NEW YORK CITY-As genetic profiles predicting response to chemotherapy and biological agents gain in importance in pre and post-operative management of breast cancer, sentinel lymph node biopsy and axillary node dissection may be becoming less important.
Speaking here at the Chemotherapy Foundation Symposium, a medical oncologist and a breast cancer surgeon, both from Memorial Sloan-Kettering Cancer Center, came from different perspectives to voice this same opinion.
Medical oncologists can make most systemic treatment decisions without the information provided by a traditional axillary node dissection, said Clifford A. Hudis, MD, Chief of the Breast Cancer Medicine Service at MSKCC and Professor of Medicine at Weill Cornell Medical College.
"My prediction is that lymph node status will be a relatively less important component of oncology decisions in the years to come."
Dr. Hudis explained that the number of involved axillary lymph nodes ipsilateral to an invasive breast cancer has traditionally been a key component of the medical oncologist's decision to recommend adjuvant therapy in general, and chemotherapy specifically. He said the risk of long and short-term toxicities associated with chemotherapy leads most clinicians and patients to reserve chemotherapy for situations where the benefits of treatment exceed the risks by a significant margin.
On the other hand, targeted treatments for breast cancer are generally chosen based on biological facts such as the presence of estrogen or HER2 receptors, Dr. Hudis said. So it could be possible for clinicians to select patients for chemotherapy based on responsiveness to the specific agents employed, as is already standard with hormone and anti-HER2 therapies.
"As this becomes possible, the medical oncologist's need to have an exact assessment of degree of involvement of the axillary nodes by cancer could be diminished," Dr. Hudis said.
Recent developments in the systemic therapy of early breast cancer support this view. For example, he said, the widely used 21-gene recurrence score appears to predict chemotherapy sensitivity independent of the presence or absence of ipsilateral axillary node involvement.
"If confirmed, this could enable medical oncologists to make almost all of their adjuvant treatment decisions without detailed knowledge of the number of involved axillary nodes."
Similarly, the need for an exact node count to determine post-mastectomy radiation therapy, to the extent that radiation is recommended for all patients with any number of involved nodes, is also less.
Z0011
Dr. Hudis acknowledged that this opinion is provocative, given the amount of evidence supporting axillary node dissection. He reviewed familiar data from the Z0011 study, which randomly selected patients with positive sentinel nodes-"once the bellwether for completing a dissection"-and randomized them to complete the axillary dissection or to leave the nodes in place. (He noted that his own institution could not participate in Z0011 for fear that it was borderline unethical- "shows you where we were," he said, sotto voce.)
Overall survival in that trial showed no difference. "But what was hidden in that [data] was that 27.4% of patients who did go for dissection had positive lymph nodes. That means a full quarter of patients who did not go for dissection had positive lymph nodes-ergo, leaving presumably viable cancer in the axilla, and doing nothing about it did not seem to matter."
This, he said, was counter to everything oncologists have learned over many years, that local control mechanically is a first and important step.
"If the biology is driving treatment, the anatomy is less important," he said.
A Surgeon's Perspective
"Sentinel node biopsy works-we all know this; we have many validation studies of SLNB with axillary node dissection backup showing a success rate in the high 90s," said Hiram S. Cody III, MD, Attending Surgeon in the Breast Service of MSKCC and Professor of Clinical Surgery at Weill Cornell Medical College. But "if axillary lymph node dissection for sentinel lymph node-positive patients does not change systemic therapy, or reduce local recurrence, or improve survival, then axillary node dissection for SLN+ patients should be done to salvage local recurrence-a rare event-not to prevent it."
The goals of lymphadenectomy are staging and prognostication, local control, and the possibility of a survival benefit.
"SLN biopsy has become the standard of care for axillary lymph node staging at many institutions worldwide, but what have we achieved?" Dr. Cody asked.
He said numerous trials have demonstrated that SLN biopsy works, with an overall success rate of 96%, and they have confirmed that the sentinel lymph node is the node most likely to be positive while a negative SLN reliably predicts a negative axilla.
But Dr. Cody said several recent developments suggest a diminishing role for axillary lymph node dissection in SLN+ patients, particularly those who receive whole breast radiotherapy. "The future of SLN biopsy is uncertain. We have entered an exciting era in which gene-expression profiling promises more accurate prognostication and prediction of response to therapy than conventional histopathology."
The EORTC 10041 MINDACT trial and the TAILORx trial are testing this premise, he noted. "If these and other trials establish that gene expression profiling is superior to conventional histopathology, particularly in patients with node-positive disease, we must ask whether any form of axillary lymph node staging will remain relevant."
Dr. Cody said the identification of non-axillary SLN is of minimal significance, except perhaps in the reoperative setting. He also said there is no advantage to SLNB prior to neoadjuvant chemotherapy - "There may be a more accurate staging but nothing else is changed."
The Memorial Sloan-Kettering algorithm for such cases calls for no IHC staining in SLN, he said; for patients who meet the Z0011 criteria (cT1-2, N0, WBRT), preoperative axillary ultrasound should be used only for highest risk patients, and ultrasound-fine needle aspiration only for multiple abnormal nodes; no intraoperative frozen sections should be taken; and no ALND should be done for two or fewer positive SLNs.