Treating Patients, Seeking Answers -
New Breast Center's Mission Will Be Two-Fold

A new breast center at Baylor College of Medicine and The Methodist Hospital is attacking breast disease on two fronts: in the clinic and at the microscope.

A "One-Stop" Location for Breast Care Needs

"We're going to offer, in one location, everything you need if you have a breast problem," says Dr. C. Kent Osborne, of the Breast Center's 21,000-square-foot clinical facility scheduled to open across the street from The Methodist Hospital in Smith Tower next month. Dr. Osborne, a recent addition to the Baylor College of Medicine faculty from The University of Texas at San Antonio, will serve as the director of the Breast Center, which currently includes 16 other faculty members.

For example, a woman could receive a screening or diagnostic mammogram at the center, and if a lump is detected, also undergo a biopsy and, eventually, chemotherapy in the same location. Genetic testing and counseling, psychological, nutritional and social support services and prevention information will also be available. Patients and their physicians will also have access to research studies. In addition, the facility will include a lymphedema clinic.

"Since everything is under one roof, a woman might be able to get some of her appointments all in the same day. That's the goal. It's difficult to do that in every case, but at least it will be in the same location so that a patient won't have to be going all over town for her information," says Dr. Osborne, professor of medicine and cell biology at Baylor. Specialists ranging from radiologists to surgeons will all be seeing patients in the Center. Staff physicians include both full time and volunteer Baylor and Methodist faculty.

"When I first started seeing breast cancer patients and doing breast cancer research back in the mid-70s and into the 80s, maybe 5 or 10 percent of women who were supposed to be getting mammograms were getting them," he says. "Now, it's a much, much higher percentage. We still have a long way to go in certain segments of the population, but overall we're doing much better."

Dr. Osborne attributes the decline in the breast cancer mortality rate in the 1990s to the improvement of treatments like chemotherapy and tamoxifen and, potentially, to the increased use of mammography to detect breast cancer. "It's a little too early yet to see the mortality improvement due to mammography use because it wasn't until the mid- to late-80s that a greater percentage of women started to get mammograms," he says. "Those statistics are going to show up in the next five years and the mortality reductions will be even greater."

Predicting the Behavior of the Tumor

The second component of the Breast Center will find scientists in the lab on the 11th and 12th floors of Baylor's Albert B. Alkek Graduate School of Biomedical Sciences building, researching ways to diagnose, treat and even prevent breast cancer in the future.

Dr. Peter O'Connell is one of those scientists. He and other colleagues, formerly of UT-San Antonio, recently made a discovery about genetic changes that may have an effect on the spread of breast cancer, or its metastasis, to other parts of the body. Their research findings were published in the August 18 issue of the Journal of the National Cancer Institute.

"We're interested in genetic profiling of breast cancers and the idea is that we want to measure genetic changes and then correlate them with tumor behavior," says Dr. O'Connell, also a professor at Baylor.

The results with regard to metastasis were contrary to their initial expectations. The researchers used a series of genetic markers to measure the levels of LOH or loss of heterozygosity. LOH events commonly occur in two ways during tumor development - tumors amplify genes that can help the tumor grow, or tumors can inactivate genes that control cell growth. In this study, the researchers looked at LOH levels in precursor lesions for breast tumors, breast tumors themselves and metastatic lesions.

Their hypothesis that the level of LOH events would increase with tumor development was vindicated until they reached chromosome 14. "We saw the increasing rates as we went from the pre-malignant to the fully malignant lesions, but the rate dropped in the metastatic lesions. That was a surprising result for us," says Dr. O'Connell.

The researchers then sorted the primary breast cancers into two groups: those with no evidence of local spread (node-negative) and those where the tumor had spread locally (node-positive) and found that the rate of LOH was higher in the node-negative primary breast cancers than in the node-positive at this particular marker.

"If we can predict the behavior of the tumor by its genetic profile using a marker like this, we can help pathologists and oncologists come up with a better treatment plan," says Dr. O'Connell.

"The other obvious thing we want to do with this information is to identify what this gene is because it seems that reducing levels of this gene impedes metastasis. So that might be a gene therapy or drug therapy target to give to women at diagnosis to help control the spread of the disease," he says.

Dr. O'Connell and his colleagues are now conducting further research to test these findings and to isolate and identify the gene.

Viewing Breast Disease at the Molecular Level

Other research efforts at the breast center include:

• Trying to identify how breast cancer becomes resistant to the drug tamoxifen. "Tamoxifen is a great drug and it works for awhile in lots of patients, but in many of those patients, the tumor becomes resistant and begins to grow again," says Dr. Osborne. "We're trying to figure out how and why that occurs and how we can prevent it, prolong it or reverse it. I think we have some interesting clues." Researchers are also studying a new drug that may benefit those patients who have breast cancer that is resistant to tamoxifen.
• Participating in the STAR trial (Study of Tamoxifen and Raloxifene). This study, taking place at more than 400 sites in the United States, Canada and Puerto Rico, will follow approximately 22,000 women to determine which drug is the most effective and the safest for women at high risk of developing breast cancer.
• Studying benign breast disease to understand when and how it develops into breast cancer. "We know that women with pre-malignant breast disease have a slightly increased risk of getting cancer someday, but it is hard to study because the abnormalities are so small," says Dr. Osborne. "Now, there are molecular techniques that have permitted us to begin study."
• Working to develop a profile of a patient's individual tumor in hopes of targeting treatment options. "We are looking at factors associated with the cancer or the patient that help to decide how aggressive the cancer is going to be in that patient and whether it will respond to treatment," says Dr. Osborne.
• Identifying ways in which gene therapy can be used to treat breast cancer effectively and safely. "I'm intrigued by the possibility of preventing breast cancer by correcting a BRCA1 gene, for example," Dr. Osborne says.

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©2006 Texas Medical Center

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