After neoadjuvant chemotherapy, axial ultrasound helps identify residual nodal disease – information that can guide the decision to pursue lymph node surgery, according to a report published online Feb. 2 in the Journal of Clinical Oncology.
This strategy of performing axial ultrasound to guide axillary surgery can reduce the number of both false-negative and false-positive results, thus improving both the rate of undertreating residual breast cancer and the rate of overtreating lymph nodes that have been cleared of the disease, said Dr. Judy C. Boughey of the Mayo Clinic, Rochester, Minn., and her associates.
They investigated two secondary end points of the American College of Surgeons Oncology Group Z1071 phase II clinical trial, which addressed sentinel lymph node surgery in women with initially node-positive breast cancer. The two end points were whether a normal appearance on ultrasound of sentinel lymph nodes after neoadjuvant chemotherapy denoted a decreased risk of residual cancer and whether an abnormal appearance of sentinel lymph nodes on ultrasound after neoadjuvant chemotherapy denoted an increased risk of residual cancer.
For this analysis of the ACSOG Z1071 data, Dr. Boughey and her associates assessed 611 study participants who initially had node-positive (stage T0-4, N1-2, M0) breast cancer treated at 136 medical centers, had completed neoadjuvant chemotherapy, had undergone axial ultrasound with archiving of the images, and had undergone sentinel lymph node surgery and axial dissection. A total of 70.4% of these patients had lymph nodes classified as normal on ultrasound and 29.6% had suspicious lymph nodes.
A total of 56.5% of patients with normal-appearing lymph nodes on ultrasound proved to have positive nodes on final pathology. In contrast, 71.8% – significantly more – of patients who had suspicious-looking lymph nodes on ultrasound proved to have positive nodes on final pathology (P less than .001). Women with suspicious nodal status on ultrasound also were more likely to have a higher number of positive nodes (34.5% vs 21.0%) and a larger median size of nodal metastases, representing a greater nodal disease burden, than those with normal appearance on ultrasound.
The investigators recommended a strategy in which patients with normal-appearing lymph nodes following adjuvant chemotherapy could undergo sentinel lymph node surgery. “If any of the sentinel lymph nodes were positive, the patient would undergo an axillary lymph node dissection, and if the sentinel lymph nodes were negative, then no further axillary surgery would be needed,” they wrote.
This approach yielded a false-negative rate of just 9.8% when applied to the Z1071 study population, compared with a 12.6% false-negative rate when axial ultrasound was not used to select patients for surgery. Any false-negative rate under 10% was predetermined to be acceptable when the study was designed, Dr. Boughey and her associates said (J. Clin. Oncol. 2015 [doi:10.1200/JCO.2014.57.8401]).
Among patients who had a normal node appearance on ultrasound but positive findings on sentinel lymph node surgery, 63% proved to have no additional positive nodes in the axillary lymph node dissection. “Therefore, in patients with normal axial ultrasound, sentinel lymph node surgery could be used to identify patients who may be able to avoid axillary lymph node dissection. This is being evaluated in the Alliance A11202 trial, which is currently enrolling patients and comparing axillary radiation to axillary dissection for patients with positive sentinel lymph nodes after neoadjuvant chemotherapy,” they added.
The ACOSOG Z1071 trial was supported by National Cancer Institute grants to the American College of Surgeons Oncology Group, the Alliance for Clinical Trials in Oncology, and the Alliance Statistics and Data Center. Dr. Boughey reported having no financial disclosures; one of her associates reported receiving research funding from Galena Biopharma and Antigen Express.