Chipping Away at the Dogma of Axillary Dissection in Breast Cancer

MIAMI BEACH — The surgical dogma favoring axillary dissection in breast cancer continues to give way to more selective data-driven strategies that allow more women to avoid axillary surgery, an experienced breast surgeon said here.

A good case can already be made for omitting axillary surgery in women undergoing prophylactic mastectomy, patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery, and older women with early node-negative hormone receptor-positive (HR+) breast cancer. Several other clinical scenarios might be added to the list in the not-too-distant future, said Elizabeth Mittendorf, MD, of Dana-Farber Cancer Institute in Boston, during the Miami Breast Cancer Conference.

“We began by doing a lymph node dissection on every patient with breast cancer,” she said. “That evolved into doing sentinel node biopsy for those who are clinically node negative. Now we’re in an era where we’re doing sentinel node biopsy for clinically node-positive patients and for response to chemotherapy.

“My position is that we’re moving toward identifying additional clinical situations in which we can omit even sentinel node biopsy,” said Mittendorf.

The goals of axillary surgery are to improve survival and local control and to aid decisions about staging and treatment. No clinical trial to date has shown that axillary node dissection improves survival, said Mittendorf. More than 20 years ago, the NSABP B04 trial showed that axillary node dissection provided pathologic staging information, but no impact on survival. A succession of studies since then have shown no impact on axillary recurrence or survival.

Disease staging and treatment decision-making still present opportunities for critical evaluation about factors that influence breast cancer outcomes and the role of axillary surgery, she said.

Thinking about axillary surgery also has been influenced by changes in the broader clinical landscape of breast cancer. Key determinants of breast cancer outcome — disease burden, biology, and therapy — have changed dramatically in recent years.

Increased breast cancer screening has led to detection of earlier-stage disease and a reduction in nodal involvement, Mittendorf continued. Improved understanding of the biology of breast cancer, particularly molecular subtypes and the emergence of genomic risk assessment, have led to new treatment approaches. The proliferation of targeted therapies has been influenced by improved understanding of biology, which has also affected patient selection for neoadjuvant therapy.

“I think we can look at the question of how much axillary surgery is needed in the context of these multiple determinants of outcome,” said Mittendorf.

Available data already make a compelling case to omit axillary surgery in patients undergoing prophylactic mastectomy, particularly contralateral prophylactic mastectomy, which has a low prevalence of occult cancer. A decision-analysis study involving more than 500 patients undergoing prophylactic mastectomy showed that MRI-directed axillary lymph node dissection (ALND) decisions outperformed sentinel lymph node biopsy (SLNB) for allowing patients to avoid ALND.

“Only 1% of patients patients will be spared an axillary lymph node dissection by sentinel lymph node biopsy,” said Mittendorf. “Directed axillary node dissection was more effective than routine sentinel node biopsy. Modeling analysis showed that 36 patients without cancer would have been subjected to sentinel node biopsy to avoid one axillary node dissection.”

Axillary dissection also can be avoided for patients who have DCIS treated by lumpectomy, the rationale being that “we can go back and do a sentinel node biopsy from invasive disease identified in the lumpectomy specimen.” The rate of upgrade from DCIS to invasive disease is on the order of 20-25% in contemporary series, she said.

Finally, axillary dissection can be avoided in women ≥70 with early (cT1-2 N0) HR+ breast cancer. Support for the strategy came from a randomized trial reported almost a decade ago involving 600 patients randomized to lumpectomy plus tamoxifen with or without radiation therapy. Among almost 400 patients who had no axillary staging, the 10-year rate of axillary failure was 1.5%. The recommendation to skip ALND in low-risk older women has since found its way into the American Board of Internal Medicine Foundation’s Choosing Wisely campaign.

Looking ahead to other subgroups who might avoid ALND, Mittendorf offered four suggestions:

• DCIS with microinvasion (about 4% of patients will have a positive SLNB)
• Patients with cT1-2 N0 breast cancer
• Early node-negative HER2+ breast cancer or early triple-negative breast cancer treated with neoadjuvant chemotherapy (NAC)
• HR+/HER2- breast cancer with limited cN1 disease

“Ongoing trials are examining the omission of sentinel node biopsy in [cT1-2 N0], and I anticipate that we will get results from these trials probably in the next 2 or 3 years,” said Mittendorf. “The role of biology over anatomy in systemic therapy decisions is really what I think will drive the need for less sentinel node biopsy staging. High nodal pCR [pathologic complete response] rates in our clinically node-negative HER2-positive and triple-negative breast cancer patients who achieve a radiographic complete response and in-breast pCR suggests an opportunity to avoid post-NAC sentinel node biopsy.”