous cells are not only treated with healthy p53 cells, but given a double punch with the addition of radiation therapy.

To date, the laboratory success of this combination has shown promise. Human trials with p53 genetic therapy will begin at the Lombardi Cancer Center as early as this year. Dr. Lippman speaks enthusiastically about the future of genetic therapy and other biological approaches, which he believes, “represent extraordinary developments that are ushering in a new era of treatment.” For more information or a physician referral, please call the Lombardi Cancer Center at (202) 784-4000.

Return to top of page