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Guidelines Promote Use of Sentinel Node Biopsy in Breast Cancer

Caroline McNeil

The use of sentinel node biopsy (SNB) in breast cancer has spread rapidly. Eight years ago, the percentage of breast cancer patients at five major cancer centers who had SNBs was 13%. Just 3 years later, it was 57%. And today, the staging procedure—in which the first, or sentinel, axillary lymph node to which breast tissue drains is sampled to determine whether tumor cells have spread beyond the breast—is practically universal.

"SNB is routinely used in place of axillary dissection by virtually all surgeons that do any volume of breast cancer," said Stephen Edge, M.D., of Roswell Park Cancer Center, Buffalo, N.Y., who led the five-center study. Edge and other experts agree that SNB is now the accepted standard of care in the United States and many other countries.



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Sentinel node biopsy-in which the first, or sentinel, axillary lymph node to which breast tissue drains is sampled to determine if tumor cells have spread beyond the breast-is the subject of a new set of guidelines from the American Society of Clinical Oncology.

Used with permission by Mayo Foundation

 
Experts also agree that the swift adoption of SNB has outpaced efforts to answer the many questions surrounding it. "Here is a technique that is accepted and disseminated widely despite wide variability in performance and no long-term results from randomized controlled trials," said Gary Lyman, M.D., of the University of Rochester School of Medicine and Dentistry in Rochester, N.Y.



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Gary Lyman

 
Now, the American Society of Clinical Oncology has issued clinical practice guidelines for sentinel node biopsy in early-stage breast cancer in an attempt to address what the authors call the "complexities, limitations, and variability of SNB performance." Published in October in the Journal of Clinical Oncology, the guidelines emerged from a 2-year review by an expert panel, co-chaired by Lyman and Armando Giuliano, M.D., of the John Wayne Cancer Institute in Santa Monica, Calif. Also, for the first time, ASCO has prepared user-friendly materials for physicians and patients to accompany these guidelines and will be actively working to disseminate them.



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Armando Giuliano

 
Broadly speaking, the new guidelines support current practice. Eligible patients with negative SNBs need not have an initial full axillary lymph node dissection, and patients with positive SNBs should have the full procedure, according to the guidelines. However, ASCO recommends that surgeons maintain a low threshold for defaulting to axillary lymph node dissection when there is any uncertainty about the success of the procedure or the status of the remaining lymph nodes.

The panel acknowledges that there are insufficient data to answer the most important question about SNB—its effect on recurrence rates and survival. The answer to this awaits outcome data from B-32, a large, randomized trial led by the National Surgical Adjuvant Breast and Bowel Project, which may not be available for at least several years, according to principal investigator David Krag, M.D., of the University of Vermont College of Medicine in Burlington.

Performance Guidelines

Despite the lack of data on this important question, the ASCO panel did address other uncertainties and debates that have surrounded SNB, including how, by whom, and for whom SNB should be performed.

To approach these issues, the panel reviewed some 69 published reports on SNB, looking for factors associated with false-negative rates. It found that the proportion of false negatives—cases in which tumor cells were not found in the sentinel node but were found in other nodes—varied widely among hospitals and cancer centers, ranging from zero to almost 30%. The strongest predictor of the false-negative rate in an institution was the proportion of patients for whom surgeons were able to successfully locate and identify, or "map," the sentinel node.

Successful mapping was related to several factors, including the mapping techniques used. The two commonly used techniques both involve an injected substance that is tracked as it drains through the breast's lymphatic system to the axillary nodes. Which of the two techniques to use—a blue dye that is tracked visually or a radiolabeled colloid tracked by a handheld gamma camera—has been a subject of debate. The panel's meta-analysis suggested that using both together yielded the lowest false-negative rates and the highest proportions of successful mappings.

The guidelines, however, stop short of recommending that both be used. "The meta-analysis showed borderline statistical significance for using both," Lyman said, "but ... there was enough uncertainty that we did not make it a rigid recommendation."

"Some of the most successful surgeons in the world use only one of these methods," noted Giuliano, although "the novice is most likely to be successful using both."

Also associated with successful mapping and low false-negative rates is surgeon experience and training. On this issue, the panel emphasized the importance of experience but deferred to training standards set by the American Society of Breast Surgeons. These recommend that before surgeons start doing routine SNBs, they perform at least 20 SNB procedures in combination with full axillary dissection or with mentoring, establish a rate of SLN identification of at least 85%, and have a false-negative rate of no more than 5%.

Still another variable among institutions performing SNB has been the patients for whom it is used. ASCO does not recommend SNB for patients with tumors larger than 5 cm. However, the guidelines do approve SNB for women with more than one primary tumor, since recent studies have shown that the same sentinel node is "sentinel" for the entire breast.

Mapping the sentinel node may be more difficult in older or obese patients than in other breast cancer patients, but this should not be a contraindication for SNB, say the guidelines. SNB is not recommended for women with ductal carcinoma in situ who have breast-conserving surgery or for women with inflammatory breast cancer.

Micrometastases

One of the critical questions for clinicians is what to do about sentinel node micrometastases—tumors between 0.2 and 2 mm in diameter. These very small metastases often show up with sophisticated staining techniques in sentinel nodes that are negative by routine testing. But there are not enough data yet on what micrometastases mean, in terms of prognosis, to tell clinicians and patients what to do about them. "As a breast cancer specialist, this is a daily subject of discussion," said Lyman.

Data to inform this discussion will be coming from the NSABP's trial as well as another large study with more than 5,500 patients, led by the American College of Surgeons Oncology Group. Both studies are tracking outcomes in patients with sentinel node micrometastases, but in both cases it will be at least several years before data are available.

In the meantime, the ASCO panel has taken a conservative stance. Noting that metastasis is found in the nonsentinel nodes in 20%–35% of patients with sentinel node micrometastases, the guidelines recommend routine axillary lymph node dissection for patients with micrometastases.

Disseminating the Guidelines

The SNB guidelines join about 30 others on ASCO's Web site that, like other clinical recommendations, face the large hurdle of getting translated into daily practice.

"There's a whole body of literature showing dissemination and implementation of guidelines is a major roadblock," said Antonio Wolff, M.D., an oncologist at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore.

Wolff is a leader of a new initiative by ASCO to address this problem, beginning with the SNB guidelines. Launched in October by e-mail to members, the initiative includes a series of products called "Best Practice Tools," aimed at making the guidelines more accessible and user-friendly. There are plain English summaries for clinicians and patients and PowerPoint presentations that physicians could use, for instance, with hospital tumor boards. Treatment and prevention guidelines will be accompanied by flowsheets for patients' charts to help guide follow-up.

A related initiative will provide feedback on use of the guidelines, Wolff said. "We have to know whether guidelines are being used, to what degree, and if not, what is the problem."



             
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