What are the current indications for sentinel node biopsy, and how should enhanced pathology (such as IHC) be used in clinical decision-making?

OVERVIEW: A series of classic randomized trials — including NSABP B-04 — formed the basis for level 1 and 2 axillary node dissection becoming a standard of care for invasive breast cancer. The emergence of sentinel node biopsy (SNB) as an initial staging procedure has led to a new generation of trials evaluating the need for axillary dissection in women with both pathologically negative and positive SNB. In the United States, NSABP B-32 is evaluating the management of patients with negative sentinel node biopsies by randomization to either axillary node dissection or no further axillary surgery. While many investigators are convinced that the anatomic hypothesis of the sentinel node has been demonstrated, one important outcome of the NSABP trial will be to observe the accuracy and reproducibility of this procedure with many surgeons in various clinical settings. Another key U.S. sentinel node trial is being conducted by the American College of Surgeons. This groundbreaking study will evaluate whether axillary node dissection is necessary in sentinel node-positive patients treated with lumpectomy and breast irradiation. A key factor is whether the additional antitumor effect of adjuvant systemic therapy mitigates the need for axillary dissection in these women. In addition, another critical question addressed by trials of the American College of Surgeons is the interpretation of micrometastases in both the sentinel lymph node and the bone marrow. The clinical significance of these findings on enhanced pathology is a critical treatment issue, which becomes even more important as the use of sentinel node biopsy increases.

Is sentinel node biopsy generally a good option for the following women: YES A 56-year-old woman with a 2 cm breast cancer in the upper outer quadrant and a 1 cm breast cancer in the lower inner quadrant 46% A 42-year-old woman with a 3 cm breast cancer who wants mastectomy with immediate reconstruction using TRAM flap 60% A 55-year-old woman with a 2 cm breast cancer high in the upper outer quadrant in the tail of Spence 78% Is sentinel lymph node biopsy a standard of care for patients with clinical T1NO cancer? 70% Do you ever do axillary node dissection on an outpatient basis? 69%

NSABP B-04 TRIAL: A PROTOCOL FOR THE EVALUATION OF RADICAL MASTECTOMY VERSUS TOTAL MASTECTOMY WITH AND WITHOUT RADIATION IN THE PRIMARY TREATMENT OF BREAST CANCER CLOSED PROTOCOL

Fisher B et al. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Eng J Med 1985; 312:674-681. Abstract

“Our findings indicate that the location of a breast tumor does not influence the prognosis and that irradiation of internal mammary nodes in patients with inner-quadrant lesions does not improve survival. ... We conclude that the variations of local and regional treatment used in this study are not important in determining survival of patients with breast cancer.”

AMERICAN COLLEGE OF SURGEONS Z-10 TRIAL: A PHASE III PROGNOSTIC STUDY OF SENTINEL NODE AND BONE MARROW MICROMETASTASES IN WOMEN WITH STAGE I OR IIA BREAST CANCER PROTOCOL

All patients receive whole breast radiotherapy (exclusive of a supraclavicular field) 5 days a week for a maximum of 7 weeks and systemic adjuvant therapy. Patients with no sentinel node identified intraoperatively and patients with sentinel node metastasis identified by H & E who choose not to be registered to ACOSOG-Z0011 undergo ALND.

STUDY CONTACT Armando E Giuliano, Ph: 310-829-8089 John Wayne Cancer Institute Santa Monica, California

NSABP B-32 TRIAL: PHASE III RANDOMIZED STUDY OF SENTINEL NODE DISSECTION WITH OR WITHOUT CONVENTIONAL AXILLARY DISSECTION IN WOMEN WITH CLINICALLY NODE-NEGATIVE BREAST CANCER OPEN PROTOCOL

All patients receive technetium Tc 99m sulfur colloid injected into normal breast tissue within 1 cm of the primary tumor or biopsy cavity, approximately 0.5-8 hours before surgery. Patients also receive an injection of isosulfan blue dye around the tumor or biopsy cavity after a hot spot is identified with a gamma detector.

STUDY CONTACT: David N. Krag, Chair, Ph: 802-656-5830 National Surgical Adjuvant Breast and Bowel Project Pittsburgh, Pennsylvania

AMERICAN COLLEGE OF SURGEONS Z-11 TRIAL: A PHASE III RANDOMIZED STUDY OF AXILLARY LYMPH NODE DISSECTION IN WOMEN WITH STAGE I OR IIA BREAST CANCER WHO HAVE A POSITIVE SENTINEL NODE OPEN PROTOCOL

Patients in both arms may receive adjuvant systemic therapy at the discretion of the treating physician.

STUDY CONTACT Armando E Giuliano, Ph: 310-829-8089 John Wayne Cancer Institute Santa Monica, California

AXILLARY DISSECTION FOR SNB-POSITIVE PATIENTS

For 20 years, we have been hearing that axillary surgery is a staging procedure. However, once you have a positive node, the patient is staged, so does it make sense to subject her to the morbidity of an axillary dissection? I think the answer to that right now is, yes, for several reasons.

First, axillary dissection will maintain local control in the axilla in 98-99 percent of patients — whether they’re node-positive or node-negative. That’s very important because uncontrolled axillary disease is extremely difficult to treat and extremely morbid. Also, medical oncologists need to accurately estimate the risk of recurrence to educate patients about the risks and benefits of adjuvant therapy. To do that, in general, you need to know the number of positive nodes.

The therapeutic benefit of axillary dissection remains open. NSABP B-04 showed no survival benefit, but the trial was a premammography era study, so the patients had larger tumors, and no adjuvant therapy was being used at that time. Also, the sample size was not large enough to detect a small survival difference that today we would think is clinically relevant.

Currently, the standard management of a positive sentinel node is to complete the axillary dissection, although there are individual circumstances where that might not be appropriate. I’m proud to say that our center has the second-highest accrual to the American College of Surgeons trials — basically asking the same question as NSABP B-04 in a modern setting. Without these trials, we will still be asking this question 10 years from now and making random decisions.

—Monica Morrow, MD

ACCRUAL TO SENTINEL NODE TRIALS

In some ways sentinel node mapping is becoming a victim of its own success. As surgeons realize that it is not a terrific technical feat to learn, and as more patients become aware of it through the Internet and other sources, it will become harder and harder to find both patients and physicians willing to participate in these randomized clinical trials.

—Patrick Borgen, MD

CONTRIBUTION OF SURGEONS TO BREAST CANCER RESEARCH

Although other physicians are increasingly involved in the primary management of cancer, surgeons remain largely responsible for determining such care and deciding whether patients enter clinical trials. Surgeons have not only inaugurated the use of systemic adjuvant therapy and continue to be leaders in that effort, they have also redefined the basis for oncologic surgical operation and, in so doing, have contributed to a better understanding of the biology of cancer and, consequently, its treatment.

—Bernard Fisher, MD, News from the Commission on
Cancer of the American College of Surgeons 1991;2(2)

COMMENTS FROM SURGICAL RESEARCH LEADERS ON SENTINEL NODE TRIALS

There are three reasons to do axillary dissection: regional control, staging and to improve survival. For staging, we have enough literature from around the world to tell us the accuracy of sentinel node biopsy. For regional control, surgery results in almost 100% control, as does radiation therapy, so before we abandon something that works very well, we have to be very careful. We don't have any long-term data on regional control for sentinel node. Regarding the issue of survival — and I know it is a little heretical to say this — there may be a survival advantage in controlling the axilla. The few studies that looked at this were done in an era when we randomized hundreds of patients, not thousands of patients. So the statistical power was not there.

I've personally never done a sentinel node procedure in a breast cancer case outside of a clinical trial. I'm not going to say that it shouldn't be done — this is a judgment call. But in terms of making the claim that sentinel node is as good as axillary dissection, we don't have the data and we are in an era of evidence-based medicine.

—David Krag, MD

Many surgeons believe that axillary dissection is therapeutic, and they are reluctant not to perform axillary dissection in sentinel node-positive patients. However, a number of randomized studies failed to show that axillary dissection improves survival. In sentinel node-positive women, the sentinel node may be enough because often it's the only involved node.

Virtually all node-positive women in this country receive adjuvant systemic therapy, which may take care of any residual problem in the axilla. Many patients are also receiving opposed tangential field radiation, and that's partial axillary radiation.

In studies where patients received lumpectomy with radiation and no axillary dissection, the axillary recurrence rate was extraordinarily low. I think ACOS Z-11 is a very important, very justifiable and ethical trial. For an operation that's been used for 100 years, it's time to answer the question about the need for axillary dissection.

—Armando Giuliano, MD

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