A Closer Look
Four Breast Cancer Trials with Clinical Implications
At the recent American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Dr. William Wood of Emory University discussed four NCI-supported clinical trials in breast cancer, each with clinically important results. He said that he could not remember a series of four consecutive reports at ASCO “with as clear conclusions that were consequential for practice” as these.
The first trial found that a commonly used test to identify rare cells in the sentinel lymph nodes or bone marrow of patients with breast cancer may not provide useful information for patients and physicians. The test, a method for staining cells called immunohistochemistry (IHC), can detect small numbers of cells, or micrometastases, that would not typically be picked up by a pathologist’s examination of a tissue specimen on a slide.
—Dr. William Wood
The researchers hypothesized that IHC could help identify patients at risk of recurrence and determine which ones might need systemic chemotherapy, but the results suggested otherwise. “We had thought that finding micrometastases using immunohistochemistry would portend a worse prognosis, but we did not find that,” said co-investigator Dr. A. Marilyn Leitch, of the University of Texas Southwestern Medical Center at Dallas.
This prospective multicenter trial included more than 5,000 women with early-stage, clinically node-negative (without palpable metastases in the lymph nodes under the arm) breast cancer who had undergone lumpectomy. The women also underwent sentinel lymph node biopsies and bone marrow aspiration to determine whether micrometastases were present.
“In general, as a result of this study, these special stains should probably no longer be done in women with newly diagnosed breast cancer,” said Dr. Eric Winer of Harvard Medical School, who moderated a press briefing. The findings should have an impact on care because IHC is routinely done at many medical centers, he noted.
Regarding the bone marrow test, there was a suggestion of worse outcome in women who were found to have tumor cells in the bone marrow as detected by IHC. But this approach requires further investigation, said Dr. Winer. “I don’t think any of us would recommend that a woman with newly diagnosed breast cancer undergo a bone marrow examination as part of her routine evaluation,” he added.
Improving Quality of Life
Another study in the session was NSABP B-32, a large randomized phase III trial that compared sentinel lymph node biopsy with axillary dissection in clinically node-negative women with breast cancer. The study concluded that, in these women, axillary lymph node dissection did not add a benefit to sentinel node biopsy alone.
“When the sentinel node is negative, sentinel node surgery alone with no further axillary dissection is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes,” said Dr. David N. Krag of the Vermont Cancer Center, who presented the findings. “This is clear evidence of a study that adds benefit to a woman’s quality of life and is also cost-saving.”
Dr. Wood praised the trial’s design and focus on surgical quality control, and he agreed with its conclusion, calling the evidence “definitive.”
In a related trial, researchers found that removing additional axillary lymph nodes to look for more breast cancer cells in women with limited disease that had spread to the sentinel node did not improve survival. These findings are important because many physicians routinely opt for axillary node dissection in women with metastases in the sentinel lymph node, the researchers said.
Axillary lymph node removal has been the standard approach for women with micro- and macrometastases in the sentinel node, explained lead author Dr. Armando Giuliano, director of the John Wayne Cancer Institute Breast Center in Santa Monica, CA. The results are not definitive, noted Dr. Winer, because the study did not meet its goal in accrual.
But the findings suggest that there may not be a benefit to removing more lymph nodes than the sentinel node in such cases, and that many women can avoid the risk of additional side effects associated with more extensive lymph node removal, Dr. Giuliano said. Axillary lymph node dissection will still be needed in some cases, but these findings show it may be necessary for far fewer women, he added.
Helping Older Patients
A fourth trial found that some older women can forgo radiation after surgery for breast cancer. Women 70 years of age or older with early-stage breast cancer did not benefit from the addition of radiation therapy to breast-conserving surgery and tamoxifen, according to the results from a phase III randomized trial. (See the full NCI Cancer Bulletin article.)
“These clinical trials, which were made possible only through government funding, will spare many women the side effects of unneeded treatment without compromising their survival,” said Dr. Jo Anne Zujewski, head of Breast Cancer Therapeutics in NCI’s Division of Cancer Treatment and Diagnosis. “They will also help save health care dollars.”
Dr. Wood concluded his discussion of the four reports by saying: “These are practice-changing results. And it’s also interesting to see scientific hypotheses proven, even if it’s only the null hypothesis.”
—Edward R. Winstead