ASCO 2009: Sentinel Node Micrometastases Need Additional Treatment in Breast Cancer

Don't ignore micrometastases.

That is the main message from a Dutch study of women with early-stage breast cancer presented here at the American Society of Clinical Oncology (ASCO) 45th Annual Meeting.

One of the groups of women studied had micrometastases (nodal disease that measures 0.2 to 2.0 mm) discovered by sentinel lymph node biopsy (SLNB).

These women had a significantly higher rate of recurrence in the axillary nodes if they did not receive follow-up treatment, according to study results.

Follow-up treatment was either completion axillary lymph node dissection (cALND) or, less commonly, axillary radiation.

After 5 years, there was a 5% rate of axillary recurrence for the women with micrometastases who only had a SLNB (n = 141) and no follow-up treatment, compared with a 1% rate for those who had either cALND or radiation (n = 887; hazard ratio, 4.39).

This 5-year recurrence rate is much too high.

"This 5-year recurrence rate is much too high. And it will likely increase with longer follow-up," said lead author Vivianne Tjan-Heijnen, MD, PhD, at a meeting press conference. She is professor of medical oncology at the Maastricht University Medical Center in the Netherlands.

The new Dutch study, dubbed MIRROR (Micrometastases and Isolated Tumor Cells: Relevant and Robust or Rubbish?), conflicts with a recent large American study. The latter found that follow-up treatment with cALND did not improve either axillary recurrence or survival for patients with microscopic disease, as reported by Medscape Oncology. The senior author of the American study said: "We have relied upon [cALND] too much."

However, Dr. Tjan-Heijnen told Medscape Oncology that there are a number of important differences between her study and the American study, all of which strengthen the authority of her group's findings.

She also noted that ASCO guidelines support her findings. "Completion axillary lymph node dissection is recommended in patients with micrometastases," she said, acknowledging that the procedure is associated with an increased rate of lymphedema.

An American breast cancer expert attending the meeting felt swayed by the Dutch findings. "We might have to be more aggressive with micrometastases — they should not be ignored," Julie Gralow, MD, told Medscape Oncology. Dr. Gralow is a member of the Fred Hutchinson Cancer Research Cancer in Seattle, Washington, and serves on the ASCO Communications Committee.

"We have struggled with what to do with micrometastases," observed Dr. Gralow. "Should we avoid further surgery and use radiation? It's important to know that axillary radiation is separate from breast radiation and also produces lymphedema," she added, noting that the standard of care in this situation has been cALND, but clinical judgment comes into play.

In the end, Dr. Gralow was impressed by the new findings: "I am going to use these data with my patients."

Another American clinician at the meeting felt similarly. "We have never known exactly how to approach these cases. The MIRROR study helps us have a further educated discussion with our patients," said Jennifer Obel, MD, a medical oncologist from the NorthShore University HealthSystem in Evanston, Illinois, and also a member of the ASCO Communications Committee

Dr. Gralow pointed out that, in early breast cancer, the majority of women can avoid any follow-up treatment because the SLNB is negative.

Isolated Tumor Cells and Micrometastatic Disease: The Differences

One of the key differences between the recent American and Dutch studies is that they worked with different definitions of the small amounts of disease that can be found by SLNB.

The difference here is not just an academic matter, it is a key to understanding how to proceed clinically, suggested Dr. Tjan-Heijnen.

In the Dutch study, the investigation separated microscopic disease into 2 groups: the smaller isolated tumor cells (<0.2 mm)>

The American study did not separate the 2 classifications because, before 2002, both categories were "lumped together," and thus were analyzed as "microscopic" disease, said Dr. Tjan-Heijnen, explaining that the American study's outcome findings date from before 2002.

The Dutch findings show that isolated tumor cells and micrometastases produce different outcomes and should not be treated the same way by clinicians.

Specifically, in the Dutch study, after 5 years, patients who were found to have isolated tumor cells by SLNB and who did not subsequently undergo cALND (n = 732) did not have a significantly higher rate of axillary recurrence than similar patients (n = 125) who did undergo cALND (2.3% vs 1.6%).

In other words, it's okay to not do a follow-up treatment in patients with isolated tumor cells, said Dr. Tjan-Heijnen.

However, Dr. Tjan-Heijnen qualified this recommendation a bit further: "These patients should have favorable tumor characteristics," she said, explaining that any patient with a grade 3 tumor should have follow-up treatment for any kind of nodal disease.

The Dutch study found that patients with micrometastases all need follow-up treatment, as noted above.

The quality of data in the Dutch study was superior in other ways, said Dr. Tjan-Heijnen. Data used in the American study were obtained from a cancer registry and did not undergo a central pathology review, whereas the Dutch data did undergo a central pathology review. According to Dr. Tjan-Heijnen, the authors of the American study admitted that their data on axillary recurrence were incomplete; the Dutch study had axillary recurrence data for all patients.

More About MIRROR

The Dutch MIRROR study is the largest cohort study on micrometastases and isolated tumor cells in the sentinel node era, say the study authors.

"The sentinel node is intensively examined to prevent false negatives," said Dr. Tjan-Heijnen. She also said that this intensity has led to increased detection of micrometastases and isolated tumor cells.