Intraoperative pathology evaluation during mastectomy may result in axillary overtreatment
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Key takeaways:
- Intraoperative pathology assessment led to increased use of both axillary lymph node dissection and axillary radiation.
- More judicious use of intraoperative pathology evaluation could reduce overtreatment.
Intraoperative assessment of sentinel lymph nodes during mastectomy significantly increased the likelihood of aggressive axillary treatment vs. postsurgical assessment of lymph node biopsies among certain women with breast cancer.
The findings, scheduled for presentation at American Society of Breast Surgeons Annual Meeting, suggest omission of routine intraoperative pathology assessment should be considered to minimize axillary overtreatment, according to researchers.
“Several clinical trials, including the AMAROS clinical trial, have established the safety of axillary observation or axillary radiation [AxRT] as an alternative to axillary lymph node dissection [ALND] in clinically node-negative [patients with breast cancer] found to have one to two positive sentinel lymph nodes,” Olga Kantor, MD, MS, breast surgical oncologist at Brigham and Women’s Hospital and Dana-Farber Cancer Institute and assistant professor of surgery at Harvard Medical School, said during a press briefing. “Mastectomy patients were included in these trials, but made up a minority of the trial population, ranging from about 9% to 18% of clinical trial participants. So, controversy remains in terms of the optimal axillary management.”
Avoiding overtreatment
Kantor said intraoperative pathology evaluation can be a valuable strategy that may obviate the need to return to the operating room for additional axillary surgery.
“However, acting on intraoperative pathology does not allow for multidisciplinary discussion,” Kantor said. “So, mastectomy patients who have their intraoperative pathology acted on and undergo ALND may still be recommended for postmastectomy radiation, and possibly the addition of AxRT. This dual approach may result in axillary overtreatment in patients [who] may otherwise have been eligible for axillary radiation alone.”
To analyze the impact of intraoperative pathology assessment in axillary management, Kantor and colleagues identified 40,467 patients in the National Cancer Database with AMAROS-eligible cT1-2N0 breast cancer who underwent upfront mastectomy between 2018 and 2019.
The researchers assessed patterns of axillary management based on the size of nodal metastases and use of intraoperative pathology. They categorized intraoperative pathology evaluation as “not done/not acted on” if axillary lymph node dissection had not been performed or occurred at a later date than sentinel lymph node biopsy, or as “done/acted on” if sentinel lymph node biopsy and ALND occurred on the same day. The researchers defined AxRT as postmastectomy radiation, “including radiation to the draining lymph nodes.”
“We examined axillary management by the use of intraoperative pathology assessment, and we also looked at predictors of receiving both ALND and axillary radiation, which may portend overtreatment in some patients in this population,” Kantor said.
Reconsidering intraoperative pathology
Of the 40,467 AMAROS-eligible patients, 8,222 met all of the study criteria, including having tumors up to 5 cm that were clinically node-negative on presentation and one to two positive sentinel lymph nodes.
In 5,159 (62.8%) cases, intraoperative pathology was not done/not acted upon and in 3,057 (37.2%) cases it was done/acted upon. About one-third of patients (32.7%) underwent observation as the overall axillary management approach, whereas 26.3% underwent ALND, 22.7% received AxRT and 18.4% had both ALND and AxRT.
About 41% of women underwent treatment with both ALND and AxRT after intraoperative evaluation of pathology, compared with only 4.9% who underwent postoperative pathology evaluation and decision-making (P < .001). Among patients whose intraoperative pathology was not done/not acted on, 609 (11.8%) subsequently returned to undergo ALND.
“We found that compared [with] patients who did not have intraoperative pathology acted on, those who did have intraoperative pathology were more likely to have larger tumors and lymph vascular invasion,” Kantor said. “They also had a higher proportion of having two vs. one positive sentinel lymph nodes and they were also more likely to have sentinel lymph node macrometastases.”
Multivariate analysis adjusting for patient and tumor characteristics found use of intraoperative pathology evaluation and real-time axillary decision-making to be the strongest predictor of treatment with both ALND and AxRT (OR = 8.99; 95% CI, 7.7-10.5). Other predictive factors included macrometastases (OR = 3.38; 95% CI, 2.63-4.33) and number of total positive nodes (two, OR = 2.14; three, OR: 3.92; more than three, OR: 5.31).
“Over the timeframe of our study, we found that not performing or acting on intraoperative pathology in this population led to about a 36% reduction in receiving both ALND and AxRT, and intraoperative pathology was by far the strongest predictor of receiving both,” Kantor said. “We feel these results suggest that consideration should be made for omission of routine intraoperative pathology assessment to minimize overtreatment with both ALND and AxRT in appropriate patients who may have received axillary radiation therapy alone.”
Perspective
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Julie E. Lang, MD, FACS
Pride, Kantor and colleagues used the National Cancer Database to perform an analysis of AMAROS-eligible patients undergoing upfront mastectomy for cT1-2N0 invasive breast cancer using the National Cancer Database.
Omitting or not acting on intraoperative pathology frozen section analysis led to significant reductions in rates of receiving treatment with both axillary lymph node dissection (ALND) and nodal irradiation. Not surprisingly, researchers observed differences in the proportion of patients with more nodal involvement in the group undergoing intraoperative pathology, since intraoperative pathology was associated with ALND.
Studies have consistently shown that the more we resect and examine lymph nodes, the more disease we may find, but this does not improve survival or quality of life for patients with breast cancer.
I applaud the authors’ conclusion that consideration should be made for omission of intraoperative pathology to minimize axillary overtreatment. This approach already has been adopted by my institution’s multidisciplinary breast cancer team since the 10-year follow-up results for AMAROS showed no difference in axillary recurrence rates.
At our institution, if a patient with cT1-2 disease is found to be unexpectedly node positive on permanent histopathology, our multidisciplinary team discusses if ALND is warranted. For patients planned for ALND, we consider if they are a candidate for lymphovenous bypass (LVB) with axillary reverse lymphatic mapping (ARM). This delayed ALND strategy allows us time to plan the logistics of ALND, ARM and LVB in order to plan a combined case together with a microvascular-trained plastic surgeon, if the patient wishes to pursue this option after an unexpected finding of nodal positivity. Alliance A221702 will address if ARM can help reduce the rates of lymphedema. Our institution and many others are investigating the question of whether LVB can reduce rates of lymphedema after ALND.
Surgeons are well on their way toward de-escalating axillary surgery, as seen by the reduction in rates of ALND in recent years among patients who underwent lumpectomy or mastectomy. It is not necessary to do a clinical trial of omission of frozen section of axillary lymph nodes in clinically node-negative mastectomy patients in light of the 10-year AMAROS results that had a very low axillary recurrence rate in node-positive patients treated by sentinel node alone. As shown by Pride, Kantor and colleagues, surgeons should omit checking frozen section for AMAROS-eligible patients.
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Pride R, et al. Intraoperative pathology assessment may lead to overtreatment of the axilla in clinically node-negative breast cancer patients undergoing upfront mastectomy. Presented at: American Society of Breast Surgeons Annual Meeting; April 26-30, 2023; Boston.
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