Major Breast Cancer Study: Stop Routine Use of Axillary Dissection

Nick Mulcahy

June 10, 2010

Dr. Armando Giuliano

June 10, 2010 (Chicago, Illinois) — Routine use of completion axillary lymph node dissection (ALND) is not needed in women with breast cancer who have only 1 or 2 positive sentinel lymph nodes because it does not improve survival, according to a study presented here at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting.

The conclusion of this study might not be palatable to all clinicians, admitted the lead investigator.

The fact that axillary dissection is not needed in women who have positive sentinel nodes is "counterintuitive and hard to accept," because it means not removing all the cancer, said Armando E. Giuliano, MD, director of the John Wayne Cancer Institute Breast Center in Santa Monica, California.

However, when Dr. Giuliano presented his findings, he received warm applause and no combative questions from the audience.

It's hard to abandon it.

"Since we have always done axillary dissection, it's hard to abandon it," Dr. Giuliano noted at a meeting press conference.

No Difference in 8-Year Survival

Dr. Giuliano led the trial of 856 women with clinical T1-2 N0 M0 disease and 1 or 2 positive sentinel lymph nodes.

In the study, which was sponsored by the American College of Surgeons Oncology Group (ACOSOG), the women all received a sentinel lymph node dissection (SLND) and were found to have at least 1 positive node. They were then were randomized to either no further treatment (n = 436) or ALND (n = 420).

The investigators found that, at 8 years, there was no significant difference in overall survival between patients treated with SLND alone (92.5%) and those treated with completion ALND (91.8%; = .25).

There was also no significant difference in disease-free survival between patients treated with SLND (83.9%) and those treated with ALND (82.2%;= .14).

Only older age, estrogen-receptor-negative disease, and lack of adjuvant systemic therapy — not type of surgery — were statistically significantly associated with worse overall survival on multivariable analysis, said Dr. Giuliano.

However, William Wood, MD, from Emory University School of Medicine in Atlanta, Georgia, who acted as the discussant of the study, suggested that the trial does not apply to all women with early breast cancer and positive sentinel nodes. "I call your attention to the caveats in this trial," he said. Dr. Wood noted that the study excluded any patient who had 3 or more positive sentinel nodes, matted nodes, metastases in a sentinel node detected by immunohistochemistry, or third field nodal irradiation.

Another breast cancer expert at the meeting said that the study conclusion conflicts with standard practice.

The role of this operation needs to be reconsidered.

"The majority of doctors are still doing axillary node dissection when sentinel lymph node biopsy is positive on [hematoxylin and eosin staining]," said Thomas Julian, MD, from Allegheny General Hospital in Pittsburgh, Pennsylvania, who is an investigator with the National Surgical Adjuvant Breast and Bowel Project.

Dr. Julian, who was approached by Medscape Oncology for comment, said he respected the ACOSOG study but said that he did not think it was the "final, final word" on the subject.

Dr. Giuliano acknowledged that the ASCO guidelines call for ALND when a positive sentinel node is found and that it is the "gold standard."

Importantly, Dr. Giuliano did not claim that ALND should be avoided in all women with positive sentinel nodes — just a lot more of them.

"The role of this operation needs to be reconsidered," concluded Dr. Giuliano.

"We have to selectively avoid doing completion axillary lymph node dissections," he said, noting that ALND is associated with "a lot more morbidity" than SLND, including pain, discomfort, and lymphedema of the affected arm.

Why the Change Now?

Dr. Giuliano said that, in addition to his study, a number of smaller studies of varying designs from the past 5 years or so did not find ALND to provide a survival advantage.

He had a number of hypotheses to explain why ALND would not offer a survival advantage over SLND alone at this point in the history of breast cancer treatment. And he offered his ideas to the ASCO audience.

In "contemporary breast cancer" practice, he said, the tumors are smaller than in past; there are fewer node-positive patients; the sentinel node is often the only node involved (40% to 70%); breast-conserving therapy is common and tangential-field irradiation treats much of axilla; and finally, adjuvant systemic therapy is usually given for node-positive women. Indeed, in this trial, which took place at 177 institutions, almost all of the women had received chemotherapy, hormonal therapy, or both (96% for the ALND group and 97% for the SLND group).

Dr. Julian agreed that the high percentage of women currently receiving adjuvant therapy for breast cancer has probably affected whatever dangers are posed by positive nodes.

Results in Conflict With Study Presented Last Year

In the ACOSOG study, there was less locoregional recurrence with SLND (2.8%) than with ALND (4.1%), said Dr. Giuliano.

"It is highly improbable that the 2.8% locoregional recurrence would significantly impact overall survival" in the study population, he said.

However, these recurrence results conflict with a Dutch study, known as MIRROR (Micrometastases and Isolated Tumor Cells: Relevant and Robust or Rubbish?), which was presented at ASCO last year and reported on by Medscape Oncology at that time.

In MIRROR, at 5 years, there was a 5% rate of axillary recurrence for the women with micrometastases who only had a sentinel lymph node biopsy (n = 141) and no follow-up treatment, compared with a 1% rate for those who had either ALND or radiation (n = 887; hazard ratio, 4.39).

But Dr. Giuliano pointed out that MIRROR saw no difference in overall survival. It was also a retrospective study, whereas the ACOSOG study is prospective and therefore more authoritative.

It was hard to get women into the trial.

An important fact about the ACOSOG trial is that it closed early and failed to accrue the target of 1900 women.

"It was hard to get women into the trial," said Dr. Giuliano, explaining that they were hesitant out of a fear that they could be randomized to SNLD alone and, thus, less extensive treatment.

Study discussant Dr. Wood doubted that the early closure mattered, and Dr. Giuliano concurred.

Dr. Wood, Dr. Julian, and Dr. Giuliano have disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract CRA506. Presented June 7, 2010.

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