Therefore, in patients with early-stage breast cancer undergoing whole breast radiation, ASCO guidelines have always advised against performing complete lymph node dissection routinely with either negative or one to two positive axillary sentinel lymph nodes. In practice, this dogma has been reaffirmed by the survival and disease-free outcomes of several clinical trials and reviews between 2012 and 2016. In fact, this concept has been demonstrated in recent trials in patients with micrometastatic nodal disease (IBCSG 23-01) as well as in patients treated with axillary radiation (AMAROS study). Indeed, in our experience, omission of axillary lymph node dissection is an important consideration for women who meet the clinical criteria, as it can promote quality of life and avoid complications such as lymphedema.
However, there are instances where these guidelines may need to be interpreted with caution, particularly in risky patients with primary tumors greater than 5 cm, bulky axillary sentinel lymph nodes, and gross extranodal extension of tumor. Moreover, the data from Z0011 should not be extrapolated to women who undergo neoadjuvant chemotherapy, who may have a higher risk for refractoriness to systemic therapy, or to women who undergo mastectomy, who are not treated with radiation as was performed in the actual trial.
Regarding sentinel lymph node biopsy, we typically offer this to operable patients who undergo mastectomy, have multicentric disease, DCIS, had prior breast/axillary surgery, or who received neoadjuvant chemotherapy. However, there are also instances where this should not be performed, including inflammatory breast cancer, DCIS, breast-conserving surgery, pregnancy, and patients with T3 or T4 early-stage cancer.
In summary, we have gained valuable experience with subsequent clinical studies since the Z0011 trial, confirming the concept that axillary lymph node dissection can be excluded in patients with early-stage breast cancer undergoing whole breast radiation, with one to two positive axillary sentinel lymph nodes. In clinical practice, it is important to ensure that our patients spared of axillary dissection meet the clinical criteria for this exclusion, while being wary of the features that may still warrant its inclusion.
Recent recommendations from the American Society of Clinical Oncology reaffirm a conservative approach to sentinel lymph node biopsy in patients with early stage breast cancer.
New evidence supports the "less is more" approach initially recommended in a 2014 ASCO guideline that advised against routine axillary lymph node dissection in the presence of cancer in a sentinel node.
The most recent recommendations are consistent with those previous recommendations, the guidelines committee, led by Gary H. Lyman, MD, MPH, co-director of the Hutchinson Institute for Cancer Research Outcomes at Fred Hutchinson Cancer Research Center in Seattle, wrote in the Journal of Clinical Oncology. Similar to the situation with the 2014 recommendations, "the Update Committee advises that axillary lymph node dissection can be avoided in patients with one or two positive sentinel nodes only when conventionally fractionated whole-breast radiation therapy is planned. Clinicians should also consider this recommendation with caution in patients with large primary tumors (>5 cm), those with large or bulky metastatic axillary sentinel lymph nodes, and/or those with gross extranodal extension of the tumor."
The reiteration of the 2014 recommendations was the result of analysis of eight randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guidelines released from 2012 through July 2016. Of the eight publications identified and reviewed, "none prompted a change in the 2014 recommendations, which are reaffirmed by the updated literature review," the committee wrote.
The American College of Surgeons Oncology Group (ACOSOG) Z0011 randomized clinical trial, published in 2010/2011, showed that in women with clinically node-negative, T1-T2 breast cancer treated with breast-conserving therapy and found to have metastases in one or two sentinel lymph nodes, sentinel lymph node dissection alone did not compromise local-regional control, disease-free survival (DFS), and overall survival (OS) compared with axillary lymph node dissection.
Women with operable breast cancer and multicentric tumors, with ductal carcinoma in situ, who will undergo mastectomy, who previously underwent breast and/or axillary surgery, or who received preoperative/neoadjuvant systemic therapy may be offered sentinel node biopsy.
Sentinel node biopsy should not be performed in women who have early-stage breast cancer with large or locally advanced invasive breast cancers (tumor size T3/T4). Sentinel node biopsy should also be omitted when the patient has inflammatory breast cancer, ductal carcinoma in situ, and planned breast-conserving surgery, or when the patient is pregnant.
For patients with a negative sentinel lymph node, the omission of axillary lymph node dissection does not adversely affect disease-free survival, overall survival, or local-regional control.
Although the guidelines seem to have been embraced within academic centers and larger hospitals and cancer centers, compliance is variable elsewhere, Lyman added, noting that many surgeons in the U.S. are still routinely performing full lymph node dissections on patients.
There is a concern that surgeons may be extrapolating the recommendations to populations that did not meet the ACOSOG Z0011 trial eligibility criteria or who did not undergo study-specific treatment, said Elizabeth Mittendorf, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston. Specifically, there is general agreement that the Z0011 data should not be applied to women undergoing mastectomy because many women who receive mastectomy are not treated with radiation, which may contribute to the favorable outcome in Z0011.
"Similarly, there are individuals who are extrapolating the data to patients who receive neoadjuvant chemotherapy, and that's a completely different patient population that has somewhat demonstrated themselves to be refractory to systemic therapy if they still have residual nodal disease," she told MedPage Today.
Mittendorf cited a paper by Katherine Yao et al in the Journal of the American College of Surgeons, in which the authors found that about 22% of patients undergoing mastectomy and found to have one or two positive sentinel lymph nodes did not undergo axillary lymph node dissection, suggesting broader extrapolation of the Z0011 trial results.
Data from the IBCSG 23-01 trial suggest that axillary lymph node dissection can be safely omitted in clinically node-negative patients undergoing mastectomy and found to have micrometastatic nodal disease, Mittendorf noted. In addition, the AMAROS study, which enrolled patients who were similar to those in Z0011 (clinical T1-T2, N0 disease), randomized patients with a positive sentinel lymph node to have axillary lymph node dissection or axillary radiation. The results found no differences in the 5-year rates of axillary recurrence, DFS, or OS between the groups, but patients randomized to axillary radiation had significantly less lymphedema.