Each woman who comes to the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine for breast cancer treatment gets a team of physicians dedicated to her case. The team members understand that each patient is unique: her health, her daily life, her hopes — and her cancer.
That’s why they strive to develop personally tailored treatments that give the most benefit with the mildest adverse effects for each woman who comes through their doors. And as top experts in their fields, they are involved in research that is changing the way breast cancer is treated here and around the world.
Identifying the type
The breast cancer program at Siteman is led by medical oncologist Matthew Ellis, MB, BChir, PhD, a world leader in cancer genetics and the clinical management of breast cancer.
Among Ellis’ recent accomplishments is work to sequence the genomes—the full collection of genetic material— of breast cancer patients, performed in conjunction with Washington University’s Genome Center.
"Buried in the complex genome of breast tumors is information about which treatment patients should get," Ellis says. "Ideally, we would like to understand all the molecular changes occurring in these cancers."
Most physicians who study breast cancer now recognize there are at least four different subtypes of the disease, each with a specific genetic signature: luminal A, luminal B, HER2-enriched and basal-like. Research at academic centers like Washington University continually refines knowledge of what treatments work best for each type.
For example, Ellis is leading a nationwide clinical study of women with estrogen-receptor (ER)-positive breast tumors to optimize therapy after surgery. ER-positive is the most common breast cancer, accounting for three-quarters of cases. The luminal A and luminal B subtypes are generally ER-positive.
Before surgery, women in the study receive an estrogen-lowering drug that cancels out estrogen’s growth-promoting effect on breast tumors. How the tumor reacts can reveal how well the patient will respond to chemotherapy after surgery. It may even show that chemotherapy is unnecessary for some patients.
"In a typical breast cancer patient, the practice has been to remove the tumor before giving drugs. But without the tumor in place, it’s impossible to check on the effect of the medical treatment on the disease.
"In this particular trial, we give estrogen-lowering therapy before surgery and see if the tumor’s growth rate decreases. If it does, the treatment is working. If it doesn’t, we need to do something else. We learn about the tumor’s responsiveness in the best possible way — directly from the individual cancer under treatment."
Although identification of breast tumor subtypes has opened the door to more individualized care, it can be difficult to accurately assign tumors to their subtype. Ellis and colleagues from across the country have developed a test that uses 50 genes found in breast-cancer samples to precisely classify tumors. The test is expected to be available for clinical use soon.
Ellis has also developed a way to score a patient’s tumor to estimate risk of relapse. His preoperative endocrine prognostic index (PEPI) score could bring good news to many women diagnosed with early-stage ER-positive breast cancer: A low PEPI score means they have little risk of relapse and can safely avoid chemotherapy.
Targeted medical therapy
Research on breast cancer genetics could lead to the development of targeted drugs for cancers that cannot be cured with current therapies. But it’s important to note that most breast cancers do respond to existing drugs.
"Today, 83 percent of patients are cured of breast cancer," Ellis says. "The key is to identify that 83 percent so we can treat them with effective available therapies and focus our research efforts on the 17 percent who are resistant to current treatments."
Standard chemotherapy drugs are designed to destroy any rapidly dividing cells, such as those in breast tumors.
"Doxorubicin, cyclophosphamide and paclitaxel or docetaxel are the drugs most often used for chemotherapy," says Julie Margenthaler, MD, a Washington University breast surgeon at Barnes-Jewish Hospital. "There are many different protocols for administering these agents now, and there are also many experimental drugs that have been shown to be effective. Our doctors put a lot of thought into giving the right drugs to the right person."
Targeted treatments are currently available for certain breast cancers. Trastuzumab (Herceptin) is used against HER2-enriched tumors. Tamoxifen and other anti-estrogen therapies are used for ER-positive tumors.
Recently, Ellis demonstrated that estrogen hormone therapy could be an appealing alternative to chemotherapy for women with metastatic breast cancer that has become resistant to estrogen-lowering agents. For some of these women, a daily low dose of estrogen stopped the growth of tumors or even shrank them. In some cases, the estrogen therapy reversed the cancer’s resistance to the estrogen-lowering agents, making the agents effective treatment options once again.
Other advances are available to select patients through clinical studies that test the safety and effectiveness of new therapies before these therapies are widely available. Siteman offers more clinical studies for breast cancer than any other center in the region.
Approximately 25 percent of Siteman’s breast cancer patients participate in clinical studies.
If breast cancer spreads beyond the primary tumor, it goes first to the lymph nodes under the arm. In the past decade, the standard practice of surgically removing the lymph nodes to check for cancer — which can injure nerves or cause arm swelling and shoulder dysfunction — has given way to gentler procedures in which only the lymph nodes directly connected to the tumor need to be removed for testing. Called sentinel node mapping and developed at Washington University, this method saves healthy lymph nodes.
Even less invasive procedures are on the horizon. Siteman physicians, led by Margenthaler, are conducting a study using sophisticated ultrasound and light-based scans to locate the sentinel lymph nodes — those that draw fluid from the tumor. Then they will use a needle to sample these nodes and test for a genetic fingerprint that indicates cancer. If the test is negative, the lymph nodes can stay in place.
This effort continues a drive to lessen the impact of surgery on breast cancer patients, which is reflected in a dramatic increase in lumpectomy rates over the past 30 years.
"In 1970, 90 percent of women in the United States with breast cancer had mastectomies, and now it’s only about 30 percent," Margenthaler says. "Our goal is to get the same good cancer-control outcomes with the least invasive surgical approaches."
Breast reconstruction after cancer surgery can help restore a woman’s confidence. For most Siteman breast cancer patients, a plastic surgeon is brought in at the very beginning of the surgical treatment process. Eighty percent of Siteman patients receive reconstruction when undergoing mastectomy, while nationwide the rate is less than 10 percent.
"It’s not a matter of vanity," says Terence Myckatyn, MD, a Washington University plastic surgeon who performs breast reconstruction. "It’s just getting back to normal. Many women feel they can tolerate waking up after mastectomy if they know that the process of rebuilding their breast has begun."
Artificial implants can replace the breast tissue removed during mastectomy, but other options may be appropriate for some women. An advanced procedure called TRAM flap surgery makes use of tissue from the abdomen to rebuild the breast. The newest versions of this technique have less effect on the abdominal muscles so that recovery is faster.
Though lumpectomy is a less invasive procedure, Myckatyn says women who have this surgery may also be candidates for reconstruction. Options include breast reduction or fat grafting to fill contour defects.
"With all reconstructive procedures, it depends on the location of the tumor and the therapy being used," Myckatyn emphasizes. "Cancer treatment trumps everything else. We get permission from the entire treatment team every step of the way."
The advantage of a dedicated center
The medical oncologists, radiation oncologists, surgeons and plastic surgeons who treat breast cancer at Siteman meet regularly to discuss cases, pooling their skills and knowledge to deliver multidisciplinary care customized for each patient.
"At Siteman, you see surgeons who almost exclusively perform breast cancer surgery," says Imran Zoberi, MD, medical director of radiation oncology at Siteman’s location at Barnes-Jewish West County Hospital. "You see medical oncologists who almost exclusively treat breast cancer, and it’s the same in radiation oncology. And that means every patient gets an extra level of expertise and experience."