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Editorial |
1 Department of Surgical Oncology, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston, Texas 77030
2 Department of Radiation Oncology, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
3 Department of Breast Medical Oncology, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
Correspondence: Address correspondence and reprint requests to: Kelly K. Hunt, MD, FACS; E-mail: khunt{at}mdanderson.org
The management of patients with breast cancer has shifted from a focus of primary locoregional control to a multidisciplinary treatment approach that includes local therapy, regional therapy, and systemic therapy. Identifying the appropriate treatment algorithm for each patient is based on the stage of disease at presentation and the ultimate goal of curing the patient of all disease. The optimal management of breast cancer requires the participation of individuals from many different fields and a clear understanding from all of our participating multidisciplinary specialists on how delivery of each treatment affects the others. Nothing exemplifies this better than the issue of lymph node management in patients receiving preoperative chemotherapy for breast cancer. Preoperative chemotherapy was initially introduced in the management of locally advanced breast cancer patients and was intended to treat occult metastases that were thought to be present at the time of diagnosis but were not demonstrable with available imaging studies. Preoperative chemotherapy converted some patients from inoperability to surgical candidacy. Indeed, the combination of surgery, chemotherapy, and radiotherapy converted a disease with a once-dismal prognosis to one that was potentially curable with this multidisciplinary approach.
Preoperative chemotherapy has been extended to the setting of operable breast cancer patients primarily to allow for a breast-conserving approach for patients who present with tumors that are too large to allow for a cosmetically acceptable lumpectomy. An additional benefit is the ability to assess the response of the primary tumor and any nodal metastases to the particular regimen used. Although guidelines have been suggested for the appropriate use of breast-conserving surgery after preoperative chemotherapy, there has been no such consensus regarding the management of the axilla in these patients. Axillary dissection has been routinely used after preoperative chemotherapy even though a major premise for the use of chemotherapy has been the possibility of less aggressive operative approaches. At the same time that surgeons have increasingly accepted the concept that it is safe to perform a lumpectomy (and often resect a smaller volume than the size of the presenting tumor mass in the breast) after chemotherapy, there has been a greater reluctance to adopt sentinel lymph node surgery as a less invasive approach to the axilla in the same patient.
The introduction of sentinel lymph node surgery in the management of early-stage breast cancer patients has allowed us to discriminate patients who harbor lymph node metastases from those who have disease limited to the breast. This has proven to be an accurate staging tool, in addition to selecting patients who require an axillary dissection for regional control. Because the major morbidity associated with breast cancer surgery is associated with the axillary dissection, it stands to reason that the procedure should be performed only in individuals whose risk-benefit ratio is favorable. The early experience with sentinel lymph node surgery after chemotherapy revealed relatively high false-negative rates, which ranged anywhere from 0% to 33%. The initial reports were hindered by small numbers of patients (n = 14–82).1 With such small sample sizes, it takes only a few events to result in a high false-negative rate. A more recent report from our institution and the results reported by investigators participating in the National Surgical Adjuvant Breast and Bowel Project B-27 trial have more patients and have false-negative rates comparable to those reported in large series of early-stage breast cancer patients treated with surgery first (false-negative rates of 7% and 9%, respectively).2,3
In this issue of Annals of Surgical Oncology, Khan et al.4 report their experience with using sentinel lymph node surgery in patients treated with preoperative chemotherapy, both before chemotherapy as a staging tool and after chemotherapy as a posttreatment assessment tool. They used ultrasonography of the axillary nodal basin with fine-needle aspiration biopsy to document the nodal status before chemotherapy or sentinel lymph node dissection in a group of 91 patients treated at the University of Michigan Comprehensive Cancer Center. They identified 53 patients (58% ) who were node negative before and after chemotherapy and 38 patients who were identified as having node-positive disease at presentation; 18 patients were identified by sentinel lymph node biopsy, and 20 were identified by ultrasound-guided fine-needle aspiration biopsy. Of the 38 patients with node-positive disease, 33 patients had a postchemotherapy sentinel lymph node biopsy followed by a completion axillary dissection. The procedure was successful in 32 patients, for an identification rate of 97%. Of the 32 successfully mapped patients, 22 (69% ) had residual disease identified in the axillary lymph nodes. There was only one case of a negative sentinel lymph node but a positive axillary lymph node, for a false-negative rate of 4.5%. The authors noted that repeat sentinel lymph node biopsy after chemotherapy was feasible in their patient population and was successful in 12 of 13 cases. A complete pathologic response to neoadjuvant chemotherapy was noted in 30% of the cases. The authors suggest that this now-and-later approach of sentinel node biopsy (at diagnosis and again after completion of chemotherapy) is a feasible and accurate means of identifying patients with residual axillary metastasis who require additional therapy.
The results of this study should cause us to consider what information we need to gain from the axillary contents and at what point in the patient’s treatment course we should perform a sentinel lymph node biopsy. National Institutes of Health consensus guidelines state that systemic chemotherapy should be considered for patients with invasive tumors >1 cm regardless of nodal status. There is, however, a lack of consensus regarding the appropriate regimen for an individual patient. Some clinicians use the status of the regional nodes to decide whether taxanes should be added to a doxorubicin-based regimen, and in this setting, a sentinel node biopsy before chemotherapy would be appropriate. Our approach at The University of Texas M. D. Anderson Cancer Center has been to use an anthracycline- and taxane-containing regimen for both node-negative and node-positive patients because we still cannot discriminate the subsets within these groups that harbor occult metastases and are therefore at highest risk.5
The next question is how we treat the axilla after chemotherapy. In the study by Khan et al.,4 which used a doxorubicin-based chemotherapy regimen, 70% of the patients who had node-positive disease at presentation still had pathologic evidence of disease at operation. This suggests that the likelihood of avoiding axillary surgery (by eradicating all evidence of disease) in this patient population is small, at least with the chemotherapy used in this study. Published studies with this patient population suggest that axillary dissection and axillary irradiation are equally effective at providing locoregional control in this patient population.6 Why, then, do we need to perform a sentinel node biopsy at all? Completing the axillary operation gives us an idea of the volume of disease that remains and the number of positive lymph nodes, but will this effect a change in management of the patient? Will this affect their outcomes or chances for long-term survival?
In addition to potentially affecting systemic treatment decisions, information gathered from axillary surgery also can influence locoregional treatment. Some patients with positive lymph nodes after chemotherapy benefit from irradiation of the supraclavicular fossa. However, such treatments increase the morbidity of radiation treatment and are unnecessary for patients with clinically negative lymph nodes who have negative sentinel lymph node biopsy results. Therefore, information gathered from the axillary operation, whether it be before or after chemotherapy, not only has the therapeutic benefit of removing foci of disease, but also can affect decisions concerning radiation field design or decisions about when to add postmastectomy radiation.7
It is important for the treating clinicians to determine at the outset what the goals of therapy are for each patient. For patients with tumor characteristics at baseline that indicate maximum therapy, i.e., an anthracycline- and taxane-containing regimen, there is no benefit from knowing the axillary contents for a clinically lymph node–negative patient before the initiation of therapy. The only benefit to knowing the axillary contents after chemotherapy would be the case in which this would alter radiation field design. For patients with small, clinically T1N0 invasive tumors, the axillary contents may contribute to the decision about adjuvant chemotherapy in some quarters: however, those patients are rarely offered preoperative chemotherapy. For patients with clinical stage III disease, radiotherapy should be performed at the completion of chemotherapy and operation regardless of the response to chemotherapy. That leaves patients with clinical stage II disease, who have a lower risk of recurrence. This is the patient population in which sentinel node biopsy could be used to obtain pathologic information after preoperative chemotherapy to make decisions regarding radiotherapy, and there would be no added value from performing a sentinel node biopsy before chemotherapy is initiated.
Therefore, although the article by Khan et al.4 indicates that sentinel node biopsy can be performed safely before and after chemotherapy, this does not need to be done routinely for the great majority of patients. It might be an interesting research tool, but does it provide any clinical benefit? Does it help physicians make decisions they could not otherwise make? If the goal is to perform lumpectomy after chemotherapy, then the patient should be offered all of her systemic therapy before operation to optimize this approach. The surgeon and radiation oncologist should consult before the initiation of treatment to assess the suitability of each patient for breast-conserving surgery and radiation.
Finally, as a note of caution, the status of the lymph nodes after chemotherapy may or may not be best evaluated with sentinel lymph node dissection for patients with node-positive disease at presentation. In our own experience at the M. D. Anderson Cancer Center, we found that patients who presented with node-positive disease documented by a fine-needle aspiration biopsy before chemotherapy had a higher-false negative rate with sentinel lymph node biopsy at the completion of their chemotherapy than patients who presented with clinically node-negative disease before treatment.8 As the current study shows, most patients who have node-positive disease at presentation will continue to have node involvement after preoperative chemotherapy, and, therefore, we have not gained much in using sentinel node biopsy in this patient population. The authors are to be congratulated for demonstrating the feasibility and accuracy of sentinel node biopsy before and after chemotherapy in this patient population; however, this approach will not alter decisions regarding therapy in most patients. We must search for improved systemic therapy regimens and improved imaging tools if we hope to limit the extent of our surgical approach. Future advances in molecular diagnostics and prognostics may help to determine which patients will have a complete response in the breast and regional nodes to a specific chemotherapy regimen. This could allow for a more clearly defined role for sentinel lymph node surgery in patients designated for preoperative chemotherapy.
Received for publication March 1, 2005. Accepted for publication March 25, 2005.
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