Less Is More Wins Again: Avoiding Node Dissection in Early Breast Cancer

SAN ANTONIO — Neoadjuvant chemotherapy that downstaged positive lymph nodes to negative led to a low rate of invasive breast cancer recurrence with either targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB), a large retrospective study showed.

The 3-year axillary recurrence rate was less than 1% with TAD or SLNB, while locoregional recurrence at 3 and 5 years was 1.5% and 2.7%, respectively, in all patients and did not differ significantly with the two strategies of limited nodal assessment.

The results provide additional evidence to support prior studies suggesting that patients with nodal downstaging after neoadjuvant therapy can safely avoid extensive axillary lymph node dissection (ALND), reported Giacomo Montagna, MD, of Memorial Sloan Kettering Cancer Center in New York City, during the San Antonio Breast Cancer Symposium.

“Our study is the first to compare outcomes after sentinel lymph node biopsy and TAD,” Montagna noted. “Early axillary recurrence after omission of axillary lymph node dissection in patients who start out as node positive and convert to node negative with neoadjuvant chemotherapy is a very rare event. It was not significantly lower with TAD than with sentinel lymph node biopsy, in spite of the fact that more TAD patients received nodal irradiation.”

“These results support omission of axillary lymph node dissection in patients who are successfully downstaged to node negative after neoadjuvant chemotherapy,” he added. “An ongoing prospective trial will provide insight into whether arm function and lymphedema rates differ after different staging procedures.”

Montagna pointed out that TAD allows for removal of fewer lymph nodes. Whether the difference is clinically meaningful and whether TAD is cost effective remain uncertain.

In response to a question from the audience, Montagna said that a total of four isolated axillary recurrences occurred, three in patients with HER2-positive breast cancer and one in a patient with triple-negative breast cancer (TNBC). Another attendee asked how the axillary recurrences were detected, but Montagna noted that such granular information was not available from a large retrospective study.

“I think the mode of detection of recurrences is an important issue, which is not described in many studies,” said Sheldon Feldman, MD, of Montefiore Medical Center in the Bronx, New York, in follow-up to Montagna’s response. “I do believe that many patients have subclinical axillary recurrences, which we don’t know about unless they progress and become large.”

“I think we know that in many patients with axillary disease, it remains relatively indolent and not important clinically,” he added. “I think this is an important factor for many of these studies looking at axillary recurrence, in terms of how the recurrences are detected.”

The results came from an analysis of 1,144 consecutive patients who had biopsy-proven T1-4 N1-3 breast cancer diagnosed from April 2013 to December 2020. All received neoadjuvant chemotherapy. The study population consisted of 666 patients who underwent SLNB and 478 who underwent TAD. Median follow-up was 4.2 years.

Records showed that 23% of the patients had HR-positive/HER2-negative disease, 54% had HER2-positive disease, and 23% had TNBC. All patients achieved pathologic downstaging, and 66% had pathologic complete response (ypT0/is).

Overall, the patients had a median of three sentinel lymph nodes removed (four in the SLNB group vs three with TAD, P<0.001). Median number of nodes removed was 4.4 with SLNB, 3.9 with TAD (P<0.001), and 4.2 overall. More patients in the TAD group received nodal irradiation (85% vs 78%, P=0.005) and adjuvant chemotherapy (8.6% vs 4.5%, P=0.005).

The two types of limited nodal assessment led to similar outcomes in all analyses:

• 3-year axillary recurrence: 0.5% with TAD vs 0.8% with SLNB
• 3-year locoregional recurrence: 0.8% vs 1.9%
• 3-year invasive recurrence: 7.8% vs 7.3%

Results at 5 years for both groups combined were 1.0% for axillary recurrence, 2.7% for locoregional recurrence, and 10.0% for invasive recurrence.

The study confirmed “what we already know” — that downstaging to ypN0 can allow patients to avoid ALND, said Anees Chagpar, MD, of the Yale Cancer Center in New Haven, Connecticut, who was not involved in the study. The lack of difference between TAD and SLNB is the more interesting finding, she noted.

“Certainly, others have shown a lower false-negative rate with TAD,” Chagpar, who is a member of the MedPage Today editorial board, wrote in an email. “What this study shows us is that this may not matter; for example in ACOSOG Z0011, avoiding ALND in sentinel lymph node-positive patients treated with primary surgery. We know that there should be other positive non-sentinel lymph nodes in 27% of patients, but we saw that this made no difference in terms of local recurrence.”

“So now, the question is, does microscopic disease matter and do we need to do more/bigger surgeries, or — in the current era of highly effective systemic therapy and radiation — is less surgery just as effective? Increasingly, whether we look at surgery for lymph nodes or even for the primary, we seem to be moving to a less [surgery]-is-more approach,” she noted.