PerspectiveIn the Journals

New surgical technique improves staging accuracy of node-positive breast cancer

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February 2, 2016

Targeted axillary dissection appeared to improve the accuracy of axillary staging and pathologic evaluation of node-positive breast cancer, according to prospective study results.

This new surgical technique may spare patients from undergoing complete axillary lymphadenectomy, a more invasive procedure associated with significant morbidity.

Abigail Caudle, MD

Abigail S. Caudle, MD

Targeted axillary dissection — developed by surgeons at The University of Texas MD Anderson Cancer Center — involves the removal of sentinel lymph nodes and other cancerous nodes that were clipped at diagnosis.

The standard of care for clinically node-positive patients is axillary lymphadenectomy; however, this procedure is associated with potential lifelong implications such as numbness and debilitating lymphedema.

The addition of neoadjuvant chemotherapy prior to surgery has previously shown that about 40% of patients have no nodal metastases, and therefore may be able to forgo axillary lymphadenectomy.

“As chemotherapy is utilized more often before surgery, there is a greater likelihood that the disease in the lymph nodes will be eradicated and surgeons do not need to perform extensive nodal surgery,” Abigail S. Caudle, MD, assistant professor of breast surgical oncology at MD Anderson, said in a press release.

However, surgeons have not had a way to identify women who have had such a nodal change following chemotherapy, which has led to a regular use of the axillary lymphadenectomy, she said.

Sentinel lymph node dissection can serve as an alternative, but that procedure often leads to false-negative results, missing the presence of residual disease in up to 15% of women.

“We just haven’t had a good way to determine which patients have converted to node-negative status and, thereby, we are subjecting too many women to unnecessary surgery,” Caudle said in the release. “We hoped to find a new way to target the lymph node known to have cancer, selectively remove it, look at it, and hopefully avoid additional surgery if chemotherapy has wiped out all the cancer.”

The researchers enrolled 208 patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node between 2011 and 2015. Following neoadjuvant chemotherapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes.

The surgical approach was then determined by a surgical oncologist. Those undergoing targeted axillary dissection received a sentinel lymph node dissection and selective removal of the clipped node using iodine-125 seed localization. If patients underwent complete axillary lymphadenectomy, researchers used these data to calculate a false-negative rate.

A total of 191 women underwent an axillary lymphadenectomy, 63% of whom (n = 120) had detectable residual disease. Evaluation of the clipped node showed there were metastases in 115 patients, which resulted in a false-negative rate for axillary lymphadenectomy of 4.2% (95% CI, 1.4-9.5).

One hundred eighteen women underwent sentinel lymph node dissection and an axillary lymphadenectomy. In this cohort, there were seven false-negative events and 69 patients with residual disease, equating to a false-negative rate of 10.1% (95% CI, 4.2-19.8).

However, when the researchers added the evaluation of the clipped node, the false-negative rate reduced to 1.4% (95% CI, 0.03-7.3). In 23% of the patients (n = 31), the clipped node was not removed as a sentinel lymph node. This included six women with a negative sentinel lymph node but metastasis in the clipped node.  

Eighty-five patients underwent targeted axillary dissection followed by an axillary lymphadenectomy in 85 patients, which was associated with a false-negative rate of 2% (95% CI, 0.05-10.7).

As a result of these findings, MD Anderson has changed its guidelines for care at their institution. Women with three or fewer involved lymph nodes at presentation may be offered the targeted axillary dissection in the hopes of avoiding axillary lymphadenectomy.

Additionally, researchers will continue to study whether the procedure can potentially be offered to patients with more advanced axillary disease.

“This study may now allow up to 40% of women who are diagnosed with axillary metastasis and undergo neoadjuvant chemotherapy to avoid more extensive and often debilitating surgery,” Henry M. Kuerer, MD, PhD, study researcher and professor of breast oncology at MD Anderson, said in the release. “Our findings epitomize precision surgery in that we are specifically targeting the known disease and limiting the morbidity for our patients.” – by Anthony SanFilippo

Disclosure: Caudle reports no relevant financial disclosures. Kuerer reports consultant/advisory roles with Gerson Lehrman Group and Lightpoint Medical, as well as research funding from Genomic Health. Please see the full study for a list of all other researchers’ relevant financial disclosures.

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PERSPECTIVE
Anees B. Chagpar, MD, MSc, MBA, MA, MPH, FACS, FRCS(C)

Anees B. Chagpar, MD, MSc, MBA, MA, MPH, FACS, FRCS(C)

The study by Caudle and colleagues from The University of Texas MD Anderson Cancer Center describing a new technique to reduce the false-negative rate of sentinel node biopsy after neoadjuvant chemotherapy is intriguing, but there are a few issues worth considering.

Although the reduction in false-negative rate from 10.1% to 1.4% with evaluation of the clipped node is impressive, one wonders whether this will have true clinical impact. 

The authors of this study defined a positive node as any tumor deposit — including isolated tumor cells — but data are limited in terms of the clinical significance of such disease.  Further, in the current era of multidisciplinary management, one would expect nearly all of these patients will receive adjuvant radiation therapy. 

Given this, one wonders whether reducing minimal residual disease in the axilla would truly translate into lower locoregional recurrence rates. There are data outside the neoadjuvant setting demonstrating that leaving disease behind in the axilla in patients with node-positive disease does not result in worse long-term outcomes. Although data are lacking in the neoadjuvant setting, it would not be a stretch to imagine that the same would hold. Hence, in our quest to find techniques to lower the false-negative rate for sentinel node biopsy after neoadjuvant therapy — particularly using a definition of any tumor cell being a positive node — are we only increasing the number of patients undergoing an axillary node dissection with all of its morbidity without data to suggest that this will truly be of long-term benefit for our patients? 

Finally, one has to wonder about the cost and feasibility of the targeted axillary dissection (TAD) procedure. This would involve fine needle aspiration of enlarged lymph nodes, cytological examination of the same, placement of a clip in the node, followed by an I-125 seed placement under ultrasound guidance 1 to 5 days prior to surgery, and the equipment to detect this frequency in the operating room (which is not on all commonly used gamma probes). Without evidence that the reduction in false-negative rates for sentinel node biopsy results in improvements in long-term recurrence rates or DFS, one must question the value of this technique that will undoubtedly add cost.

The false-negative rate of sentinel node biopsy after neoadjuvant therapy has been higher than most surgeons would like, and certainly many will use dual tracers and aim to remove more than three nodes in an effort to reduce this. This study provides a technique that dramatically reduces the false-negative rate of sentinel node biopsy in this setting. The only question that remains is, does it matter?


Anees B. Chagpar, MD, MSc, MBA, MA, MPH, FACS, FRCS(C)
Yale University

Disclosure: Chagpar reports no relevant financial disclosures.