SAN ANTONIO, TX-Axillary dissection should no longer be the automatic default if a positive sentinel node is found in a clinically node-negative woman with breast cancer having breast-conservation surgery. That was the word from Monica A. Morrow, MD, speaking here at the Society of Surgical Oncology Annual Symposium.
"I think we have reached the era where biologic features are the primary determinant of prognosis and systemic treatment for the overwhelming majority of patients," said Dr. Morrow, Chief of the Breast Service and Chair of Clinical Oncology at Memorial Sloan-Kettering Cancer Center and Professor of Surgery at Weill Medical College of Cornell University.
In a symposium titled "Management of the Clinically Negative Axilla-Time for a Change?," sponsored by Susan G. Komen for the Cure, Dr. Morrow said that a sentinel node can be identified in almost all breast cancer patients and cited two randomized studies that validated the sentinel lymph node concept, ACOSOG Z0010 and NSABP-B-32, which combined include more than 10,000 women and 500 surgeons.
She noted that the studies used different techniques of lymphatic mapping using either radioisotope and blue dye-as mandated by B-32, surgeon's choice in ACOSOG Z0010-or blue dye alone, and the training methods were also somewhat different. Still, the studies were similar in finding a sentinel lymph node in approximately 98% of women with early stage breast cancer, with a positive sentinel node found in approximately 25%, she said.
Two other randomized trials found that sentinel lymph node biopsy reliably staged the axilla, with no difference found in the likelihood of nodal metastases between sentinel node biopsy alone and axillary dissection-JNCI 2006;98:599-609, the ALMANAC Trial; and Veronesi et al: NEJM 2003;349:546-553.
"In a direct randomization, the likelihood of identifying nodal disease does not differ between these two techniques, because just like there's a false-negative rate for sentinel node biopsy, there's a false-negative rate for axillary dissection," she said.
"It just happens to be the pathologist's false-negative rate," she said, eliciting a bit of laughter from the audience, adding, in an aside, "but they don't like to admit that."
Dr. Morrow said that at this time it is possible to conclude that sentinel node biopsy in its maturity allows oncologists to identify a sentinel node in almost all women with early-stage breast cancer; that it reliably identifies nodal metastases with substantially lower morbidity than axillary dissection; that when the sentinel node is negative to tumor, the likelihood of axillary first failure is less than 1%; and there is no survival impact between the two procedures.
"Or to put this in a slightly more direct way, if you don't know how to do this operation, you shouldn't be operating on breast cancer," she said.
Micromets of Little Prognostic Importance
Micrometastases were a bit more frequent in the B-32 study-16% of cases compared with 10.5% of cases in ACOSOG Z0010, and in B-32 the presence of micrometastases was associated with a slightly worse outcome than the absence for disease-free survival, distant disease-free survival, and overall survival.
But the magnitude of this difference is relatively small, under 3% in all of these areas, she said, and in ACOSOG Z0010 there was no difference in survival at five years.
"Micrometastases in isolated tumor cells are rarely the sole indication for systemic therapy," Dr. Morrow said. "Their prognostic impact is considerably smaller than that seen with macrometastases, and therefore the absolute benefit of added treatment is correspondingly less."
She said that micrometastases are seen in association with other tumor features such as larger size and younger age that are already associated with poorer prognosis.
And although micrometastases are more common in estrogen-receptor (ER) positive tumors, it is the molecular characteristics of ER-positive breast cancers that predict the benefits of chemotherapy, not the presence or absence of nodal metastases, she said.
Dr. Morrow concluded that in individualized axillary management for women for T3 or N1 disease, or any T or N with mastectomy, or any woman receiving neoadjuvant therapy, preoperative documentation of nodal disease with ultrasound and fine needle aspiration avoids sentinel lymph node biopsy and obtaining frozen sections minimizes reoperation.
For women with T1-T2-N0 breast cancer; identification of single abnormal axillary nodes with ultrasound and fine needle aspiration does not change management; frozen section of the sentinel node is no longer routine; and patients with three or more involved sentinel nodes on final pathology should be returned to the operating room for axillary dissection.
She added that the cost effectiveness of ultrasound to identify extensive axillary disease in cN0 patients requires more study.