Less is Best: Node Removal Not Necessary in Some Patients

Initiated in the 1970s, the National Surgical Adjuvant Breast and Bowel Project B-04 study demonstrated survival was the same in patients given a total mastectomy compared with just removal of the tumor and surrounding tissue followed by radiation to the remainder of the breast. Then, in the 1990s, research showed women with a clean biopsy of the “sentinel” node (the first lymph node that metastasizing cancer cells would go to) might be spared an axillary lymph node dissection (ALND), in which dozens of additional connecting nodes are potentially removed from the armpit.

Now researchers have found that a select group of early-stage breast cancer patients may not need ALND even if one or two sentinel nodes contain tumor cells. Skipping ALND eliminates common side effects of the procedure, including painful and chronic swelling of the arm, known as lymphedema, and infection. Yet again, less is best.

In two reports on study Z0011 published in the Annals of Surgery and the Journal of the American Medical Association, researchers from the American College of Surgeons Oncology Group showed that ALND is not beneficial, with the most recent one yielding 92 percent survival whether they had only one or two sentinel nodes removed for examination or an additional 17 axillary nodes, on average.

The patients studied had one or two positive sentinel node biopsies and were treated with lumpectomy and whole-breast irradiation. Additionally, up to 97 percent of patients received postoperative systemic hormonal or chemotherapy, with about half receiving chemotherapy.

These disease characteristics and treatment plans describe about 20 percent of breast cancer patients now being cared for—up to 40,000 women a year in the U.S.

Researchers successfully tested the hypothesis that radiation and chemotherapy eliminated the cancer in the lymph nodes of these patients, says the study’s senior investigator, Armando Giuliano, MD, executive vice chairman of surgery for surgical oncology at Cedars-Sinai Medical Center in Los Angeles. Giuliano introduced sentinel node biopsy for the treatment of breast cancer in the early 1990s.

He says the findings suggest that “there is something about the biology of lymph nodes that we underappreciate—that maybe these cancers tend not to metastasize from lymph nodes.”

Among other oncologists, Eric Winer, MD, director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston, welcomes the findings, saying they will strongly influence clinical practice.

“We have to be careful not to extrapolate beyond the study,” he adds, “but for women who met the criteria, I think it really says a fair amount.”

Some researchers have questioned the fact that enrollment was half of what was originally planned and that follow-up time was limited to six years.

These are non-issues, Giuliano counters. “Our survival was so high, and local recurrence so low, that the targeted accrual of patients was an underestimate,” he says. “And most surgery and radiation achieve their impact by local control, and locoregional failures are early. In this study, most axillary recurrences are in the first two years.”

“We have known for a long time that radiation and chemotherapy can control regional nodal metastasis,” says Grant Carlson, MD, of the Winship Cancer Institute of Emory University in Atlanta. But, he adds, “the development of sentinel lymph node mapping and increased patient awareness regarding the morbidity of axillary dissection have been drivers to question what has been regarded as the standard of care.”

If the findings of the two studies result in changes in patient management, Giuliano hopes subsequent trials will show that less surgery could be extended to other patients: those with larger tumors or with more lymph node involvement. “Other researchers are thinking about such a study,” he says, “and if it happens, I predict it will be very successful.”