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Micrometastases and Isolated Tumor Cells in the Lymph Nodes: What Do They Mean for Breast Cancer Patients?

Micrometastases and Isolated Tumor Cells in the Lymph Nodes: What Do They Mean for Breast Cancer Patients?

• SAN ANTONIO—Interest has been growing for several years in determining the prognostic significance of micrometastases and isolated tumor cells (ITCs) in the lymph nodes of breast cancer patients. Several presentations at the 29th San Antonio Breast Cancer Symposium (SABCS) shed light on this issue—but did not reach a consensus. Micrometastases are defined as lesions 0.2 to 2.0 mm and are detected by step-sectioning H—E staining, while ITCs (sub/nanomicrometastases) are less than 0.2 mm and are usually found only by immunohistochemical staining (IHC).

In a Plenary Lecture, Emiel Rutgers, MD, PhD, a surgeon associated with the Netherlands Cancer Institute, Amsterdam, noted that few oncologists currently recommend adjuvant therapy for patients based solely on the presence of micrometastases. Nonetheless, many worry about possible disease progression in these patients.

Based on multivariate analyses in a number of studies, the finding of occult micrometastases in the lymph node is not a significant prognostic factor for poorer survival, Dr. Rutgers maintained. He drew on several studies, including most recently a study from SABCS in 2005 by Cox C et al, who reported that the chance of having "further involvement" in the nodes after initial sampling was 14%, equally divided between micrometastases and isolated tumor cells. After a mean follow-up of 2 years, for patients with T1 or T2 tumors, there was no difference in disease-free survival between patients with these minute lesions and patients who were completely node negative, Dr. Rutgers said.

In another study from the John Wayne Cancer Center, 5-year disease-free survival was approximately 98% for patients with either micrometastases or IHC-negative nodes, but only 73% for patients with macrometastases.

But micrometastases can indicate the presence of metastases in additional axillary nodes, he added. In a series of 2,150 patients from his institution, 650 (30%) were found to be sentinel node positive, 18% of whom had macrometastases. Another 7% had micrometastases, and 5% had ITCs, for a 12% rate of submacrometastases, which is in keeping with other series, he noted. Complete axillary dissection of these patients revealed micro- or macrometastases in additional nodes in 19% of patients, resulting in upstaging in 15% and prompting treatment changes in 7%. Isolated tumor cells heralded additional metastases in less than 8%, and prompted no treatment changes.

"In conclusion, the prognostic significance for survival when you have micrometastases only, with all axillary lymph nodes examined, is unclear and, at most, limited," Dr. Rutgers maintained. "Prognosis is related to size of the metastasis and the primary tumor characteristics."

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