ASCO Guidelines Support Sentinel Node Biopsy for Early-Stage Breast Cancer

Blue stained lymph nodes removed through small incision

New guidelines supporting the broader use of sentinel lymph node biopsy in women with early-stage breast cancer have been issued by the American Society of Clinical Oncology (ASCO). The guidelines were published in the Journal of Clinical Oncology.

ASCO recommends the use of sentinel node biopsy in most patients, rather than the more invasive axillary lymph node dissection, which is linked to a higher risk of complications.

The initial guidelines were published in 2005. The guideline committee included medical oncologists, pathologists, radiation oncologists, and surgical oncologists, as well as guideline implementation and advocacy experts.

The current update now adds evidence from 9 randomized studies and 13 cohort studies demonstrating that sentinel node biopsy is appropriate for many early-stage breast cancer patients after a review of the applicable literature published from 2004 to 2013. The guidelines can help clinicians determine which patients can receive a sentinel node biopsy and which patients need an axillary lymph node dissection.

Summary of the Updated Recommendations Based on Randomized Trials:

• Women who do not have metastases in the sentinel lymph node should not receive axillary lymph node dissection.

• Women who have 1–2 metastatic sentinel lymph node(s) and plan to have breast-conserving surgery with whole-breast radiotherapy should not undergo axillary lymph node dissection in most cases.

• Women with sentinel lymph node metastases who will undergo mastectomy should be offered axillary lymph node dissection.

Summary of the Updated Recommendations Based on Cohort Studies and Committee Informal Consensus:

• Women with operable breast cancer and multicentric tumors, with ductal carcinoma in situ (DCIS), who will undergo mastectomy and who previously underwent breast and/or axillary surgery or received preoperative or neoadjuvant systemic therapy may be offered sentinel lymph node biopsy.

• Women who have large tumors (tumor size T3/T4), locally advanced invasive breast cancer, or DCIS (when breast-conserving surgery is planned) or those who are pregnant should not undergo sentinel lymph node biopsy.

To address the question of whether axillary lymph node dissection should be avoided in patients who have tumor-free sentinel nodes, the committee reviewed seven prospective randomized clinical trials, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial, the Axillary Lymphatic Mapping Against Nodal Axillary Clearance (ALMANAC) trial, and the Sentinella/GIVOM (Gruppo Interdisciplinare Veneto di Oncologia Mammaria) trial. The results from these trials included data on overall survival, recurrence, adverse events, technical success, and performance, as well as morbidities and quality of life.

Five of these seven trials reported clinical efficacy, and none showed a statistically significant difference in overall survival or mortality in those women who had a sentinel node biopsy compared with axillary lymph node dissection. The largest study, the B-32 clinical trial, showed an 8-year survival rate of 91.8% for sentinel node biopsy and axillary lymph node dissection compared with 90.3% sentinel node biopsy alone. The all-cause mortality was 4% in each arm.

Adverse events, reported in five of the seven trials, showed higher rates in those with tumor-free sentinel node biopsies who then had an axillary lymph node dissection compared with those who only had a sentinel node biopsy. Adverse events included lymphedema, infections, seroma, and neurologic and sensory deficits such as paresthesia, shoulder pain, and impairment of motion.

Sentinel node biopsy has been an important advancement in improving the quality of life of breast cancer patients, according to the guidelines committee. The sentinel node is the first node to show the presence of cancer as the cancer spreads through the lymphatic system. In sentinel node biopsy, only a few lymph nodes are removed and analyzed for the presence of cancer. No evidence of cancer in the sentinel node typically means that the remaining nodes are also cancer-free. Axillary lymph node dissection is the removal of most lymph nodes under the arm on the same side as the breast tumor and analysis of these nodes for cancer spread. Unlike the sentinel node biopsy, axillary lymph node dissection has a higher risk of long-term side effects.

Four studies reported on lymphedema, showing that this side effect occurred in those who had a sentinel node biopsy, but less frequently than in those women who had an axillary lymph node dissection. For example, in the ALMANAC trial, lymphedema (measured by patients’ self-assessment) occurred in 1% of those who had a sentinel node biopsy and in 2% of those who underwent an axillary lymph node dissection (P < .001).

“We strongly encourage patients to talk with their surgeon and other members of their multidisciplinary team to understand their options and make sure everybody is on the same page,” said Gary Lyman, MD, co-chair of the panel and clinician at the Fred Hutchinson Cancer Research Center in Seattle, in a statement. “The most critical determinant of breast cancer prognosis is still the presence and extent of lymph node involvement and, therefore, the lymph nodes need to be evaluated so we can understand the extent of the disease.”

“It is essential that surgeons and pathologists and nuclear medicine doctors at an institute that offers sentinel node biopsy be trained and experienced in the technique and demonstrate proficiency in accurate identification of the sentinel node(s) with a minimal complication rate,” said Dr. Lyman. “Injection of both radioisotope and blue dye for sentinel node identification are commonly used. The value of other techniques that enhance sentinel node identification varies and they are less standardized. Likewise, processing of the lymph node samples and pathology assessment of the sentinel node have been fairly standardized and are discussed in some detail in the guideline.”

According to Lyman, the American College of Surgeons Oncology Group Z0011 trial was particularly instrumental in assuring the panelists that many women who have one or two positive nodes on a sentinel node biopsy do not require an axillary lymph node dissection, as was previously recommended. This new recommendation applies to women who do not have extensive involvement of the affected lymph nodes, have relatively small primary tumors, and have not received neoadjuvant chemotherapy. Additionally, only those patients who are having breast-conserving surgery after locoregional radiation therapy are recommended to forego axillary lymph node dissection, said Lyman. If a full mastectomy is planned, then the patient should still undergo axillary lymph node dissection if the sentinel node biopsy is positive.

“Much more research is needed to better define special circumstances when sentinel node biopsy alone may replace the need for full axillary lymph node dissection, such as in pregnant patients, many patients with DCIS, and those with inflammatory breast cancer,” said Lyman. Other still unanswered questions are the maximum size of the primary tumor at which point a sentinel node biopsy is no longer adequate to evaluate the risk of axillary lymph node involvement, as well as the role of sentinel node biopsy in patients receiving neoadjuvant chemotherapy.