BETHESDA, MarylandA key issue for oncologists treating breast cancer patients with preoperative chemotherapy remains whether to perform sentinel lymph node (SLN) biopsy before or after administering the drugs. Two questions dominate the debate: Does sentinel node biopsy work as well following preoperative therapy as it does in patients who do not receive neoadjuvant treatments? Is information important to managing patients lost when physicians delay SLN biopsy until after the drug treatments?
Two oncologists versed in this neoadjuvant therapy debate presented the pros and cons at "Preoperative Therapy in Invasive Breast Cancer," a 2-day state-of-the-science conference sponsored by the National Cancer Institute. Terry Mamounas, MD, MPH, associate professor of surgery, Northeastern Ohio University College of Medicine and medical director of the Aultman Cancer Center, Canton, Ohio, provided the case for SLN biopsy after neoadjuvant therapy. Jay Harris, MD, chief of radiation oncology, Dana-Farber Cancer Institute, and professor of radiation oncology, Harvard Medical School, presented the merits of SLN biopsy prior to preoperative treatment.
The Issue of Downstaging
The issue of SLN biopsy timing stems from the downstaging of positive axillary nodes that can occur with neoadjuvant therapy. In four studies cited by Dr. Mamounas, for example, researchers observed downstaging in 19% to 43% of patients. Dr. Harris cited results from National Surgical Adjuvant Breast and Bowel Project (NSABP) study B-18 in which the proportion of patients with positive nodes dropped from 57% to 41%, and that of patients with four or more positive nodes dropped from 27% to 16%, with neoadjuvant chemotherapy, compared with adjuvant therapy.
As long as axillary dissection remained the sole staging method, the finding had no clinical significance. "However, the advent of sentinel node biopsy produced another potential benefit from neoadjuvant chemotherapy, and that is the potential for decreasing the extent of axillary surgery with sentinel node biopsy if the axillary nodes are downstaged," Dr. Mamounas said. "The big question is, of course: Is sentinel node biopsy as feasible and accurate after neoadjuvant therapy as it is before any systemic therapy?" Dr. Mamounas argued that it is.
Data from early single-institution studies showed considerable variation in the rates of sentinel node identification after neoadjuvant chemotherapy, from 72% to 100%, and in false-negative sentinel nodes, from 0% to 33%, Dr. Mamounas noted. Later single-institution studies set more precise numbers. "If you look at all of them together, you see the overall identification rate is about 89%, with a false-negative rate of 10.8%," he said.
NSABP study B-27, a large, multicenter trial, provided researchers a look at the performance of SLN biopsy following preoperative chemotherapy. In 428 women, a sentinel node biopsy was followed by an axillary node dissection. The identification and false-negative rates varied, depending on whether surgeons relied on blue dye staining alone or also used radiocolloid. "The identification rate was 85%, higher if isotope was used," Dr. Mamounas said. "The false-negative rate was about 11%, and, again, it was higher if only blue dye was used and lower if isotope was used."
Moreover, a meta-analysis of 21 single-institution and multicenter studies with a total of 1,273 patients estimated the identification rate at 90% and put the false-negative rate at 12%. "So the conclusion from the meta-analysis was that sentinel node biopsy is a reliable tool for planning treatment after neoadjuvant therapy," Dr. Mamounas noted.