From OncoLog, October 2013, Vol. 58, No. 10
Sentinel Lymph Node Dissection After Neoadjuvant Chemotherapy for Node-Positive Breast Cancer May Replace Axillary Dissection for Some Patients
By Bryan TuttSentinel lymph node dissection has become a standard staging tool for breast cancer patients with no clinical evidence of disease in the lymph nodes.
Recent studies indicate that dissection of the sentinel nodes only, which is less likely than a complete axillary dissection to cause lymphedema and other adverse effects, may also be an appropriate substitute for complete dissection in some patients who present with node-positive disease.
The use of sentinel node dissection alone in patients without clinical evidence of nodal involvement at presentation was validated in 2011 by the results of the American College of Surgeons (ACOSOG) Z0011 trial. In this multi-institutional study, more than 800 women with breast cancer and no palpable adenopathy underwent lumpectomy and sentinel node dissection. Patients with metastatic disease limited to one or two sentinel nodes were randomly assigned to receive axillary lymph node dissection or no further axillary-specific treatment (i.e., no additional surgery or axillary radiation therapy). All patients were scheduled to undergo whole-breast radiation therapy, and the majority received adjuvant chemotherapy. The study revealed no survival benefit from axillary dissection.
These results have changed the approach to axillary dissection for many surgeons. “In patients with clinically negative nodes scheduled for lumpectomy, we used to do frozen-section analysis intraoperatively when we did sentinel node dissection, and if any of the nodes turned out to be positive, we went ahead and did a full axillary dissection. But now that the results of ACOSOG Z0011 are in, we’re not doing the full dissection,” said Kelly Hunt, M.D., a professor in the Department of Surgical Oncology at The University of Texas MD Anderson Cancer Center. “Because if we’re not going to use that information for treatment decisions and the patients aren’t getting a survival benefit from the dissection, why do we need to do that additional surgery?”
Dr. Hunt, who was MD Anderson’s lead investigator for the ACOSOG Z0011 trial and a co-author of the study’s report, said the results of the study led researchers to ask whether some patients with clinically node-positive disease might also be spared axillary dissection and its morbidity.
Axillary dissection remains the standard of care for breast cancer patients who present with clinical evidence of node-positive disease. However, neoadjuvant (preoperative) chemotherapy might make axillary dissection unnecessary in some of these patients. “In recent years, chemotherapy and targeted drugs have gotten so much better that they’re eradicating a lot of nodal disease and therefore making us rethink how aggressive the surgery needs to be afterward,” Dr. Hunt said.
To investigate which characteristics might be used to select patients who could avoid axillary dissection after chemotherapy, Dr. Hunt and her colleagues recently conducted a retrospective study of breast cancer patients who had clinical evidence of lymph node involvement. All patients had undergone initial chemotherapy followed by lumpectomy or mastectomy and lymph node dissection. Most patients had undergone both sentinel node and complete axillary dissection.
The researchers found that patients whose diseased lymph nodes appeared to have normalized on ultrasonography after chemotherapy had a higher rate of pathological complete response in the lymph nodes (51%) than did those whose lymph nodes did not appear on ultrasonography to have responded to chemotherapy (33%). Patients whose lymph nodes had normalized on ultrasonography also had a lower rate (16%) of false-negative sentinel node findings (defined as negative sentinel nodes but disease in at least one non-sentinel node) than did the entire group undergoing sentinel node dissection (21%).
The false-negative rate for sentinel node dissection was higher than expected, Dr. Hunt said. However, multivariate analysis revealed that the technical aspects of the sentinel node surgery have a profound effect on the false-negative rate. Dr. Hunt said that because most patients have two or three sentinel nodes that drain from the tumor to the lymphatics through different channels, removing two or more sentinel nodes was associated with a lower false-negative rate. Also associated with a lower false-negative rate was using both a radiolabeling material—such as technetium 99m—and a blue dye. “When we use that combination of techniques, the identification rate of all the sentinel nodes is improved and the false-negative rate is lower,” she said.
Role of imaging
The retrospective study was possible because it has been standard practice at MD Anderson for many years to examine the axilla, the infraclavicular region, and the internal mammary region along with the breast tumor itself on ultrasonography; thus, images and radiology reports for all patients in the study were available for review. Huong Le-Petross, M.D., an associate professor in the Department of Diagnostic Radiology and one of the co-authors of the study’s report, said she hopes ultrasonography of the axillary nodes along with breast tumors will be widely adopted elsewhere. “Ultrasonography of the axilla helps us provide more accurate staging and helps predict the patient’s prognosis,” she said.
Although Dr. Le-Petross cautioned that imaging studies cannot replace lymph node biopsy, she said ultrasonography can help surgeons detect enlarged nodes that should be removed and can help radiation oncologists plan their treatment fields. For patients undergoing chemotherapy, she said, “Having a baseline ultrasound exam and following up with ultrasonography during therapy can indicate whether that treatment is effective. Evidence of progression or no response in nodal disease might lead an oncologist to alter treatment sooner rather than later.”
Dr. Hunt said her finding that false-negative rates were lower when two or more sentinel nodes were examined was similar to the findings of a prospective study by ACOSOG. The ACOSOG Z1071 trial also evaluated sentinel node dissection in women with clinically node-positive breast cancer who had undergone neoadjuvant chemotherapy. Dr. Hunt said the results of the ACOSOG Z1071 trial—which enrolled more than 700 women at numerous sites, including MD Anderson—will be published soon in the Journal of the American Medical Association.
In an ongoing study, radiologists are placing a clip in enlarged nodes detected during baseline breast ultrasonography. Dr. Le-Petross, one of the radiologists participating in the study, said, “If I see a suspicious lymph node on ultrasonography, I’ll do a needle biopsy and insert the clip at the same time.” Dr. Hunt said she expects the technique to lower the false-negative rate for sentinel node dissection by reducing the likelihood that a diseased sentinel node is overlooked.
In a phase III trial that will soon begin enrolling patients at MD Anderson and other centers, breast cancer patients with clinically positive nodes who have received neoadjuvant chemotherapy will undergo sentinel node dissection; those with at least one positive sentinel node on intraoperative pathological analysis will be randomly assigned to undergo immediate axillary dissection or postoperative radiation therapy to the lymph nodes. “Using radiation instead of removing all the lymph nodes may be another way to reduce morbidity,” Dr. Hunt said.
Although there is great interest in avoiding axillary dissection to reduce morbidity in patients with node-positive disease, Dr. Hunt recommended caution until the results of these studies are known. She said, “We need to be more critical about which clinically node-positive patients we use only sentinel node biopsy in. The initially involved nodes need to appear normal on ultrasonography after chemotherapy. We also need to be sure the technical aspects of sentinel node dissection—using both a radiolabeled tracer and blue dye and removing at least two sentinel nodes—are paid attention to.”
Alvarado R, Yi M, Le-Petross H, et al. The role for sentinel lymph node dissection after neoadjuvant chemotherapy in patients who present with node-positive breast cancer. Ann Surg Oncol. 2012;19:3177–3184.
Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569–575.
For more information, contact Dr. Kelly Hunt at 713-792-7216 or Dr. Huong Le-Petross at 713-563-7827.