Kelly K. Hunt, MD
Twenty-five years ago, breast cancer clinical trials examined whether neoadjuvant therapy—prior to surgery—was as safe as adjuvant therapy. “There was a lot of concern that if the patient progressed on therapy, you would lose the opportunity to operate,” said Kelly K. Hunt, MD, professor of surgical oncology at the MD Anderson Cancer Center in Houston, Texas.
Hunt discussed the management of the axilla after neoadjuvant chemotherapy at the 32nd Annual Miami Breast Cancer Conference. OncLive
spoke with Hunt before the conference about how breast cancer interventions have progressed in the adjuvant and neoadjuvant setting and about the role of sentinel lymph node dissection (SLND) in the neoadjuvant setting.
These earlier trials, which did not distinguish between the breast cancer subtypes—estrogen-receptor positive (ER+), triple negative, and HER2 positive—established that neoadjuvant chemotherapy allows for more patients to undergo breast-conserving surgery rather than mastectomies. Metaanalyses that compared adjuvant to neoadjuvant systemic therapies showed no difference in disease progression, distant disease recurrence, or death from breast cancer, and also showed that neoadjuvant chemotherapy had fewer side effects.1,2
Subsequent studies examined whether a pathological complete response (pCR) following neoadjuvant therapy is a valid surrogate endpoint for longer-term outcomes, such as disease-free survival (DFS) and overall survival (OS). Many of these trials provided evidence that pCR does translate to better OS, but meta-analyses could not confirm that pCR translated into improved OS.3
“Partly, this is because we now understand that when breast cancers are divided into subtypes, patients with ER-negative and HER-positive disease are more likely to have a pCR from neoadjuvant therapy compared with those with ER-positive disease,” said Hunt.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocols B-18 and B-27 have demonstrated that stacking two chemotherapies in the neoadjuvant setting in women with operable breast cancer results in DFS and OS similar to adjuvant chemotherapy.4
Now, neoadjuvant studies have moved beyond the neoadjuvant-versus-adjuvant-therapy question to ask which neoadjuvant regimens are optimal for each breast cancer subtype to improve pCR, according to Hunt.
“We have learned that not only are we getting more patients to breast conservation, but that we’re getting more patients to node-negative disease following surgery, even when patients started with biopsy-proven node-positive disease,” Hunt said. She mentioned that this holds true for all breast cancer subtypes, but particularly for women with HER2-positive disease, as a result of available HER2-directed therapies.
One study conducted at MD Anderson of 109 patients with HER2-positive node-positive disease demonstrated a 74% (81 patients) axillary pCR after trastuzumab-containing neoadjuvant chemotherapy followed by breast surgery and complete axillary lymph node dissection.5
“This was a single-institution study, but others and also the NSABP B-27 and B-18 studies have shown that when you compare patients that were treated with neoadjuvant and adjuvant systemic therapies, there are fewer node-positive patients in the neoadjuvant compared to the adjuvant groups.”
The National Comprehensive Cancer Network guidelines currently list appropriate neoadjuvant therapy options for women with breast cancer based on subtype. “Neoadjuvant therapy is considered for those patients that have at least T2 disease or node-positive disease,” said Hunt. “Some physicians also consider neoadjuvant therapy for small HER2-positive tumors between 1 and 2 centimeters in size.”Less Axillary Surgery?
“Neoadjuvant therapy is a powerful way to assess response and to help clinicians understand a patient’s prognosis based on residual tumor burden and disease in the lymph nodes,” said Hunt. “The most proven benefit of neoadjuvant systemic therapy is less subsequent surgery.” The neoadjuvant approach has been established; the question now emerging is whether a targeted axillary node dissection, rather than a full axillary dissection, is as accurate and whether it leads to similar outcomes.
Axillary node dissection removes the entire axillary fat pad, which contains between 15 and 20 lymph nodes in the arm pit. These nodes are then assessed by a pathologist. Sentinel lymph node dissection removes one to three lymph nodes and is the standard way to stage breast cancer in patients with clinically lymph node–negative disease. Typically, women are assessed for lymph node disease at diagnosis with a physical examination and ultrasound.