From routine axillary lymph node dissection to sentinel lymph node surgery, the use of axillary surgery continues to evolve in breast cancer. Recently, surgical oncologists have begun to consider avoiding axillary surgery completely in patients with a low risk of node-positive disease as well as in those for whom axillary status does not impact disease management.
During the 2021 American Society of Breast Surgeons (ASBrS) Annual Meeting, Judy C. Boughey, MD, FACS, Professor of Surgery and Chair of Breast and Melanoma Surgical Oncology at Mayo Clinic, Rochester, discussed de-escalating axillary surgery, including cases where axillary surgery can be avoided altogether and cases where it can be limited to sentinel lymph node surgery.1
“This is a very exciting time for us to be able to individualize our treatment, taking into account both patient and tumor factors,” said Dr. Boughey. “We need to consider the impact of systemic therapy on our surgical options, and we need to consider the impact of our surgical options on adjuvant treatment recommendations.”
Judy C. Boughey, MD, FACS
Axillary Surgery in DCIS
Although ductal carcinoma in situ (DCIS) does not metastasize and patients do not die from the disease, Dr. Boughey reported that approximately 20% of patients undergoing breast-conserving surgery who are found to have pure DCIS on final pathology still undergo sentinel lymph node surgery, with the removal of one to five lymph nodes. Furthermore, said Dr. Boughey, 80% of women undergoing mastectomy for pure DCIS have between one and five lymph nodes removed.
“This is definitely an area of ongoing overtreatment and an opportunity for us to de-escalate further in the future,” said Dr. Boughey. “Sentinel lymph node surgery should be limited to patients most likely to have invasive disease—those who present with a palpable mass, have extensive DCIS over an area of more than 5 cm, or already have microinvasion on their biopsy.”
The availability of superparamagnetic iron oxide nanoparticles could help with de-escalation in this setting. In the SentiNot study, 189 patients with DCIS at risk of upstaging to invasive disease underwent preoperative injection of superparamagnetic iron oxide nanoparticles.2 Of these patients, 47 were upstaged to invasive disease on final pathology, and 40 of these 47 underwent delayed sentinel lymph node surgery. A total of 78.3% of patients undergoing surgery, however, were able to avoid sentinel lymph node dissection. In the study, avoiding routine sentinel lymph node surgery in patients who do not need this additional surgery allowed them to decrease the overall cost of care by about 25%.
Axillary Surgery in Women Older Than 70
In women over age 70 with hormone receptor–positive disease who are clinically node-negative, Choosing Wisely guidelines (issued by the Society of Surgical Oncology) recommend against routine sentinel lymph node surgery. Dr. Boughey and colleagues have looked to further stratify these patients into low-risk and higher-risk groups. Patients with grade 1 disease up to 2 cm in diameter or grade 2 disease up to 1 cm, for example, have a rate of nodal positivity of approximately 7.8%.3 Patients who do not meet these low-risk criteria, on the other hand, have a threefold higher rate of nodal positivity (more than 22%).
“In women with small, low-grade disease, we should forgo sentinel lymph node surgery in this setting,” said Dr. Boughey. “In patients who do not meet the low-risk criteria, we still need to be very cautious about the role for sentinel node surgery and do this only on a case-by-case basis, depending on the patient’s comorbidities and how this nodal information may impact their adamant treatment recommendations.”
Axillary Surgery in Breast-Conserving Therapy
In patients with one to two positive sentinel lymph nodes who are treated with breast-conserving surgery and whole-breast radiation therapy, 10-year follow-up data from the ACOSOG Z0011 trial showed no difference in recurrence or survival data with forgoing axillary lymph node dissection.4 According to Dr. Boughey, this study has been practice-changing and has been implemented well across institutions, with some sites showing a decrease in axillary lymph node dissection from 85% prior to publication of the study to 8% in 2016.
Patients with triple-negative or HER2-positive breast cancer and a clinically node-negative presentation who are treated with neoadjuvant chemotherapy and achieve a breast pathologic complete response could potentially avoid axillary surgery altogether.— Judy C. Boughey, MD, FACS
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The more controversial question, said Dr. Boughey, is whether axillary lymph node dissection can be avoided in patients undergoing mastectomy with one to two positive sentinel lymph nodes. Prospective data from the AMAROS trial and the IBCSG 23-01 trial demonstrated that complete axillary lymph dissection does not, in fact, provide an advantage in this patient population.5,6
“For patients at intermediate risk, meaning one or two positive sentinel lymph nodes, we would consider either axillary lymph node dissection or axillary radiation, but really try to avoid putting that patient at risk of having both axillary radiation and surgery,” said Dr. Boughey. “For patients who don’t have an indication for postmastectomy radiation, I would favor axillary lymph node dissection, with the goal of trying to avoid radiation. For those who do require postmastectomy radiation, however, it is prudent to consider omitting axillary lymph node dissection to avoid overtreatment.”
Patients in the highest risk category (ie, three or more positive nodes or more extensive disease) should be treated with both surgical resection and nodal radiation, Dr. Boughey said.
Axillary Surgery After Neoadjuvant Chemotherapy
Neoadjuvant chemotherapy use is increasing, especially in patients with triple-negative and HER2-positive breast cancer, and this can allow downstaging of axillary lymph nodes. “For patients who present with node-positive disease and have a good response to neoadjuvant chemotherapy, sentinel lymph node surgery provides a reasonable staging method to identify those who have successfully had their nodal disease eradicated, which allows them to forgo the morbidity of an axillary lymph node dissection,” said Dr. Boughey. “This allows us to tailor our surgery based on response to therapy, just as we do in the breast.”
Dr. Boughey reported high rates of nodal pathologic complete response for patients with triple-negative breast cancer (50% or higher) and HER2-positive disease (65% or higher). “These nodal pathologic complete response rates should only increase as we see improvements in our selection of patients for systemic therapy and in our options for systemic and targeted therapy,” she said.
Several ongoing clinical trials are looking at further de-escalation in this setting. The ALLIANCE A11202 study is randomly assigning patients who are sentinel node–positive after neoadjuvant chemotherapy to axillary dissection vs no further axillary surgery, whereas the B-51/RTOG 1304 study is randomly assigning patients with eradicated disease who are node-negative on final pathology to radiation vs no radiation.
“Pending the results of B-51, we can potentially avoid nodal radiation in patients who convert from node-positive to node-negative,” said Dr. Boughey. “Pending results of A11202, we can potentially substitute axillary dissection with definitive nodal radiation in patients who have pathologic residual nodal disease.”
Avoiding Axillary Surgery After Neoadjuvant Chemotherapy
According to Dr. Boughey, there is one subgroup of patients for whom axillary surgery may no longer be needed after completion of neoadjuvant chemotherapy: patients who have eradication of disease based on imaging. A feasibility trial at The University of Texas MD Anderson Cancer Center looked at breast pathologic complete response, which has higher rates in patients with triple-negative disease or HER2-positive disease.7 As Dr. Boughey reported, patients who achieved complete eradication of the disease in the breast and were clinically node-negative at their initial presentation with breast cancer had an extremely low rate of being pathologically node-positive after surgery (less than 2%).
“Patients with triple-negative or HER2-positive breast cancer and a clinically node-negative presentation who are treated with neoadjuvant chemotherapy and achieve a breast pathologic complete response could potentially avoid axillary surgery altogether,” said Dr. Boughey. “Obviously, this will be dependent on reliably identifying preoperatively which of those patients achieve a breast pathologic complete response.”
DISCLOSURE: Dr. Boughey has received institutional research support from Lilly.
REFERENCES
1. Boughey JC: De-escalating therapy: Surgical therapy. 2021 ASBrS Virtual Annual Meeting. Presented April 30, 2021.
2. Karakatsanis A, Hersi AF, Pistiolis L, et al: Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study). Br J Surg 106:720-728, 2019.
3. Welsh JL, Hoskin TL, Day CN, et al: Predicting nodal positivity in women 70 years of age and older with hormone receptor-positive breast cancer to aid incorporation of a Society of Surgical Oncology Choosing Wisely guideline into clinical practice. Ann Surg Oncol 24:2881-2888, 2017.
4. Giuliano AE, Ballman KV, McCall L, et al: Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA 318:918-926, 2017.
5. Donker M, van Tienhoven G, Straver ME, et al: Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): A randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol 15:1303-1310, 2014.
6. Galimberti V, Cole BF, Zurrida S, et al: Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): A phase 3 randomised controlled trial [erratum in Lancet Oncol 14(7):e254, 2013]. Lancet Oncol 14:297-305, 2013.
7. Kuerer HM, Rauch GM, Krishnamurthy S, et al: A clinical feasibility trial for identification of exceptional responders in whom breast cancer surgery can be eliminated following neoadjuvant systemic therapy. Ann Surg 267:946-951, 2018.
